Supplementary Information Divergent ring-opening coupling between

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capillary column, DB-5 (Agilent J&W, 0.25 mm i.d. x 30 m, 0.25 µm film thickness). ..... 2.63-2.60 (m, 2H), 2.29-2.25 (m, 2H), 1.51-1.47 (m, 2H), 1.32 (q, J = 7.5 Hz, ...
Electronic Supplementary Material (ESI) for Chemical Science. This journal is © The Royal Society of Chemistry 2018

Supplementary Information Divergent ring-opening coupling between cyclopropanols and alkynes under cobalt catalysis Junfeng Yang, Yixiao Shen, Yang Jie Lim, and Naohiko Yoshikai* Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore

Contents

Materials and Methods ............................................................................................................. S2! Cobalt-Catalyzed Hydroalkylation Reaction between Cyclopropanols and Alkynes .............. S4! Cobalt-Catalyzed [3 + 2] Annulation Reaction between Cyclopropanols and Alkynes ........ S18! Preliminary Study on Enantioselective [3 + 2] Annulation ................................................... S28! Control Experiments .............................................................................................................. S34! Computational Studies ........................................................................................................... S43! References .............................................................................................................................. S66! NMR Spectra .......................................................................................................................... S68!

S1

Materials and Methods General. All reactions dealing with air- or moisture-sensitive compound were performed by standard Schlenk techniques in oven-dried reaction vessels under nitrogen atmosphere or in the argon-filled glove box. Analytical thin-layer chromatography (TLC) was performed on Merck 60 F254 silica gel plates. Flash chromatography was performed as described by Still et al., using 40–63 µm silica gel (Si 60, Merck). 1H and 13C nuclear magnetic resonance (NMR) spectra were recorded on Bruker AV-400 (400 MHz) NMR spectrometers. 1H and 13C NMR spectra are reported in parts per million (ppm) downfield from an internal standard, tetramethylsilane (0 ppm) and CHCl3 (77.1 ppm), respectively. Gas chromatographic (GC) analysis was performed on a Shimadzu GC-2010 system equipped with an FID detector and a capillary column, DB-5 (Agilent J&W, 0.25 mm i.d. x 30 m, 0.25 µm film thickness). Highresolution mass spectra (HRMS) were obtained with a Q-Tof Premier LC HR mass spectrometer. Melting points were determined using a capillary melting point apparatus and are uncorrected. Materials. Unless otherwise noted, commercial reagents were purchased from Aldrich, Alfa Aesar, and other commercial suppliers and were used as received. Manganese (-325 mesh, 99.95%) were purchased from Alfa Aesar and used without further activation. Zinc (-100 mesh, 97+%) was purchased from Alfa Aesar and was washed successively with 1 M HCl, diethyl ether, and acetone, dried under vacuum, and stored under argon. MeCN was distilled over CaH2 and stored under N2. Anhydrous CoCl2 (99.7%) was purchased from Aldrich. Anhydrous CoBr2 (99%) was purchased from Alfa Aesar. Anhydrous DMSO (Aldrich) and anhydrous DMF (Alfa Aesar) was used without further purification and stored under N2. Cyclopropanols 1a,1 1b,1 1c,1 1d,1 1e,1 1f,1 1g,2 1h,3 1i,4 1j,5 1k,1 1l,1 1m,1 1n,6 1o,7 and 1p8 were prepared according to the literature procedure (Figure S1). Alkynes 2e,9 2f,10 2g,9 2h,11 2i,12 2j,12 2k,13 2l,14 2m,15 2n,14 2o,16 2p,17 2q,18 2r,12 and 2s19 were prepared according to the literature procedure. 1-Decylcyclopropanol (1k) White solid; Rf 0.3 (hexane/EtOAc = 10/1); 1H NMR (400 MHz, CDCl3) δ 1.77 (brs, 1H), 1.58-1.48 (m, 3H), 1.30-1.27 (m, 15H), 0.90-0.86 (m, 3H), 0.74-0.71 (m, 2H), 0.45-0.42 (m, 2H);

13

C NMR (100 MHz, CDCl3): δ 55.9, 38.3, 31.9, 29.7 (overlap), 29.6 (overlap), 29.3,

25.9, 22.7, 14.1, 13.5; HRMS (ESI) Calcd for C13H27O [M + H]+ 199.2060, found 199.2064.

S2

OH

OMe OH

OH

OH

R R 1a (R = H) 1b (R = Me) 1c (R = OMe) 1d (R = F) 1e (R = Cl)

1f (R = OMe) 1g (R = CF3)

OH

OH

S

1h

OH

OH

Ph 1i

1j

OH

OH

OH Me

Ph

n-C10H21

H 1l

1k

Bu Bu

1n

1m

1o R

R

Ph

1p Me

R 2a

2b (R = Et) 2c (R = Me) 2d (R = Bu)

Bu

F

MeO

Et

2m

Me

OBn

2n Ph n-C6H13

Figure S1. Cyclopropanols and alkynes used in this study.

S3

Ph Ph

2s

2r

Ph

EtO2C

2o

S

Bu

2k

Ph

Et

Ph

2q

2i (R = OMe) 2j (R = CF3)

Me

Bu 2l

n-C6H13

Bu

2e (R = OMe) 2f (R = CO2Et) 2g (R = Ph) 2h (R = Cl)

2t

2p

Cobalt-Catalyzed Hydroalkylation Reaction between Cyclopropanols and Alkynes Table S1. Ligand Effect on the Addition of 1-Benzylcyclopropanol to 5-Decynea OH

Bu

+ Bn

Bu 1j

DABCO (150 mol %) DMSO, 80 °C, 12 h

2a

Bn 3j

yield (%)b

1

dppe

86

2

dppm

17

3

dppp

60

4

dpphex

15

5

dpephos

19

6



12

7c

dppe

89

n

Bu Bu

ligand

PPh2

dppm (n = 0) dppe (n = 1) dppp (n = 2) dpphex (n = 5)

b

O

entry

Ph2P

a

CoCl2 (10 mol %) ligand (10 mol %) Zn (50 mol %)

O Ph2P

PPh2 dpephos

The reaction was performed on using 0.15 mmol of 1j and 0.1 mmol of 2a (0.3 M).

Determined by GC using mesitylene as an internal standard. cCoBr2 was used instead of

CoCl2. General procedure: In an argon-filled glove box, a 4-mL vial equipped with a magnetic stirrer bar was charged sequentially with CoBr2 (6.5 mg, 0.030 mmol), dppe (12.0 mg, 0.030 mmol, for dialkylalkyne) or dpphex (13.6 mg, 0.030 mmol, for aryl(alkyl)alkyne or diarylalkyne), zinc powder (9.8 mg, 0.15 mmol), DABCO (50.4 mg, 0.45 mmol), cyclopropanol substrate (0.45 mmol), and alkyne (0.30 mmol), followed by the addition of DMSO (0.9 mL). The vial was closed and removed from the glove box, and the mixture was stirred at 80 °C for 24 h. Upon cooling to room temperature, the reaction mixture was diluted with ethyl acetate (3 mL) and filtered through a pad of silica gel with additional ethyl acetate (10 mL) as an eluent. The organic solution was concentrated under reduced pressure, and the residue was purified by flash chromatography on silica gel to afford the desired product.

S4

O Ph

Bu Bu

(E)-4-Butyl-1-phenylnon-4-en-1-one (3a) Light yellow oil (74 mg, 91%); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.97-7.95 (m, 2H), 7.57-7.54 (m, 1H), 7.48-7.44 (m, 2H), 5.16 (t, J = 7.1 Hz, 1H), 3.08-3.04 (m, 2H), 2.43-2.39 (m, 2H), 2.07-2.00 (m, 4H), 1.39-1.28 (m, 8H), 0.93-0.87 (m, 6H);

13

C

NMR (100 MHz, CDCl3) δ 200.3, 138.1, 137.1, 132.9, 128.6, 128.1, 125.5, 37.7, 32.3, 31.3, 30.7, 30.1, 27.4, 22.8, 22.4, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C19H29O [M + H]+ 273.2218, found 223.2230. The E-geometry of the double bond was confirmed by NOESY analysis. O Bu Bu

Me

(E)-4-Butyl-1-(p-tolyl)non-4-en-1-one (3b) Light yellow oil (81 mg, 99%); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 6.7 Hz, 2H), 5.15 (t, J = 7.1 Hz, 1H), 3.04-3.00 (m, 2H), 2.41 (s, 3H), 2.41-2.37 (m, 2H), 2.07-1.98 (m, 4H), 1.37-1.29 (m, 8H), 0.92-0.87 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 200.0, 143.6, 138.2, 134.6, 129.2, 128.2, 125.4, 37.6, 32.3, 31.4, 30.7, 30.1, 27.4, 22.8, 22.4, 21.6, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C20H31O [M + H]+ 287.2375, found 287.2374. O Bu MeO

Bu

(E)-4-Butyl-1-(4-methoxyphenyl)non-4-en-1-one (3c) Light yellow oil (78 mg, 86%); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.8 Hz, 2H), 5.15 (t, J = 7.1 Hz, 1H), 3.87 (s, 3H), 3.022.98 (m, 2H), 2.41-2.37 (m, 2H), 2.07-1.98 (m, 4H), 1.34-1.29 (m, 8H), 0.92-0.89 (m, 6H); 13

C NMR (100 MHz, CDCl3) δ 198.9, 163.3, 138.3, 130.3, 130.2, 125.4, 113.7, 55.4, 37.4,

32.3, 31.5, 30.7, 30.1, 27.4, 22.8, 22.4, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C20H31O2 [M + H]+ 303.2324, found 303.2315.

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O Bu Bu

F

(E)-4-Butyl-1-(4-fluorophenyl)non-4-en-1-one (3d) Light yellow oil (79 mg, 91%); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.99 (dd, J = 8.8, 5.5 Hz, 2H), 7.13 (t, J = 8.6 Hz, 2H), 5.15 (t, J = 7.1 Hz, 1H), 3.04-3.00 (m, 2H), 2.42-2.38 (m, 2H), 2.06-1.98 (m, 4H), 1.38-1.26 (m, 8H), 0.93-0.87 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 198.7, 165.6 (d, 1JC-F = 254.3 Hz), 138.0, 133.5 (d, 4JC-F = 3.1 Hz), 130.7 (d, 3JC-F = 9.0 Hz), 125.6, 115.6 (d, 2JC-F = 21.8 Hz), 37.6, 32.2, 31.3, 30.7, 30.1, 27.4, 22.8, 22.4, 14.03, 14.02; HRMS (ESI) Calcd for C19H28FO [M + H]+ 291.2124, found 291.2116. O Bu Bu

Cl

(E)-4-Butyl-1-(4-chlorophenyl)non-4-en-1-one (3e) Yellow oil (78 mg, containing 8% of 3aa as determined by 1H NMR, 78%); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.91-7.89 (m, 2H), 7.46-7.42 (m, 2H), 5.14 (t, J = 7.0 Hz, 1H), 3.06-3.00 (m, 2H), 2.41-2.39 (m, 2H), 2.06-1.98 (m, 4H), 1.36-1.27 (m, 8H), 0.93-0.87 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 199.0, 139.3, 137.9, 135.4, 129.5, 128.9, 125.7, 37.7, 32.2, 31.2, 30.7, 30.1, 27.4, 22.8, 22.4, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C19H28ClO [M + H]+ 307.1829, found 307.1811. O Bu Bu OMe

(E)-4-Butyl-1-(3-methoxyphenyl)non-4-en-1-one (3f) Yellow oil (77 mg, 85%); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 7.567.54 (m, 1H), 7.49-7.47 (m, 1H), 7.41-7.37 (m, 1H), 7.10 (dd, J = 8.2, 2.6 Hz, 1H), 5.15 (t, J = 7.2 Hz, 1H), 3.86 (s, 3H), 3.06-3.02 (m, 2H), 2.42-2.38 (m, 2H), 2.07-1.99 (m, 4H), 1.401.14 (m, 8H), 0.93-0.87 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 200.2, 159.8, 138.5, 138.1, 129.5, 125.5, 120.7, 119.3, 112.4, 55.4, 37.9, 32.3, 31.4, 30.7, 30.1, 27.4, 22.8, 22.4, 14.1 (two signals overlapped); HRMS (ESI) Calcd for C20H31O2 [M + H]+ 303.2324, found 303.2315. S6

O Bu Bu CF3

(E)-4-Butyl-1-(3-(trifluoromethyl)phenyl)non-4-en-1-one (3g) Light yellow oil (52 mg, 51%); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 8.14 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H), 5.15 (t, J = 7.8 Hz, 1H), 3.10-3.06 (m, 2H), 2.44-2.40 (m, 2H), 2.07-1.99 (m, 4H), 1.38-1.25 (m, 8H), 0.93-0.85 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 198.9, 137.8, 137.7, 131.3 (q, 2JC-F = 33.4 Hz), 131.2, 129.4, 129.3, 126.0, 125.0 (q, 3JC-F = 3.8 Hz), 124.2 (q, 1JC-F = 271.0 Hz), 37.9, 32.3, 31.2, 30.8, 30.1, 27.5, 22.9, 22.5, 14.1, 14.0; HRMS (ESI) Calcd for C20H28F3O [M + H]+ 341.2092, found 341.2094. O Bu OMe

Bu

(E)-4-Butyl-1-(2-methoxyphenyl)non-4-en-1-one (3h) Yellow oil (79 mg, 87%); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, J = 7.6, 1.7 Hz, 1H), 7.46-7.42 (m, 1H), 7.01-6.94 (m, 2H), 5.11 (t, J = 7.1 Hz, 1H), 3.90 (s, 3H), 3.07-3.03 (m, 2H), 2.37-2.33 (m, 2H), 2.04-1.97 (m, 4H), 1.36-1.27 (m, 8H), 0.920.87 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 203.0, 158.3, 138.4, 133.1, 130.2, 128.8, 125.2, 120.6, 111.4, 55.5, 42.8, 32.3, 31.5, 30.7, 30.1, 27.4, 22.8, 22.4, 14.1, 14.0; HRMS (ESI) Calcd for C20H31O2 [M + H]+ 303.2324, found 303.2325. O S

Bu Bu

(E)-4-Butyl-1-(thiophen-2-yl)non-4-en-1-one (3i) Dark yellow oil (62 mg, 74%); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 7.71 (dd, J = 3.8, 0.9 Hz, 1H), 7.62 (dd, J = 4.9, 0.8 Hz, 1H), 7.12 (dd, J = 4.8, 3.9 Hz, 1H), 5.16 (t, J = 7.2 Hz, 1H), 3.00-2.96 (m, 2H), 2.43-2.39 (m, 2H), 2.06-1.98 (m, 4H), 1.38-1.26 (m, 8H), 0.92-0.86 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 193.2, 144.5, 137.9, 133.3, 131.7, 128.0, 125.7, 38.6, 32.2, 31.7, 30.7, 30.0, 27.4, 22.8, 22.4, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C17H26OS [M + H]+ 279.1783, found 279.1791. Note that the

S7

presence of unidentified and inseparable impurities was indicated by minor peaks in the aromatic and aliphatic regions of the 1H NMR spectrum. O Bn

Bu Bu

(E)-5-Butyl-1-phenyldec-5-en-2-one (3j) Light yellow oil (74 mg, 86%); Rf 0.4 (hexane/EtOAc = 25/1);1H NMR (400 MHz, CDCl3) δ 7.41-7.19 (m, 5H), 5.04 (t, J = 7.1 Hz, 1H), 3.69 (s, 2H), 2.56-2.52 (m, 2H), 2.24-2.21 (m, 2H), 2.00-1.92 (m, 4H), 1.29-1.26 (m, 8H), 0.90-0.87 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 199.0, 163.3, 138.3, 130.3, 130.2, 125.4, 113.7, 55.4, 37.4, 32.3, 31.5, 30.7, 30.1, 27.4, 22.8, 22.4, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C20H31O [M + H]+ 327.2688, found 327.2683. O Bu

n-C10H21 Bu

(E)-6-Butylnonadec-5-en-9-one (3k) Colourless oil (67 mg, 69%); Rf 0.4 (hexane/EtOAc = 25/1);1H NMR (400 MHz, CDCl3) δ 5.07 (t, J = 7.1 Hz, 1H), 2.49-2.45 (m, 2H), 2.40-2.36 (m, 2H), 2.24-2.21 (m, 2H), 1.98-1.96 (m, 4H), 1.56-1.54 (m, 2H), 1.29-1.25 (m, 22H), 0.90-0.85 (m, 9H);

13

C NMR (100 MHz,

CDCl3) δ 211.3, 138.0, 125.3, 42.9, 41.7, 32.2, 31.9, 30.8, 30.7, 30.0, 29.6, 29.5, 29.4, 29.3, 29.3, 27.4, 23.9, 22.8, 22.7, 22.4, 14.1, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C23H45O [M + H]+ 337.3470, found 337.3466. O Bu Bu

(E)-4-Butyl-1-cyclohexylnon-4-en-1-one (3l) Yellow oil (70 mg, 84%); Rf 0.4 (hexane/EtOAc = 25/1);1H NMR (400 MHz, CDCl3) δ 5.08 (t, J = 7.1 Hz, 1H), 2.53-2.50 (m, 2H), 2.35-2.34 (m, 1H), 2.24-2.20 (m, 2H), 2.01-1.95 (m, 4H), 1.84-1.77 (m, 4H), 1.68-1.66 (m, 1H), 1.37-1.21 (m, 13H), 0.92-0.87 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 214.1, 138.2, 125.1, 50.9, 39.6, 32.3, 30.7, 30.6, 30.1, 28.5, 27.4, 25.9, 25.7, 22.8, 22.4, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C19H35O [M + H]+

S8

279.2688, found 279.2678. O Bu Bu

(E)-4-Butyl-1-cyclopropylnon-4-en-1-one (3m) Light yellow oil (50 mg, 71%); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 5.11 (t, J = 7.1 Hz, 1H), 2.65-2.62 (m, 2H), 2.30-2.26 (m, 2H), 2.02-1.92 (m, 5H), 1.36-1.28 (m, 8H), 1.03-0.99 (m, 2H), 0.92-0.84 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 210.9, 138.0, 125.3, 42.5, 32.2, 31.0, 30.7, 30.0, 27.4, 22.8, 22.4, 20.4, 14.0 (two signals overlapped), 10.6; HRMS (ESI) Calcd for C16H29O [M + H]+ 237.2218, found 237.2237. O Bu Bu

(E)-4-Butyl-1-(1,2,3,4-tetrahydronaphthalen-2-yl)non-4-en-1-one (3n) Yellow oil (80 mg, 89%); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.6 7.8 Hz, 1H), 7.45 (td, J = 7.5, 1.3 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 7.6 Hz, 1H), 5.16 (t, J = 7.1 Hz, 1H), 3.02-2.84 (m, 3H), 2.61-2.56 (m, 1H), 2.22-2.10 (m, 2H), 2.05-2.03 (m, 2H), 1.96-1.88 (m, 2H), 1.77-1.73 (m, 1H), 1.47-1.32 (m, 8H), 0.93-0.89 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 200.4, 144.1, 136.5, 133.1, 132.6, 128.7, 127.9, 127.5, 126.5, 45.5, 36.8, 32.3, 30.7, 29.2, 28.2, 27.5, 27.4, 22.9, 22.4, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C21H31O [M + H]+ 299.2375, found 299.2383. The structure of this compound, arising from cleavage of the less substituted C–C bond, was further confirmed by HMQC and HMBC analysis. O Bu

Me

Bu

(E)-4-Butyl-2-methyl-1-phenylnon-4-en-1-one (3o) The reaction was performed under modified conditions using CoBr2 (20 mol%), dppb (20 mol%), Zn (50 mol%), and DABCO (150 mol%) in MeCN (1 M) at 80 °C for 12 h. Colorless oil (46 mg, 54%); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.96-7.93 (m, 2H), 7.57-7.53 (m, 1H), 7.48-7.44 (m, 2H), 5.13 (t, J = 7.1 Hz, 1H), 3.65-3.60 (m, 1H), 2.53

S9

(dd, J = 13.8, 5.8 Hz, 1H), 2.09-1.91 (m, 5H), 1.35-1.21 (m, 8H), 1.16 (d, J = 6.8 Hz, 3H), 0.92-0.83 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 204.4, 136.9, 136.4, 132.7, 128.6, 128.2, 127.6, 40.7, 39.1, 32.1, 30.7, 29.8, 27.4, 22.8, 22.3, 17.0, 14.0 (two signals overlapped); HRMS (ESI) Calcd for C20H31O [M + H]+ 287.2375, found 287.2382. The structure of this compound, arising from cleavage of the less substituted C–C bond, was further confirmed by HMQC and HMBC analysis.

S10

Table S2. Ligand Effect on the Addition of 1-Phenylcyclopropanol (1a) to 1-Phenyl-1propyne (2b)a OH

CoBr2 (10 mol %) ligand (10 mol %) Zn (50 mol %)

Ph

+ Ph

Et 1a

DABCO (150 mol %) DMSO, 80 °C, 12 h

2b

O Ph

Ph Et 3p

entry

ligand

yield (%)b

regioselectivityc

1

dppm

67

6.3:1

2

dppe

86

4.4:1

3

dppp

66

5.8:1

4

dppb

50

4.2:1

5

dpppent

73

6.7:1

6

dpphex

76

9.0:1

7

dpephos

74

5.8:1

8

dppf

68

4.6:1

9

dppbz

29

6.1:1

11

dcype

--

--

Ph2P

n

PPh2

PPh2

dppm (n = 0) dppe (n = 1) dppp (n = 2) dppb (n = 3) dpppent (n = 4) dpphex (n = 5)

Fe

O Ph2P

PPh2

PPh2 dpephos

dppf

Cy2P Ph2P

PPh2 dppf

PCy2

dcype

a

The reaction was performed on using 0.15 mmol of 1j and 0.1 mmol of 2a (0.3 M).

b

Determined by GC using mesitylene as an internal standard. cDetermined by 1H NMR. O

Ph

Ph Et

(E)-4-Benzylidene-1-phenylhexan-1-one (3p) Yellow oil (65 mg, 82%, regioisomer ratio = 9:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.01-7.99 (m, 2H), 7.59-7.55 (m, 1H), 7.49-7.46 (m, 2H), 7.33-7.29 (m, 2H), 7.21-7.18 (m, 3H), 6.30 (s, 1H), 3.22-3.18 (m, 2H), 2.65-2.60 (m, 2H), 2.30 (q, J = 7.5 Hz, 2H), 1.12 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz,

S11

CDCl3) δ 199.9, 143.6, 138.2, 137.0, 133.1, 128.7, 128.6, 128.1, 128.1, 126.1, 125.0, 37.5, 31.0, 24.0, 13.1; HRMS (ESI) Calcd for C19H21O [M + H]+ 265.1592, found 265.1585. O Ph

Ph Me

(E)-4-Methyl-1,5-diphenylpent-4-en-1-one (3q) Light yellow solid (70 mg, 93%, regioisomer ratio = 9:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); m.p. 71-73 °C; 1H NMR (400 MHz, CDCl3) δ 8.00-7.98 (m, 2H), 7.57-7.55 (m, 1H), 7.49-7.46 (m, 2H), 7.33-7.29 (m, 2H), 7.25-7.19 (m, 3H), 6.33 (s, 1H), 3.22-3.18 (m, 2H), 2.64-2.60 (m, 2H), 1.91 (d, J = 1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.8, 138.2, 137.7, 137.0, 133.1, 128.8, 128.7, 128.1, 128.06, 126.1, 125.5, 37.4, 35.0, 18.0; HRMS (ESI) Calcd for C18H19O [M + H]+ 251.1436, found 251.1430. The E-geometry was confirmed by NOESY analysis. O Ph

Ph Bu

(E)-4-Benzylidene-1-phenyloctan-1-one (3r) Yellow oil (62 mg, 71%, regioisomer ratio = 7:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.01-7.99 (m, 2H), 7.57-7.55 (m, 1H), 7.50-7.46 (m, 2H), 7.33-7.29 (m, 2H), 7.21-7.18 (m, 3H), 6.32 (s, 1H), 3.22-3.18 (m, 2H), 2.63-2.60 (m, 2H), 2.29-2.25 (m, 2H), 1.51-1.47 (m, 2H), 1.32 (q, J = 7.5 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.9, 142.4, 138.3, 137.0, 133.0, 133.8, 128.6, 128.6, 128.1, 126.1, 125.4, 37.6, 31.5, 30.7, 30.6, 22.9, 13.9; HRMS (ESI) Calcd for C21H25O [M + H]+ 293.1905, found 293.1920. O Ph Bu

OMe

(E)-4-(4-Methoxybenzylidene)-1-phenyloctan-1-one (3s) Light yellow oil (53 mg, 55%, regioisomer ratio = 8:1 as determined by 1H NMR); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 8.00-7.99 (m, 2H), 7.59-7.55 (m, 1H), 7.50-7.46 (m, 2H), 7.13-7.11 (m, 2H), 6.86-6.84 (m, 2H), 6.25 (s, 1H), 3.81 (s, 3H), 3.20-3.16

S12

(m, 2H), 2.61-2.57 (m, 2H), 2.28-2.24 (m, 2H), 1.50-1.47 (m, 2H), 1.33 (q, J = 7.3 Hz, 2H), 0.89 (t, J = 7.2 Hz, 3H);

13

C NMR (100 MHz, CDCl3) δ 200.0, 157.9, 141.0, 137.0, 133.0,

130.8, 129.7, 128.6, 128.0, 124.9, 113.5, 55.2, 37.7, 31.6, 30.7, 30.6, 22.9, 14.0; HRMS (ESI) Calcd for C22H27O2 [M + H]+ 323.2011, found 323.2022. O Ph Bu

CO2Et

(E)-4-(4-Ethoxycarbonyl)-1-phenyloctan-1-one (3t) Light yellow oil (67 mg, 61%, regioisomer ratio = 14:1 as determined by 1H NMR); Rf 0.2 (hexane/EtOAc = 10/1); 1H NMR (400 MHz, CDCl3) δ 8.01-7.98 (m, 4H), 7.60-7.56 (m, 1H), 7.50-7.46 (m, 2H), 7.26-7.24 (m, 2H), 6.33 (s, 1H), 4.37 (q, J = 7.1 Hz, 2H), 3.23-3.19 (m, 2H), 2.66-2.62 (m, 2H), 2.29-2.25 (m, 2H), 1.52-1.48 (m, 2H), 1.39 (t, J = 7.2 Hz, 3H), 1.32 (q, J = 7.4 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.6, 166.6, 144.6, 143.0, 137.0, 133.1, 129.4, 128.7, 128.5, 128.1, 128.0, 124.8, 60.8, 37.4, 31.3, 30.9, 30.5, 22.8, 14.4, 13.9; HRMS (ESI) Calcd for C24H28O3 [M + H]+ 365.2117, found 365.2109. O Ph Bu

Ph

(E)-4-([1,1'-Biphenyl]-4-ylmethylene)-1-phenyloctan-1-one (3u) Yellow oil (88 mg, 80%, regioisomer ratio = 8:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.02-8.00 (m, 2H), 7.62-7.55 (m, 5H), 7.50-7.41 (m, 5H), 7.35-7.31 (m, 1H), 7.28-7.25 (m, 1H), 6.34 (s, 1H), 3.23-3.19 (m, 2H), 2.66-2.62 (m, 2H), 2.35-2.31 (m, 2H), 1.57-1.49 (m, 2H), 1.36 (q, J = 7.5 Hz, 2H), 0.91 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.9, 142.8, 140.9, 138.8, 137.3, 137.0, 133.1, 129.1, 128.8, 128.7, 128.1, 127.1, 126.9, 126.8, 125.0, 37.6, 31.6, 30.9, 30.6, 22.9, 14.0; HRMS (ESI) Calcd for C27H29O [M + H]+ 369.2218, found 369.2222. O Ph Bu

Cl

(E)-4-(4-Chlorobenzylidene)-1-phenyloctan-1-one (3v) Yellow oil (74 mg, 76%, regioisomer ratio = 11:1 as determined by 1H NMR); Rf 0.4 S13

(hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.00-7.98 (m, 2H), 7.59-7.56 (m, 1H), 7.50-7.46 (m, 2H), 7.28-7.26 (m, 2H), 7.11-7.09 (m, 2H), 6.25 (s, 1H), 3.20-3.17 (m, 2H), 2.63-2.59 (m, 2H), 2.25-2.21 (m, 2H), 1.49-1.45 (m, 2H), 1.31 (q, J = 7.3 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.68, 143.22, 136.98, 136.68, 133.08, 131.9, 129.94, 128.66, 128.23, 128.07, 124.28, 37.41, 31.39, 30.71, 30.45, 22.81, 13.92; HRMS (ESI) Calcd for C21H24ClO [M + H]+ 327.1516, found 327.1503. O Ph Bu CF3

(E)-1-Phenyl-4-(3-(trifluoromethyl)benzylidene)octan-1-one (3w) Light yellow oil (70 mg, 65%, regioisomer ratio = 17:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.01-7.99 (m, 2H), 7.60-7.56 (m, 1H), 7.50-7.46 (m, 2H), 7.43-7.30 (m, 4H), 6.32 (s, 1H), 3.23-3.19 (m, 2H), 2.65-2.62 (m, 2H), 2.26-2.22 (m, 2H), 1.52-1.46 (m, 2H), 1.32 (q, J = 7.4 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.6, 144.3, 138.9, 137.0, 133.1, 131.9, 130.5 (d, 2JC-F = 31.9 Hz), 128.7, 128.5, 128.1, 125.3 (q, 3JC-F = 3.8 Hz), 124.2 (q, 1JC-F = 270.5 Hz), 124.1, 122.8 (q, 3

JC-F = 3.8 Hz), 37.3, 31.4, 30.8, 30.5, 22.7, 13.8; HRMS (ESI) Calcd for C22H24F3O [M +

H]+ 361.1779, found 361.1800. Me

O Ph C6H13

(E)-4-(2-Methylbenzylidene)-1-phenyldecan-1-one (3x) Yellow oil (57 mg, 57%, regioisomer ratio = 3:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.01-7.99 (m, 2H), 7.57-7.55 (m, 1H), 7.50-7.46 (m, 2H), 7.16-7.06 (m, 4H), 6.24 (s, 1H), 3.22-3.19 (m, 2H), 2.65-2.61 (m, 2H), 2.18 (s, 3H), 2.12-2.08 (m, 2H), 1.43-1.37 (m, 2H), 1.25-1.16 (m, 6H), 0.83 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.93, 141.70, 137.61, 137.08, 136.33, 133.02, 129.60, 129.14, 128.64, 128.10, 126.46, 125.30, 124.74, 37.51, 31.59, 30.77, 30.71, 29.17, 28.07, 22.59, 19.94, 14.05; HRMS (ESI) Calcd for C24H31O [M + H]+ 335.2375, found 335.2369.

S14

O

OMe

Ph Et

(E)-4-(2-Methoxybenzylidene)-1-phenyloctan-1-one (3y) Yellow oil (45 mg, 51%, regioisomer ratio = 6:1 as determined by 1H NMR); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.5 Hz, 2H), 7.56-7.51 (m, 1H), 7.48-7.45 (m, 2H), 7.24-7.15 (m, 2H), 6.91 (t, J = 7.4 Hz, 1H), 6.85 (d, J = 8.2 Hz, 1H), 6.33 (s, 1H), 3.79 (s, 3H), 3.24-3.20 (m, 2H), 2.67-2.63 (m, 2H), 2.26 (q, J = 7.5 Hz, 2H), 1.09 (t, J = 7.6 Hz, 3H);

13

C NMR (100 MHz, CDCl3) δ 200.0, 157.1, 143.2, 137.1, 133.0,

130.0, 128.6, 128.1, 127.7, 127.1, 120.5, 120.1, 110.4, 55.4, 37.6, 30.6, 24.3, 13.1; HRMS (ESI) Calcd for C22H27O2 [M + H]+ 323.2011, found 323.2032. Me

O Ph Et

Me

(E)-4-(2,6-Dimethylbenzylidene)-1-phenylhexan-1-one (3z) Light yellow oil (44 mg, 50%, regioisomer ratio = 9:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.6 Hz, 2H), 7.59-7.55 (m, 1H), 7.50-7.46 (m, 2H), 7.06-7.00 (m, 3H), 6.04 (s, 1H), 3.24-3.21 (m, 2H), 2.69-2.65 (m, 2H), 2.15 (s, 6H), 1.88 (q, J = 7.6 Hz, 2H), 0.90 (t, J = 7.6 Hz, 3H);

13

C NMR (100 MHz,

CDCl3) δ 199.9, 142.8, 137.4, 137.1, 136.3, 133.0, 128.7, 128.1, 127.0, 126.3, 122.9, 37.3, 29.6, 24.1, 20.4, 12.2; HRMS (ESI) Calcd for C21H25O [M + H]+ 293.1905, found 293.1924. O Ph

Ph BnO

(Z)-4-((Benzyloxy)methyl)-1,5-diphenylpent-4-en-1-one (3aa) Light yellow oil (68 mg, 64%); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 7.99-7.97 (m, 2H), 7.58-7.54 (m, 1H), 7.47-7.43 (m, 2H), 7.32-7.19 (m, 10H), 6.59 (s, 1H), 4.47 (s, 2H), 4.19 (s, 2H), 3.28-3.24 (m, 2H), 2.80-2.76 (m, 2H);

13

C NMR (100 MHz,

CDCl3) δ 199.83, 138.13, 138.10, 137.01, 136.98, 132.97, 129.99, 128.82, 128.59, 128.39, 128.16, 128.13, 128.01, 127.69, 126.79, 72.63, 68.41, 37.72, 30.98; HRMS (ESI) Calcd for C25H25O2 [M + H]+ 357.1855, found 357.1851.

S15

O Ph EtO2C

Ph

Ethyl (Z)-4-benzylidene-7-oxo-7-phenylheptanoate (3ab) Colourless oil (60 mg, 60%, regioisomer ratio = 5:1 as determined by 1H NMR); Rf 0.2 (hexane/EtOAc = 10/1); 1H NMR (400 MHz, CDCl3) δ 8.01-7.98 (m, 2H), 7.59-7.56 (m, 1H), 7.50-7.46 (m, 2H), 7.34-7.30 (m, 2H), 7.23-7.15 (m, 3H), 6.38 (s, 1H), 4.13-4.07 (m, 2H), 3.23-3.20 (m, 2H), 2.65-2.60 (m, 4H), 2.50-2.46 (m, 2H), 1.22 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.47, 173.01, 139.86, 137.62, 136.97, 133.09, 128.66, 128.54, 128.27, 128.07, 127.02, 126.44, 60.48, 37.32, 33.02, 31.05, 26.26, 14.19; HRMS (ESI) Calcd for C22H25O3 [M + H]+ 337.1804, found 337.1812. O Ph

Ph

(Z)-4-Cyclopropyl-1,5-diphenylpent-4-en-1-one (3ac) Yellow oil (77 mg, 93%, regioisomer ratio = 3:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 8.01-7.99 (m, 2H), 7.59-7.55 (m, 1H), 7.52-7.46 (m, 2H), 7.40-7.38 (m, 2H), 7.34-7.29 (m, 2H), 7.20-7.17 (m, 1H), 6.38 (s, 1H), 3.22-3.19 (m, 2H), 2.36-2.33 (m, 2H), 1.86-1.82 (m, 1H), 0.77-0.73 (m, 2H), 0.59-0.55 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 199.7, 141.3, 138.0, 137.0, 133.1, 129.1, 128.6, 128.1, 127.9, 126.5, 126.0, 38.3, 28.3, 13.1, 7.4; HRMS (ESI) Calcd for C20H21O [M + H]+ 277.1592, found 277.1583. O S

Ph Bu

(E)-1-Phenyl-4-(thiophen-2-ylmethylene)octan-1-one (3ad) Yellow oil (79 mg, 88%, regioisomer ratio = 11:1 as determined by 1H NMR); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 8.00-7.97 (m, 2H), 7.59-7.55 (m, 1H), 7.50-7.46 (m, 2H), 7.19 (d, J = 5.1 Hz, 1H), 6.98 (dd, J = 5.0, 3.5 Hz, 1H), 6.90 (d, J = 3.5 Hz, 1H), 6.42 (s, 1H), 3.20-3.16 (m, 2H), 2.63-2.59 (m, 2H), 2.45-2.41 (m, 2H), 1.53-1.49 (m, 2H), 1.45-1.40 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 199.6, 141.7, 140.7, 137.0, 133.1, 128.7, 128.1, 126.7, 126.4, 124.1, 118.5, 37.6, 32.3, 32.0, 30.1, 23.1, S16

14.0; HRMS (ESI) Calcd for C19H23OS [M + H]+ 299.1470, found 299.1480. O Ph

Ph C6H13

(E)-1-Phenyl-4-((E)-3-phenylallylidene)decan-1-one (3ae) Yellow oil (82 mg, 79%, regioisomer ratio = 11:1 as determined by 1H NMR); Rf 0.4 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.99-7.96 (m, 2H), 7.58-7.54 (m, 1H), 7.49-7.42 (m, 2H), 7.40-7.38 (m, 2H), 7.32-7.28 (m, 2H), 7.21-7.17 (m, 1H), 7.01 (dd, J = 15.5, 11.0 Hz, 1H), 6.47 (d, J = 15.5 Hz, 2H), 6.05 (d, J = 11.0 Hz, 1H), 3.14 (t, J = 7.6 Hz, 2H), 2.56 (t, J = 7.5 Hz, 2H), 2.31 (t, J = 7.5 Hz, 2H), 1.50-1.45 (m, 2H), 1.39-1.31 (m, 6H), 0.91-0.88 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 199.7, 143.4, 138.0, 137.0, 133.1, 130.7, 128.6, 128.6, 128.1, 127.1, 126.2, 125.5, 125.2, 37.5, 31.8, 31.6, 31.3, 29.4, 28.9, 22.7, 14.1; HRMS (ESI) Calcd for C25H31O [M + H]+ 347.2375, found 347.2382. O Ph

Ph Ph

(Z)-1,4,5-Triphenylpent-4-en-1-one (3af) White solid (82 mg, 88%); Rf 0.4 (hexane/EtOAc = 25/1); m.p. 83-84 °C; 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 7.4 Hz, 2H), 7.55-7.51 (m, 1H), 7.44-7.40 (m, 2H), 7.32-7.24 (m, 4H), 7.20-7.18 (m, 2H), 7.11-7.05 (m, 2H), 6.93-6.91 (m, 2H), 6.53 (s, 1H), 3.08-3.04 (m, 2H), 2.98-2.93 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 199.6, 141.7, 140.5, 137.1, 136.9, 133.0, 132.6, 129.1, 128.7, 128.6, 128.0, 127.9, 127.2, 127.1, 126.3, 37.2, 35.1; HRMS (ESI) Calcd for C23H21O [M + H]+ 313.1592, found 313.1584.

S17

Cobalt-Catalyzed [3 + 2] Annulation Reaction between Cyclopropanols and Alkynes General procedure: In an argon-filled glove box, a 4-mL vial equipped with a magnetic stirrer bar was charged sequentially with CoI2 (9.3 mg, 0.030 mmol), dppe (12.0 mg, 0.030 mmol, for dialkylalkyne) or dppp (12.3 mg, 0.030 mmol, for aryl(alkyl)alkyne or diarylalkyne), zinc powder (9.8 mg, 0.15 mmol), DABCO (50.4 mg, 0.45 mmol, for dialkylalkyne or 16.8 mg, 0.15 mmol for aryl(alkyl)alkyne or diarylalkyne), cyclopropanol substrate (0.45 mmol), and alkyne (0.30 mmol), followed by the addition of MeCN (0.9 mL for dialkylalkyne or 3.0 mL for aryl(alkyl)alkyne or diarylalkyne). The vial was closed and removed from the glove box, and the mixture was stirred at 80 °C for 12 h. Upon cooling to room temperature, the reaction mixture was diluted with ethyl acetate (3 mL) and filtered through a pad of silica gel with additional ethyl acetate (10 mL) as an eluent. The organic solution was concentrated under reduced pressure, and the residue was purified by flash chromatography on silica gel to afford the desired product. Ph OH Bu Bu

2,3-Dibutyl-1-phenylcyclopent-2-enol (4a) Light yellow oil (68 mg, 83%); Rf 0.3 (hexane/EtOAc = 30/1); 1H NMR (400 MHz, CDCl3) δ 7.37-7.36 (m, 2H), 7.32-7.29 (m, 2H), 7.22-7.19 (m, 1H), 2.50-2.44 (m, 1H), 2.37-2.28 (m, 2H), 2.20-2.10 (m, 3H), 2.05-2.01 (m, 1H), 1.80-1.70 (m, 2H), 1.48-1.43 (m, 2H), 1.38-1.34 (m, 2H), 1.25-1.15 (m, 3H), 1.08-1.03 (m, 1H), 0.95 (t, J = 7.2 Hz, 3H), 0.77 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 147.0, 141.5, 140.2, 128.0, 126.3, 125.1, 89.8, 42.8, 32.4, 32.3, 30.3, 28.9, 25.2, 23.2, 22.9, 14.1, 13.8; HRMS (ESI) Calcd for C19H29O [M + H]+ 273.2218, found 273.2204. Me

OH Bu Bu

2,3-Dibutyl-1-(p-tolyl)cyclopent-2-enol (4b) Light yellow oil (69 mg, 80%); Rf 0.3 (hexane/EtOAc = 30/1); 1H NMR (400 MHz, CDCl3) δ

S18

7.25-7.23 (m, 2H), 7.13-7.11 (m, 2H), 2.49-2.42 (m, 1H), 2.37-1.98 (m, 9H), 1.77-1.71 (m, 2H), 1.49-1.33 (m, 4H), 1.29-1.08 (m, 4H), 0.94 (t, J = 7.2 Hz, 3H), 0.78 (t, J = 7.1 Hz, 3H); 13

C NMR (100 MHz, CDCl3) δ 144.1, 141.3, 140.2, 135.8, 128.7, 125.0, 89.8, 42.8, 32.4,

32.3, 30.3, 28.9, 25.2, 23.2, 22.9, 21.0, 14.1, 13.8; HRMS (ESI) Calcd for C20H31O [M + H]+ 287.2375, found 287.2388. F

OH Bu Bu

2,3-Dibutyl-1-(4-fluorophenyl)cyclopent-2-enol (4d) Light yellow oil (71 mg, 82%); Rf 0.3 (hexane/EtOAc = 30/1); 1H NMR (400 MHz, CDCl3) δ 7.34-7.31 (m, 2H), 7.00-6.96 (m, 2H), 2.50-2.43 (m, 1H), 2.38-2.07 (m, 5H), 2.04-1.96 (m, 1H), 1.75-1.70 (m, 2H), 1.49-1.33 (m, 4H), 1.26-1.04 (m, 4H), 0.95 (t, J = 7.2 Hz, 3H), 0.78 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 161.5 (d, 1JC-F = 254.3 Hz), 142.7 (d, 4JC-F = 2.9 Hz), 141.7, 140.1, 126.7 (d, 3JC-F = 7.8 Hz), 114.6 (d, 2JC-F = 21.1 Hz), 89.5, 42.8, 32.3, 32.2, 30.3, 28.9, 25.1, 23.2, 22.9, 14.0, 13.8; HRMS (ESI) Calcd for C19H28FO [M + H]+ 291.2124, found 291.2138. Cl

OH Bu Bu

2,3-Dibutyl-1-(4-chlorophenyl)cyclopent-2-enol (4e) Light yellow oil (78 mg, 85%); Rf 0.3 (hexane/EtOAc = 30/1); 1H NMR (400 MHz, CDCl3) δ 7.31-7.25 (m, 4H), 2.50-2.44 (m, 1H), 2.38-2.30 (m, 1H), 2.27-2.06 (m, 4H), 2.02-1.96 (m, 1H), 1.75-1.68 (m, 2H), 1.49-1.32 (m, 4H), 1.26-1.05 (m, 4H), 0.95 (t, J = 7.2 Hz, 3H), 0.78 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 145.6, 142.0, 139.9, 132.0, 128.0, 126.6, 89.5, 42.8, 32.3, 32.2, 30.3, 28.9, 25.1, 23.2, 22.9, 14.0, 13.8; HRMS (ESI) Calcd for C19H28ClO [M + H]+ 307.1829, found 307.1830.

S19

OMe

OH Bu Bu

2,3-Dibutyl-1-(3-methoxyphenyl)cyclopent-2-enol (4f) Light yellow oil (63 mg, 70%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.22 (t, J = 7.9 Hz, 1H), 6.97-6.96 (m, 1H), 6.93-6.91 (m, 1H), 6.77-6.74 (m, 1H), 3.80 (s, 3H), 2.49-2.42 (m, 1H), 2.38-2.25 (m, 2H), 2.22-1.98 (m, 4H), 1.79-1.71 (m, 2H), 1.49-1.33 (m, 4H), 1.29-1.09 (m, 4H), 0.94 (t, J = 7.2 Hz, 3H), 0.78 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.5, 148.9, 141.6, 140.1, 128.9, 117.6, 111.7, 110.9, 89.8, 55.2, 42.7, 32.4, 32.3, 30.3, 28.9, 25.2, 23.2, 22.9, 14.1, 13.8; HRMS (ESI) Calcd for C20H31O2 [M + H]+ 303.2324, found 303.2336. CF3

OH Bu Bu

2,3-Dibutyl-1-(3-trifluoromethylphenyl)cyclopent-2-enol (4g) Light yellow oil (95 mg, 93%); Rf 0.3 (hexane/EtOAc = 30/1); 1H NMR (400 MHz, CDCl3) δ 7.67 (s, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.47 (d, J = 7.7 Hz, 1H), 7.41 (t, J = 7.7 Hz, 1H), 2.542.46 (m, 1H), 2.42-2.35 (m, 1H), 2.30-2.10 (m, 4H), 2.04-1.97 (m, 1H), 1.75-1.67 (m, 2H), 1.51-1.32 (m, 4H), 1.26-1.00 (m, 4H), 0.95 (t, J = 7.2 Hz, 3H), 0.76 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.1, 142.4, 139.8, 130.3 (q, 2JC-F = 31.9 Hz), 128.6, 128.4, 124.4 (q, 1JC-F = 272.0 Hz), 123.2 (q, 3JC-F = 3.7 Hz), 122.1 (q, 3JC-F = 3.8 Hz), 89.5, 42.8, 32.3, 32.2, 30.2, 28.8, 25.0, 23.1, 22.8, 14.0, 13.7; HRMS (ESI) Calcd for C20H28F3O [M + H]+ 341.2092, found 341.2085. Bn OH Bu Bu

1-Benzyl-2,3-dibutylcyclopent-2-enol (4h)

S20

Light yellow oil (58 mg, 68%); Rf 0.3 (hexane/EtOAc = 30/1); 1H NMR (400 MHz, CDCl3) δ 7.26-7.21 (m, 5H), 2.95 (d, J = 13.2 Hz, 1H), 2.74 (d, J = 13.2 Hz, 1H), 2.19-2.02 (m, 6H), 1.80-1.72 (m, 1H), 1.56-1.50 (m, 2H), 1.43-1.35 (m, 4H), 1.30-1.24 (m, 4H), 0.94 (t, J = 7.1 Hz, 3H), 0.89 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 140.7, 139.2, 137.9, 130.3, 127.9, 126.2, 87.8, 44.8, 37.3, 33.3, 31.5, 30.0, 28.8, 24.9, 23.5, 22.8, 14.0 (overlap); HRMS (ESI) Calcd for C20H31O [M + H]+ 287.2375, found 287.2363. Ph OH Ph Ph

1-Phenethyl-2,3-diphenylcyclopent-2-enol (4i) Light yellow oil (90 mg, 88 %); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 7.30-7.20 (m, 7H), 7.15-7.07 (m, 8H), 2.92-2.88 (2H), 2.77-2.26 (m, 2H), 2.50-2.43 (m, 1H), 2.20-2.13 (m, 1H), 1.97-1.89 (m, 1H), 1.85-1.79 (m, 2H);

13

C NMR (100 MHz, CDCl3) δ

142.4, 142.27, 140.1, 136.8, 136.5, 129.7, 128.5, 128.4, 128.3, 128.2, 127.9, 127.2 (overlap), 125.8, 88.3, 41.2, 36.4, 33.1, 30.7; HRMS (ESI) Calcd for C25H25O [M + H]+ 341.1905, found 341.1897.

S21

Table S3. Screening of Reaction Conditions for [3 + 2] Annulation of 1a and 1-Phenyl-1butyne OH

Ph

+ Ph

Et 1a

a

2b

CoX2 (10 mol %) ligand (10 mol %) Zn (50 mol %) DABCO (x mol %) MeCN, 80 °C, 12 h

Ph OH Ph

O

+ Ph

Et 4j

entry

CoX2

ligand

x (mol %)

conc (M)

1

CoBr2

dppm

150

2

CoBr2

dppe

3

CoBr2

4 5

Ph Et

3p yield (%)b 4j

3p

0.3

48

19

150

0.3

67

17

dppp

150

0.3

74

23

CoBr2

dppb

150

0.3

69

28

CoBr2

dpphex

150

0.3

60

18

6

CoBr2

dppf

150

0.3

65

26

7

CoCl2

dppp

150

0.3

47

53

8

CoI2

dppp

150

0.3

83

13

9

Co(acac)2

dppp

150

0.3

15

53

10

CoI2

dppp

150

0.1

91

9

11

CoI2

dppe

150

0.1

78

19

12

CoI2

dppb

150

0.1

63

13

13

CoI2

dppp

50

0.1

88

11

The reaction was performed on using 0.15 mmol of 1a and 0.1 mmol of 2b. bDetermined by

GC using mesitylene as an internal standard. Ph OH Ph Et

3-Ethyl-1,2-diphenylcyclopent-2-enol (4j) Light yellow oil (67 mg, 85%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.40-7.38 (m, 2H), 7.30-7.26 (m, 2H), 7.20-7.14 (m, 4H), 7.00-6.97 (m, 2H), 2.65-2.50 (m, 2H), 2.34-2.23 (m, 4H), 2.12 (s, 1H), 1.10 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 146.9, 145.4, 140.6, 135.6, 129.2, 128.2, 128.0, 126.8, 126.5, 125.0, 89.5, 42.9, 32.2, 22.9, 13.0; HRMS (ESI) Calcd for C19H21O [M + H]+ 265.1592, found 265.1576.

S22

Ph OH Ph Me

3-Methyl-1,2-diphenylcyclopent-2-enol (4k) Light yellow oil (57 mg, 76%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.40-7.38 (m, 2H), 7.30-7.27 (m, 2H), 7.21-7.12 (m, 4H), 7.04-7.02 (m, 2H), 2.61-2.51 (m, 2H), 2.35-2.32 (m, 2H), 2.10 (s, 1H), 1.89 (s, 3H);

13

C NMR (100 MHz, CDCl3) δ 146.9,

141.0, 140.0, 135.5, 129.2, 128.1, 128.0, 126.7, 126.5, 125.0, 89.5, 43.2, 35.4, 15.9; HRMS (ESI) Calcd for C18H19O [M + H]+ 251.1436, found 251.1457. Ph OH Ph Bu

3-Butyl-1,2-diphenylcyclopent-2-enol (4l) Light yellow oil (70 mg, 80%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.41-7.38 (m, 2H), 7.31-7.27 (m, 2H), 7.21-7.16 (m, 4H), 6.99-6.96 (m, 2H), 2.61-2.55 (m, 2H), 2.36-2.33 (m, 2H), 2.28-2.19 (m, 2H), 2.06 (s, 1H), 1.52-1.46 (m, 2H), 1.36-1.27 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H);

13

C NMR (100 MHz, CDCl3) δ 146.9, 144.2, 141.2, 135.7,

129.3, 128.1, 127.9, 127.6, 126.5, 125.0, 89.5, 42.9, 32.6, 30.4, 29.5, 22.8, 14.0; HRMS (ESI) Calcd for C21H25O [M + H]+ 293.1905, found 293.1901. Ph OH

CO2Et

Bu

Ethyl 4-(2-butyl-5-hydroxy-5-phenylcyclopent-1-en-1-yl)benzoate (4m) Light yellow oil (96 mg, 88%); Rf 0.3 (hexane/EtOAc = 10/1); 1H NMR (400 MHz, CDCl3) δ 7.86-7.84 (m, 2H), 7.37-7.35 (m, 2H), 7.29-7.25 (m, 2H), 7.20-7.16 (m, 1H), 7.10-7.08 (m, 2H), 4.31 (q, J = 7.1 Hz, 2H), 2.65-2.58 (m, 2H), 2.43-2.19 (m, 4H), 2.10 (s, 1H), 1.52-1.46 (m, 2H), 1.36-1.28 (m, 5H), 0.87 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.6, 146.3, 145.8, 140.8, 140.7, 129.2, 129.1, 128.7, 128.2, 126.6, 125.0, 89.6, 60.8, 43.1, 32.9, 30.3, 29.6, 22.8, 14.3, 13.9; HRMS (ESI) Calcd for C24H29O3 [M + H]+ 365.2117, found 365.2120.

S23

Ph OH

Cl

Bu

3-Butyl-2-(4-chlorophenyl)-1-phenylcyclopent-2-enol (4n) Light yellow oil (84 mg, 86%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.36-7.34 (m, 2H), 7.30-7.28 (m, 2H), 7.20-7.13 (m, 3H), 6.93-6.91 (m, 2H), 2.65-2.51 (m, 2H), 2.41-2.16 (m, 4H), 2.02 (s, 1H), 1.52-1.45 (m, 2H), 1.35-1.28 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H);

13

C NMR (100 MHz, CDCl3) δ 146.4, 145.0, 140.3, 134.2, 132.6, 130.6, 128.2,

128.1, 126.6, 124.9, 89.5, 43.0, 32.7, 30.3, 29.5, 22.8, 13.9; HRMS (ESI) Calcd for C21H24ClO [M + H]+ 327.1516, found 327.1502. Ph OH OMe Bu

3-Butyl-2-(3-methoxyphenyl)-1-phenylcyclopent-2-enol (4o) Light yellow solid (87 mg, 90%); Rf 0.3 (hexane/EtOAc = 10/1); m.p. 68-69 °C; 1H NMR (400 MHz, CDCl3) δ 7.40-7.38 (m, 2H), 7.30-7.24 (m, 2H), 7.20-7.16 (m, 1H), 7.08 (t, J = 7.9 Hz, 1H), 6.70-6.67 (m, 1H), 6.56 (d, J = 7.6 Hz, 1H), 6.48-6.47 (m, 1H), 3.60 (s, 3H), 2.602.54 (m, 2H), 2.35-2.15 (m, 4H), 2.09 (s, 1H), 1.51-1.45 (m, 2H), 1.34-1.28 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.1, 147.0, 144.2, 141.1, 137.0, 128.9, 128.1, 126.5, 125.0, 121.8, 114.5, 112.7, 89.5, 54.9, 42.7, 32.7, 30.4, 29.6, 22.8, 14.0; HRMS (ESI) Calcd for C22H27O2 [M + H]+ 323.2011, found 323.1995. Ph OH CF3 Bu

3-Butyl-1-phenyl-2-(3-(trifluoromethyl)phenyl)cyclopent-2-enol (4p) Light yellow oil (80 mg, 74%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.40-7.34 (m, 3H), 7.30-7.24 (m, 4H), 7.21-7.13 (m, 2H), 2.70-2.54 (m, 2H), 2.47-2.41 (m, 1H), 2.36-2.29 (m, 1H), 2.24-2.16 (m, 2H), 2.02 (s, 1H), 1.54-1.47 (m, 2H), 1.36-1.27 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H);

13

C NMR (100 MHz, CDCl3) δ 146.2, 145.7, 140.3, 136.6,

132.4, 130.1 (q, 2JC-F = 32.6 Hz), 128.3, 128.2, 126.7, 126.2 (q, 3JC-F = 3.9 Hz), 124.9, 123.4 (q, 4JC-F = 4.0 Hz), 124.1 (q, 1JC-F = 272.4 Hz), 89.5, 43.0, 32.8, 30.3, 29.4, 22.7, 13.9; HRMS S24

(ESI) Calcd for C22H24F3O [M + H]+ 361.1779, found 361.1788. Ph OH

OMe

Et

3-Ethyl-2-(2-methoxyphenyl)-1-phenylcyclopent-2-enol (4q) Light yellow solid (37 mg, 42%); Rf 0.3 (hexane/EtOAc = 10/1); m.p. 64-65 °C; 1H NMR (400 MHz, CDCl3) δ 7.36-7.33 (m, 2H), 7.17 (t, J = 7.6 Hz, 2H), 7.12-7.04 (m, 2H), 6.836.74 (m, 3H), 4.30 (s, 1H), 3.72 (s, 3H), 2.85-2.77 (m, 1H), 2.57-2.50 (m, 1H), 2.40-2.25 (m, 2H), 2.13-2.08 (m, 2H), 1.05 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 156.3, 148.4, 147.1, 138.7, 132.7, 128.1, 127.4, 125.9, 125.6, 125.5, 120.9, 110.8, 89.0, 55.6, 43.3, 32.9, 23.1, 12.8; HRMS (ESI) Calcd for C20H23O2 [M + H]+ 295.1698, found 295.1694. Ph OH

Bu

F

3-Butyl-2-(2-fluorophenyl)-1-phenylcyclopent-2-enol (4r) Light yellow oil (74 mg, 80%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.38-7.36 (m, 2H), 7.26-7.22 (m, 2H), 7.16-7.10 (m, 2H), 6.98-6.81 (m, 3H), 2.75-2.68 (m, 1H), 2.62-2.54 (m, 1H), 2.50-2.43 (m, 1H), 2.39-2.31 (m, 2H), 2.08 (t, J = 7.7 Hz, 2H), 1.491.41 (m, 2H), 1.31-1.22 (m, 2H), 0.84 (t, J = 7.3 Hz, 3H);

13

C NMR (100 MHz, CDCl3) δ

160.2 (d, 1JC-F = 243.0 Hz), 147.5, 146.3, 135.4, 131.5 (d, 4JC-F = 3.9 Hz), 128.7 (d, 3JC-F = 8.4 Hz), 127.9, 126.4, 125.1, 123.6, 123.5, 115.2 (d, 1JC-F = 23.7 Hz), 89.5, 43.2, 32.9, 29.8, 29.7, 22.6, 13.9; HRMS (ESI) Calcd for C21H24FO [M + H]+ 311.1811, found 311.1801. Ph OH Ph

CO2Et

Ethyl 3-(3-hydroxy-2,3-diphenylcyclopent-1-en-1-yl)propanoate (4s) Light yellow oil (83 mg, 82%); Rf 0.3 (hexane/EtOAc = 10/1); 1H NMR (400 MHz, CDCl3) δ 7.39-7.37 (m, 2H), 7.30-7.25 (m, 2H), 7.21-7.17 (m, 4H), 6.99-6.96 (m, 2H), 4.10 (q, J = 7.1 Hz, 2H), 2.63-2.45 (m, 6H), 2.37-2.32 (m, 2H), 2.13 (s, 1H), 1.22 (t, J = 7.1 Hz, 3H);

S25

13

C

NMR (100 MHz, CDCl3) δ 173.0, 146.4, 142.8, 141.5, 135.1, 129.2, 128.2, 128.1, 127.1, 126.6, 124.9, 89.3, 60.5, 42.7, 32.9, 32.4, 25.2, 14.2; HRMS (ESI) Calcd for C22H25O3 [M + H]+ 337.1804, found 337.1784. Ph OH Ph

3-Cyclopropyl-1,2-diphenylcyclopent-2-enol (4t) Light yellow oil (47 mg, 57%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 7.6 Hz, 2H), 7.29 (t, J = 7.6 Hz, 2H), 7.21-7.14 (m, 6H), 2.30-2.18 (m, 4H), 2.12 (s, 1H), 1.86-1.79 (m, 1H), 0.75-0.72 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 146.7, 144.6, 140.7, 135.7, 129.3, 128.2, 128.0, 126.6, 126.5, 125.1, 89.6, 42.6, 28.5, 11.7, 5.9, 5.4; HRMS (ESI) Calcd for C20H21O [M + H]+ 277.1592, found 277.1585. Ph OH S

Bu

3-Butyl-1-phenyl-2-(thiophen-2-yl)cyclopent-2-enol (4u) Light yellow oil (86 mg, 96%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.43-7.41 (m, 2H), 7.33-7.29 (m, 2H), 7.25-7.22 (m, 1H), 7.12 (dd, J = 5.1, 1.1 Hz, 1H), 6.87 (dd, J = 5.1, 3.6 Hz, 1H), 6.71 (dd, J = 3.6, 0.9 Hz, 1H), 2.64-2.39 (m, 4H), 2.31 (t, J = 6.9 Hz, 2H), 2.25 (s, 1H), 1.60-1.52 (m, 2H), 1.45-1.38 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H);

13

C

NMR (100 MHz, CDCl3) δ 146.6, 146.2, 136.5, 134.1, 128.2, 126.8, 126.6, 126.5, 125.0, 124.8, 89.5, 42.5, 33.2, 30.3, 30.0, 23.0, 14.0; HRMS (ESI) Calcd for C19H23OS [M + H]+ 299.1470, found 299.1468.

Ph OH

Ph

n-C6H13

(E)-3-Hexyl-1-phenyl-2-styrylcyclopent-2-enol (4v) Light yellow oil (103 mg, 99%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.44-7.42 (m, 2H), 7.33-7.29 (m, 2H), 7.24-7.19 (m, 5H), 7.14-7.13 (m, 1H), 6.82 (d, J =

S26

16.6 Hz, 1H), 6.31 (d, J = 16.6 Hz, 1H), 2.61-2.31 (m, 4H), 2.25-2.22 (m, 3H), 1.59-1.53 (m, 2H), 1.42-1.34 (m, 6H), 0.93-0.89 (m, 3H);

13

C NMR (100 MHz, CDCl3) δ 148.5, 147.1,

137.9, 137.5, 129.8, 128.4, 128.2, 127.1, 126.5, 126.1, 124.8, 120.1, 88.5, 43.7, 33.3, 31.8, 29.4, 29.3, 28.3, 22.7, 14.1; HRMS (ESI) Calcd for C25H31O [M + H]+ 347.2375, found 347.2368. Ph OH Ph Ph

1,2,3-Triphenylcyclopent-2-enol (4w) Light yellow oil (90 mg, 96%); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.49-7.47 (m, 2H), 7.34-7.30 (m, 2H), 7.25-7.19 (m, 6H), 7.14-7.09 (m, 3H), 6.95-6.93 (m, 2H), 3.09-3.02 (m, 1H), 2.96-2.88 (m, 1H), 2.49 (t, J = 6.8 Hz, 2H), 2.21 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 146.5, 142.5, 140.8, 136.9, 135.6, 129.6, 128.4, 128.3, 128.2, 128.1, 127.4, 127.2, 126.8, 125.0, 89.8, 42.3, 33.8; HRMS (ESI) Calcd for C23H21O [M + H]+ 313.1592, found 313.1571.

S27

Preliminary Study on Enantioselective [3 + 2] Annulation Table S4. Preliminary Screening of Chiral Ligands for the Reaction between 1a and 2aa OH

CoBr2 (10 mol %) ligand (10 mol %) Zn (50 mol %)

Bu

+ Ph

Bu 1a

Bu

Ph

conv (%)

3a (%)b

4a (%)b

%ee of 4ac

1

(R)-Prophos

100

4

96

52

2

(R,R)-Chiraphos

100

1

89

12

3

(R,R)-BDPP

73

7

29

63

4

(S,S)-Me-DuPhos

66

2

51

60

5

(R,R)-Me-BPE

57

3

26

59

6

(R)-BINAP

56

23

23

48

7

(R)-MeO-BIPHEP

60

23

32

66

8

(R)-Segphos

52

10

32

79

9

(R,R,S,S)-DuanPhos

39

0

18

75

10

(R,R)-QuinoxP*

51

0

28 (20)d

93

Ph2P

PPh2

(R)-Prophos

Ph2P

Ph2P

PPh2

(R,R)-Chiraphos

PPh2

(R,R)-BDPP

P

(S,S)-Me-DuPhos

MeO MeO

PPh2 PPh2

O

PPh2 PPh2

O

P H

H P

t-Bu

t-Bu

O (R)-BINAP

(R)-MeO-BIPHEP

(R)-Segphos

P

P

P

O PPh2 PPh2

Bu

Bu 4a

3a

ligand

entry

a

*

+

Bu

DABCO (150 mol %) MeCN, 80 °C, 12 h

2a

Ph OH

O

(R,R,S,S)-DuanPhos

(R,R)-Me-BPE t-Bu Me N P N

P Me

t-Bu

(R,R)-QuinoxP*

The reaction was performed on using 0.15 mmol of 1a and 0.1 mmol of 2a. bDetermined by

GC using mesitylene as an internal standard. cDetermined by chiral HPLC. dIsolated yield is shown in the parentheses. Optical rotation and HPLC analysis of enantioenriched 4a (Table S4, entry 10) [α]21D = +58.6 ° (c = 0.55 in CHCl3, 93% ee sample). HPLC analysis: Daicel CHIRALPAK OJ-H; hexane:i-PrOH = 99:1; detection wavelength = 190 nm; flow rate = 0.5 mL/min. tR = 10.5 min (major) and 11.6 min (minor), 93% ee.

S28

(a)

(b)

!

Figure S2. Determination of ee for 4a obtained for the reaction in Table S4, entry 10. (a) HPLC chromatogram of a racemic sample. (b) HPLC chromatogram of an enantioenriched sample.

S29

Product Transformations Conversion of β-alkenylated ketones into 3,4-dihydro-2H-pyrroles (Scheme 6a) The β-alkenylated ketones (1 mmol each) were converted into the corresponding oxime pivalate esters according to the reported procedure.20 The characterization data are described below. PivO N Bu Bu

Me

(4E)-4-Butyl-1-(p-tolyl)non-4-en-1-one O-pivaloyl oxime (5a) Light yellow oil (270 mg, 70 %); Rf 0.4 (hexane/EtOAc = 10/1); 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 5.16 (t, J = 7.1 Hz, 1H), 2.91-2.87 (m, 2H), 2.38 (s, 3H), 2.24-2.20 (m, 2H), 2.06-1.98 (m, 4H), 1.34-1.27 (m, 17H), 0.90 (t, J = 6.7 Hz, 6H);

13

C NMR (100 MHz, CDCl3) δ 175.2, 166.7, 140.7, 137.8, 131.2, 129.3, 127.2,

126.2, 38.8, 33.7, 23.2, 30.8, 29.8, 27.8, 27.4, 27.3, 26.5, 22.8, 22.4, 21.4, 14.0; HRMS (ESI) Calcd for C25H40NO2 [M + H]+ 386.3059, found 386.3045. PivO N Bu Bu

MeO

(4E)-4-Butyl-1-(4-methoxyphenyl)non-4-en-1-one O-pivaloyl oxime (5b) Light yellow oil (260 mg, 65 %); Rf 0.3 (hexane/EtOAc = 10/1); 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.7 Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 5.16 (t, J = 7.1 Hz, 1H), 3.84 (s, 3H), 2.90-2.86 (m, 2H), 2.24-2.20 (m, 2H), 2.06-1.98 (m, 4H), 1.34-1.23 (m, 1716H), 0.90 (t, J = 6.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 175.2, 166.2, 161.5, 137.8, 128.8, 126.4, 126.2, 113.9, 55.3, 38.8, 33.8, 32.2, 30.8, 29.8, 27.7, 27.4, 27.3, 27.0, 22.8, 22.4, 14.0; HRMS (ESI) Calcd for C25H40NO3 [M + H]+ 402.3008, found 402.3000. PivO N Bu Bu

2-(2-Butylhept-2-en-1-yl)-3,4-dihydronaphthalen-1(2H)-one O-pivaloyl oxime (5c) S30

Light yellow oil (330 mg, 83 %); Rf 0.4 (hexane/EtOAc = 10/1); 1H NMR (400 MHz, CDCl3) δ 8.19 (dd, J = 7.9, 1.0 Hz, 1H), 7.33 (td, J = 7.4, 1.3 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 7.7 Hz, 1H), 5.20 (t, J = 7.1 Hz, 1H), 3,68-3.62 (m, 1H), 3.01-2.92 (m, 1H), 2.70-2.64 (m, 1H), 2.37-2.32 (m, 1H), 2.20-2.13 (m, 1H), 2.09-1.81 (m, 6H), 1.35-1.26 (m, 1719H), 0.93-0.89 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 175.3, 174.0, 164.9, 139.6, 135.8, 130.6, 128.9, 128.6, 126.4, 126.3, 38.9, 35.9, 32.2, 31.6, 31.1, 29.5, 27.5, 27.4, 26.5, 24.2, 23.9, 22.9, 22.4, 14.0; HRMS (ESI) Calcd for C26H40NO2 [M + H]+ 398.3059, found 398.3060. Copper-Catalyzed aza-Heck Cyclization: The procedure was adapted from the literature.20 In an argon-filled glove box, a 4-mL vial equipped with a magnetic stirrer bar was charged sequentially with Cu(II)(2-ethylhexanoate)2 (7.0 mg, 0.020 mmol), oxime ester substrate (0.20 mmol) and anhydrous benzonitrile (2.6 mL). The vial was closed and removed from the glove box, and the mixture was placed in a preheated oil bath (100 °C) until complete consumption of starting material was observed (TLC analysis). The mixture was then cooled to room temperature and concentrated in vacuo (40 °C, ca. 1.0 mmHg). The residue was purified by flash chromatography on silica gel to afford the desired product.

Me

N

Bu Pr

(E)-2-Butyl-2-(pent-1-en-1-yl)-5-(p-tolyl)-3,4-dihydro-2H-pyrrole (6a) Light yellow oil (50 mg, 88 %); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 5.65 (d, J = 15.6 Hz, 1H), 5.47-5.39 (m, 1H), 2.93-2.87 (m, 2H), 2.38 (s, 3H), 2.01-1.91 (m, 2H), 1.89-1.87 (m, 1H), 1.73-1.66 (m, 2H), 1.39-1.20 (m, 7H), 0.92-0.85 (m, 6H);

13

C NMR (100 MHz, CDCl3) δ 170.4, 140.3,

135.7, 132.3, 129.0, 127.7, 127.4, 79.4, 41.2, 34.9, 34.7, 33.0, 26.7, 23.3, 22.6, 21.4, 14.1, 13.7; HRMS (ESI) Calcd for C20H30N [M + H]+ 284.2378, found 284.2390.

MeO

N

Bu Pr

(E)-2-Butyl-5-(4-methoxyphenyl)-2-(pent-1-en-1-yl)-3,4-dihydro-2H-pyrrole (6b) Light yellow oil (51 mg, 85 %); Rf 0.3 (hexane/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3) δ 7.83-7.79 (m, 2H), 6.92-6.89 (m, 2H), 5.65 (dt, J = 15.6, 1.2 Hz, 1H), 5.47-5.39 (m, 1H),

S31

3.83 (s, 3H), 2.96-2.82 (m, 2H), 2.01-1.94 (m, 3H), 1.90-1.83 (m, 1H), 1.75-1.68 (m, 2H), 1.42-1.24 (m, 6H), 0.91-0.85 (m, 6H);

13

C NMR (100 MHz, CDCl3) δ 169.9, 161.2, 135.8,

129.3, 127.8, 127.3, 113.6, 79.3, 55.3, 41.2, 34.8, 34.7, 33.0, 26.7, 23.3, 22.6, 14.1, 13.7; HRMS (ESI) Calcd for C20H30NO [M + H]+ 300.2327, found 300.2323.

N

Bu Pr

(E)-2-Butyl-2-(pent-1-en-1-yl)-3,3a,4,5-tetrahydro-2H-benzo[g]indole (6c) Light yellow oil (52 mg, 88 %); Rf 0.3 (hexane/EtOAc = 25/1); 1H NMR (400 MHz, CDCl3) Major diastereomer: δ 8.18 (dd, J = 7.7, 1.1 Hz, 1H), 7.32 (td, J = 7.4, 1.4 Hz, 1H), 7.24-7.18 (m, 2H), 5.53-5.49 (m, 1H), 5.39-5.32 (m, 1H); 3.03-2.84 (m, 3H), 2.24-2.19 (m, 2H), 1.991.94 (m, 2H), 1.86-1.56 (m, 4H), 1.49-1.26 (m, 6H), 0.92-0.84 (m, 6H); Minor diastereomer: 8.15 (dd, J = 7.7, 1.1 Hz, 1H), 7.32 (m, 1H), 7.24-7.18 (m, 2H), 5.88 (dt, J = 15.7, 1.3 Hz, 1H), 5.59-5.55 (m, 1H); 3.03-2.84 (m, 3H), 2.24-2.19 (m, 2H), 2.06-2.01 (m, 2H), 1.86-1.56 (m, 4H), 1.49-1.26 (m, 6H), 0.92-0.84 (m, 6H);

13

C NMR (100 MHz, CDCl3; both

diastereomers): δ 171.6, 170.8, 141.0, 140.8, 137.6, 133.8, 130.5, 130.4, 130.3, 128.8, 128.7, 128.0, 127.5, 126.3, 126.3, 126.2, 126.1, 78.1, 77.5, 46.9, 46.1, 41.8, 40.7, 40.6, 39.7, 34.8, 34.7, 30.2, 30.0, 30.0, 29.6, 27.0, 26.8, 23.3, 22.6, 22.6, 14.2, 14.1, 13.8, 13.7; HRMS (ESI) Calcd for C21H30N [M + H]+ 296.2378, found 296.2369. Conversion of cyclopentenol to CpX–RhIII complex (Scheme 6b) Ph Ph Ph

Cyclopenta-1,3-diene-1,2,3-triyltribenzene (7) To 1,2,3-triphenylcyclopent-2-enol (4w, 70 mg, 0.22 mmol) dissolved in ethanol (2 mL) was added a few drops of concentrated HCl. The reaction mixture was then stirred at room temperature for 10 min. The resulting white precipitates were collected by filtration and washed with chilled diethyl ether (3 mL). The crude product was then dried under vacuum to obtain the title compound (50 mg, 76%), whose NMR spectra showed good agreement with the literature data.21

S32

Ph Ph Cl

Ph Rh Cl 2

1,2,3-Triphenylcyclopentadienylrhodium(III) chloride dimer (8) The rhodium complex was synthesized according to the literature procedure.22 To a solution of the cyclopenta-1,3-diene-1,2,3-triyltribenzene (50 mg, 0.17 mmol, 1.2 equiv) and RhCl3 •3H2O (37 mg, 0.14 mmol, 1 equiv) in EtOH (2 mL) were added a few drops of water. The resultant orange-brown mixture was stirred at 85 °C for 2 days. The orange-red precipitate was isolated by vacuum filtration and rinsed successively with cold ethanol and pentane. The solid was then redissolved in CH2Cl2, and the resultant solution was filtered through a short plug of Celite. The volatiles were evaporated under reduced pressure to obtain the desired complex as orange solid (65 mg, 82 %). Recrystallization from CH2Cl2 afforded single crystals suitable for X-ray diffraction analysis (Figure S1).23 1

H NMR (400 MHz, DMSO-d6) δ 7.60-7.58 (m, 2H), 7.45-7.33 (m, 9H), 7.28-7.24 (m, 4H),

6.43 (s, 2H);

13

C NMR (100 MHz, DMSO-d6) δ 131.7, 131.1, 130.4, 130.0, 129.6, 128.8,

128.7, 128.4, 110.92 (d, J = 6.3 Hz), 99.02 (d, J = 5.5 Hz), 81.97 (d, J = 8.2 Hz); HRMS (ESI) Calcd for C48H43Cl4Rh2 [M + H]+ 965.0229, found 965.0276.

Figure S3. ORTEP drawing of 8 (thermal ellipsoids set at 50% probability).

S33

Control Experiments Ring-Opening of Cyclopropanol to Ketone To probe the role of each component of the catalytic system on the ring-opening of cyclopropanol, conversion of 1-benzylcyclopropanol (1j) into 1-phenylbutan-2-one was examined under various conditions in the absence of alkyne (Table S5). Key observations and their implications are summarized as follows. Note that similar reactivity trends were made for the ring-opening of 1-phenylcyclopropanol (1a). 1) The ring-opening was fast when both CoBr2 and Zn are present (entries 1, 2, 4 and 5) and became sluggish in the absence of Zn (e.g., entries 3 and 6). This suggests that a cobalt(I) species generated from Co(II) and Zn is responsible for the smooth ring-opening. 2) Curiously, Zn dust (alone or with DABCO) promoted the reaction to full conversion at 12 h (entries 8 and 10). Although the mechanism of this process is unknown (we suspect Zn2+ on the surface of Zn dust plays a role), this Zn-mediated process seems kinetically less important as judged from the low conversions at 1 h. 3) ZnBr2 (alone or with DABCO) promoted the reaction only sluggishly (entries 12 and 13). Thus, ZnBr2 generated from CoBr2 and Zn under the standard conditions is unlikely to play a major role in the ring-opening process (i.e., formation of zinc homoenolate is less likely). 4) While CoBr2 alone or DABCO alone was almost ineffective (entries 9 and 11), their combination promoted the ring-opening to some extent (entry 7; see also entry 3). While this demonstrates the feasibility of Co(II)-mediated ring-opening, its relevance to the reaction under the standard conditions would be limited. Overall, a cobalt(I) species generated from the cobalt(II) precatalyst and Zn seems to play a major role in the ring-opening of cyclopropanol to form a cobalt homoenolate, and formation of a zinc homoenolate from cyclopropanol and Zn2+ is less likely.

S34

Table S5. Ring-Opening of 1-Benzylcyclopropanol (1j) under Various Conditions CoBr2 (10 mol%) dppe (10 mol%) Zn (50 mol%)

OH Bn 1j

entry

DABCO (150 mol%) DMSO, 80 °C

O Bn

yield (%)a

deviation from standard conditions

at 1 h

a

at 12 h

1

none

46

100

2

DABCO was omitted

67

100

3

Zn was omitted

N.D.

36

4

dppe was omitted

82

100

5

dppe and DABCO were omitted

23

100

6

Zn and DABCO were omitted

8

35

7

dppe and Zn were omitted

N.D.

71

8

CoBr2 and dppe were omitted

3

100

9

CoBr2 alone was used

N.D.

5

10

Zn alone was used

4

100

11

DABCO alone was used

N.D.

3

12

ZnBr2 (10 mol%) and DABCO were used instead of std. cond.

N.D.

20

13

ZnBr2 (10 mol%) was used instead of std. cond.

N.D.

16

Determined by GC using mesitylene as an internal standard.

Deuterium-Labeling Experiments and Effect of Radical Scavengers The fate of the hydroxyl proton of cyclopropanol and the origin of the vinylic proton in the βalkenylation product were probed by deuterium-labeling experiments. The reaction of deuterium-labeled cyclopropanol 1a-d (65% D) with 2a resulted in the adduct with partial deuterium incorporation into the vinylic and the carbonyl α-positions (Scheme S1a). A similar pattern of deuterium incorporation was observed in the reaction of 1a with 2a in the presence of CD3OD (1.5 equiv), and the degree of deuterium incorporation increased with an increased amount (10 equiv) of CD3OD (Scheme S1b). These observations suggest that not only the alcoholic protons but also the carbonyl α-protons are responsible as the proton source for the vinylic position. Radical scavengers such as TEMPO and 1,1-diphenylethylene did not significantly interfere with the reaction (Scheme S1c).

S35

Scheme S1. Labeling and Control Experiments. (a) β-Alkenylation between Deuterated Cyclopropanol 1a-d and Alkyne 2a. (b) β-Alkenylation between Cyclopropanol 1a and Alkyne 2a in the Presence of CD3OD. (c) β-Alkenylation between Cyclopropanol 1a and Alkyne 2a in the Presence of Radical Scavenger.

(a) OD

Bu

+ Ph

Bu

1a-d (68% D)

CoBr2 (10 mol%) dppe (10 mol%) Zn (50 mol%) DABCO (150 mol%) DMSO, 80 °C, 12 h

2a

0.08D O Bu

Ph 0.20D

80%

(b) OH

Bu

+ Ph

Bu 1a

Bu

CoBr2 (10 mol%) dppe (10 mol%) Zn (50 mol%) DABCO (150 mol%) CD3OD (n equiv) DMSO, 80 °C, 12 h

2a

O

0.20D (n = 1.5) 0.54D (n = 10) Bu

Ph

Bu 0.55D (n = 1.5) 1.29D (n = 10) 76% (n = 1.5) 38% (n = 10)

(c) OH

Bu

+ Ph

Bu 1a

2a

CoBr2 (10 mol%) dppe (10 mol%) Zn (50 mol%) DABCO (150 mol%) additive (1 equiv) DMSO, 80 °C, 12 h

O Bu

Ph Bu

72% (TEMPO) 90% (Ph2C=CH2)

Preparation of 1a-d: To a 4-mL vial equipped with a magnetic stirrer bar was charged sequentially with 1a (0.45 mmol), anhydrous CH3CN (1.0 mL) and D2O (0.1 mL). The mixture was stirred at room temperature for 12 h. Upon removal of the solvent under vacuum, the product was obtained as a light yellow oil (quantitative yield). The deuteration rate of the alcohol was determined to be 68% by 1H NMR (Figure S4).

S36

0.000

1.261 1.255 1.243 1.056 1.044 1.038

2.615 2.373 2.162

7.351 7.347 7.336 7.331 7.321 7.313 7.308 7.301 7.295 7.292 7.286 7.251 7.241 7.236 7.231 7.225 7.224 7.220 7.213 7.208 7.203 7.198

JF09-621H BBFO2

OD/H Ph 1a-d (68% D)

5

4

3

2

1

0 ppm

1.91

6

2.00

7

0.32

8 3.81 1.20

9

Figure S4. 1H NMR spectrum (400 MHz, CDCl3) of 1a-d. Reaction of 1a-d with 2a: The reaction was performed on a 0.2 mmol scale according to the general procedure. Silica gel chromatography of the crude product afforded (E)-4-butyl-1phenylnon-4-en-1-one as a light yellow oil (43.6 mg, 80%). The 1H NMR integrations at the vinyl position (5.16 ppm) and the carbonyl α-position (3.05 ppm) were determined to be 0.92 and 1.80, respectively (Figure S5a). In agreement with this observation, 2H NMR spectrum of the product showed peaks at vinyl (5.19 ppm) and α (3.05 ppm) positions in an integration ratio of 1:2.1 (Figure S5b).

S37

Bu

7.5

7.0

6.5

6.0

5.5

5.0

4.5

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

ppm

6.23

8.0

8.36

8.5

80%

1.00 2.05

9.0

0.20D

2a

2.04

9.5

Bu

1.80

1a-d (68% D)

Bu

Ph

DABCO (150 mol %) DMSO, 80 °C, 12 h

Bu

4.19

+ Ph

0.08D O

2.04

OD

CoBr2 (10 mol %) dppe (10 mol %) Zn (50 mol %)

0.92

(a)

5.175 5.157 5.140 3.073 3.060 3.057 3.053 3.049 3.045 3.034 2.429 2.410 2.391 2.072 2.055 2.035 2.022 2.005 1.987 1.690 1.409 1.405 1.391 1.383 1.373 1.361 1.352 1.345 1.338 1.321 1.311 1.302 1.293

7.969 7.952 7.948 7.566 7.564 7.560 7.550 7.545 7.540 7.530 7.527 7.524 7.471 7.451 7.437 7.433 7.257

JF09-623H BBFO1

10

9

8

7

6

5 0.47

11

3.054

(b)

4

3

2

1

ppm

1.00

5.186

JF09-623D BBFO1

Figure S5. (a) 1H NMR (400 MHz, CDCl3) and (b) 2H NMR (61.4 MHz, CDCl3) spectra of the product of the reaction in Scheme S1a. S38

Reaction of 1a with 2a in the presence of CD3OD (1.5 equiv): The reaction was performed on a 0.3 mmol scale according to the general procedure except for the addition of CD3OD (1.5 equiv). Silica gel chromatography of the crude product afforded (E)-4-butyl-1-phenylnon-4en-1-one as a light yellow oil (62.1 mg, 76%). The 1H NMR integrations at the vinyl position and the carbonyl α-position were determined to be 0.80 and 1.45, respectively (Figure S6a). In agreement with this observation, 2H NMR spectrum of the product showed peaks at the vinyl and α positions with an integration ratio of 1:2.8.

7.970 7.952 7.949 7.571 7.568 7.565 7.555 7.550 7.545 7.534 7.531 7.528 7.475 7.456 7.441 7.437 7.258 5.173 5.156 5.138 3.074 3.062 3.058 3.054 3.050 3.046 3.035 2.427 2.410 2.391 2.071 2.053 2.033 2.020 2.003 1.986 1.632 1.408 1.404 1.389 1.381 1.371 1.359 1.351 1.344 1.337 1.320 1.310 1.302 1.292 1.274 1.258 0.947 0.926 0.908 0.888 0.871 0.000

JF09-618H BBFO2

(a) OH

Bu

+ Ph

Bu 1a

CoBr2 (10 mol %) dppe (10 mol %) Zn (50 mol %) DABCO (150 mol %) CD3OD (1.5 equiv) DMSO, 80 °C, 12 h

2a

0.20D

O

Bu

Ph Bu 0.55D 76%

S39

1 6.12

2 8.49

3

4.09

4

2.07

5

1.45

6 0.80

7 1.00 1.98

8 1.96

9

0 ppm

10

9

8

7

6

5

4

0.36

11

3

2

1

ppm

1.00

5.193

(b)

3.047

JF09-618D-redo2 BBFO2

Figure S6. (a) 1H NMR (400 MHz, CDCl3) and (b) 2H NMR (61.4 MHz, CDCl3) spectra of the product of the reaction in Scheme S1b (1.5 equiv CD3OD). Reaction of 1a with 2a in the presence of CD3OD (10 equiv): The reaction was performed on a 0.3 mmol scale according to the general procedure except for the addition of CD3OD (10 equiv). Silica gel chromatography of the crude product afforded (E)-4-butyl-1-phenylnon-4en-1-one as a light yellow oil (31.0 mg, 38%). The 1H NMR integrations at the vinyl position and the carbonyl α-position were determined to be 0.46 and 0.71, respectively (Figure S7a). In agreement with this observation, 2H NMR spectrum of the product showed peaks at the vinyl and α positions with an integration ratio of 1:2.6 (Figure S7b).

S40

3.074 3.055 3.051 3.046 3.035 3.026 3.007 2.410 2.392 2.069 2.052 2.032 2.003 1.988 1.600 1.388 1.380 1.370 1.350 1.344 1.336 1.320 1.309 1.301 1.291 1.273 1.257 0.947

5.172 5.154 5.136

7.970 7.952 7.949 7.574 7.571 7.568 7.557 7.552 7.548 7.537 7.534 7.531 7.477 7.458 7.440 7.258

JF09-619H BBFO2

(a)

OH

Bu

+ Ph

CoBr2 (10 mol %) dppe (10 mol %) Zn (50 mol %)

Bu 1a

DABCO (150 mol %) CD3OD (10 equiv) DMSO, 80 °C, 12 h

2a

0.54D

O

Bu

Ph Bu 1.29D 38%

1

0 ppm

6.18

2 8.12

3

4.10

4

2.08

5

0.71

6 0.46

7 1.00 2.03

8 1.98

9

10

9

8

7

6

5

4

0.38

11

3.041

(b)

3

2

1

ppm

1.00

5.201

JF09-619D BBFO2

Figure S7. (a) 1H NMR (400 MHz, CDCl3) and (b) 2H NMR (61.4 MHz, CDCl3) spectra of the product of the reaction in Scheme S1b (10 equiv CD3OD). S41

Reaction of 1a with 2a in the presence of radical scavenger: The reaction was performed on a 0.1 mmol scale according to the general procedure except for the addition of TEMPO (15.6 mg, 0.10 mmol) or 1,1-diphenylethylene (18.0 mg, 0.10 mmol). The yield was determined to be 72% and 90% for the former and the latter cases, respectively, by GC using mesitylene as an internal standard.

S42

Computational Studies All the density functional theory (DFT) calculations were performed using Gaussian 09.24 Geometry optimizations were performed with the M06L functional

25

using the

Stuttgart/Dresden effective core potential (SDD)26 for cobalt and the 6-31G(d) basis set for all other atoms. This set of basis sets is referred to as 631SDD. The M06L/631SDD calculations provided the energies (E1) of the intermediates and transition states. Harmonic frequency calculations were performed for each stationary point to ensure that it has no imaginary frequency (for ground state) or only one imaginary frequency (for transition state) and to obtain free energy correction values (Gcorr). Single-point energy calculations were performed with the M06L functional and the def2-TZVP basis set27 for all atoms, using the SMD solvation model28 for acetonitrile. The thus-obtained energy (E2) was corrected by Gcorr, and the resulting value was used to discuss relative free energies. As shown in Figure S10, the optimized structures were visualized using CYLview.29 Summary of Reaction Pathways, Energy Diagrams and Representative Structures O

ΔG (kcal/mol) Ph2 P

Ph2 P

P Ph2

CP1s +11.2 Ph2 P

P Ph2

O

Co

O

P Ph2

Co

TS1s +11.9

Me Me

Co Me

Ph2 P

Me

+20.2 TS2s

Ph2 P

P Ph2

O

P Ph2

CP2s +1.2

Me O

Me

Me

TS3s +3.5

CP4s +2.8

Co

Me

Me

Co

CP3s –2.0

O Ph2 P

O Me

Ph2 P

P Ph2

Me

Co Me

P Ph2

Me Me

Co Me

Me

Ph2 P

P Ph2

Co

Me

Me O

CP5s –24.3

Figure S8. Free energy diagram (S = 0) for (dppe)Co(I)-mediated [3 + 2] annulation of 1methylcyclopropanol and 2-butyne (SMD(MeCN)-M06L/def2-TZVP//M06L/631SDD).

S43

Me

ΔG (kcal/mol)

O O

Ph2 P

Me

P Ph2

Ph2 P

O

Ph2 P

P Ph2

Me

Co

Me

Co

+24.3 TS2t

Me

+12.3 CP3t Ph2 P

P Ph2

CP2t –4.0

Ph2 P

Co

Me

+8.4 TS1t

CP1t 0.0

P Ph2

P Ph2

Me

Co

O Ph2 P

Me

P Ph2

O

O

Me

Co Me

Me

–2.8

Me

CP4t

TS3t

–12.7

Co

Ph2 P

P Ph2

P Ph2

Co Me

Me

Me

O

Ph2 P

Me

O

Co Me

Me

CP5t –26.3

Figure S9. Free energy diagram (S = 1) for (dppe)Co(I)-mediated [3 + 2] annulation of 1methylcyclopropanol and 2-butyne (SMD(MeCN)-M06L/def2-TZVP//M06L/631SDD).

1 3

2

1

3

2

a 1

a

2

3

b

b

1

2

3

C1-C3: 1.88 Co-C1: 2.10 Co-C3: 2.07 Co-O: 1.94 TS1s

Co-C3: 1.98 Co-O: 1.97

C3-Ca: 2.08 Co-C3: 2.09 Co-Ca: 1.84 Co-Cb: 1.83

CP2s

TS2s

1 2

1

2

2 3

3

2

b b

3

C1-C3: 1.85 Co-C1: 2.15 Co-C3: 2.24 Co-O: 2.05

a

a

3

TS1t

Co-O: 1.89 Co-C1: 2.17 TS3s

1 1

C1-Ca: 2.11 Co-Cb: 2.04

Co-C3: 2.02 Co-O: 2.20

C3-Ca: 2.18 Co-C3: 2.28 Co-Ca: 1.92 Co-Cb: 1.95

CP2t

TS2t

C1-Ca: 2.11 Co-Cb: 2.02 Co-O: 2.03 Co-C1: 2.25 TS3t

Figure S10. Structures of representative intermediates and transition states (color code: pink, cobalt; orange, phosphorus; red, oxygen; grey, carbon; white, hydrogen). Bond lengths are given in Å. S44

Table S6. Energy Data (hartrees). E1

Gcorr

E2

E2 + Gcorr

CP1s

-1531.204999

0.381688

-1531.536245

-1531.154557

TS1s

-1531.181925

0.379757

-1531.515022

-1531.135265

CP2s

-1531.202257

0.379931

-1531.537797

-1531.157866

CP3s

-1531.198502

0.380654

-1531.534887

-1531.154233

TS2s

-1531.210051

0.381241

-1531.54696

-1531.165719

CP4s

-1531.192433

0.382083

-1531.526091

-1531.144008

TS3s

-1531.262143

0.386526

-1531.59337

-1531.206844

CP5s

-1531.183811

0.37778

-1531.523877

-1531.146097

CP1t

-1531.184859

0.378511

-1531.525369

-1531.146858

TS1t

-1531.178149

0.376865

-1531.515729

-1531.138864

CP2t

-1531.245869

0.385361

-1531.580652

-1531.195291

CP3t

-1531.162216

0.381293

-1531.497334

-1531.116041

TS2t

-1531.193973

0.382096

-1531.528598

-1531.146502

CP4t

-1531.181246

0.38218

-1531.515355

-1531.133175

TS3t

-1531.146016

0.373565

-1531.487721

-1531.114156

CP5t

-1531.140631

0.374566

-1531.483733

-1531.109167

2-butyne

Cartesian Coordinates of Optimized Structures 2-butyne C C C H H H C H H H

-0.000000 0.000000 0.000000 0.509064 0.511005 -1.020069 -0.000000 -0.509064 -0.511005 1.020069

0.000000 0.000000 -0.000000 0.883965 -0.882845 -0.001120 -0.000000 0.883965 -0.882845 -0.001120

0.605543 -0.605543 -2.055828 -2.461390 -2.461390 -2.461390 2.055828 2.461390 2.461390 2.461390

-0.281522 0.287293 -1.079758 -0.590913 -1.617245 -0.199388 0.465478

4.042813 4.707086 4.529223 2.676066 2.337104 2.440006 2.991423

CP1s C H H C H H C

0.762214 1.410538 0.206034 1.323046 1.124701 2.311850 0.036872

S45

C H H H O Co P P C H H C H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

0.351829 0.089833 -0.233220 1.414204 -1.132491 -0.054830 -1.532752 1.369961 0.546900 1.178431 0.427399 -0.816659 -0.709665 -1.462775 -2.074359 -2.320231 -2.147213 -2.626232 -2.236650 -2.441746 -1.962039 -2.678517 -2.812718 -2.483355 -2.902785 -3.106697 -4.061491 -3.355354 -5.239797 -3.885629 -4.540464 -2.612954 -5.479010 -5.976393 -4.731564 -6.403372 2.270285 3.568764 1.550375 4.135086 4.142818 2.119057 0.519172 3.414924 5.146492 1.541051 3.858803 2.712085 3.757394 2.654000 4.722520 3.818275 3.619474 1.830245 4.654877 5.531046 3.561692 5.411142

1.936163 2.277122 2.520727 2.153441 0.001666 -0.422379 -0.424511 -0.378680 -0.346931 -0.831446 0.703734 -1.014675 -2.103189 -0.834031 1.291952 2.133397 1.828734 3.475277 1.718716 3.178764 1.199608 4.004689 4.115969 3.584149 5.059451 -1.337255 -1.385982 -2.001000 -2.104045 -0.849725 -2.712414 -1.939802 -2.769013 -2.141935 -3.223528 -3.328282 1.220094 1.328742 2.398106 2.579676 0.427178 3.644883 2.337812 3.740086 2.645250 4.544885 4.716032 -1.615906 -1.424142 -2.815392 -2.407912 -0.489950 -3.802736 -2.970403 -3.598903 -2.247140 -4.732420 -4.368165

2.818672 1.809748 3.542842 2.984930 2.541543 1.024260 -0.467153 -0.524947 -2.207641 -2.962599 -2.505900 -2.069388 -1.972079 -2.939071 -0.853039 0.243302 -2.143817 0.049389 1.249944 -2.335286 -3.014688 -1.240849 0.910211 -3.345331 -1.391524 -0.283257 -1.306148 0.922306 -1.132896 -2.240297 1.096382 1.718997 0.069325 -1.934085 2.038603 0.205494 -0.444710 0.068781 -0.698780 0.308358 0.283846 -0.467965 -1.053319 0.039051 0.707086 -0.673656 0.227837 -0.766275 -1.680701 -0.050738 -1.867554 -2.241406 -0.237102 0.648640 -1.144540 -2.579203 0.326579 -1.291974

S46

TS1s C H H C H H C C H H H O Co P P C H H C H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C

-0.848393 -1.546015 -0.302027 -1.372078 -1.184382 -2.382791 -0.011849 -0.371893 0.059640 0.019171 -1.457728 1.156039 0.031719 1.535939 -1.378740 -0.554200 -1.188321 -0.430401 0.806036 0.691608 1.449255 2.102957 2.415600 2.151326 2.764641 2.352123 2.489300 1.915047 2.794214 3.004551 2.512493 3.054041 3.101670 4.054592 3.345835 5.225597 3.882720 4.523282 2.606733 5.459689 5.960780 4.710101 6.378421 -2.280122 -3.579884 -1.569677 -4.157545 -4.146796 -2.149775 -0.536274 -3.447707 -5.169948 -1.579951 -3.900723 -2.717135 -3.773404 -2.635639 -4.727441

0.270792 -0.305259 1.015413 0.735853 1.800535 0.407765 -0.499478 -1.946543 -2.314147 -2.558934 -2.094268 -0.034058 0.429964 0.412109 0.359701 0.318646 0.794890 -0.733162 0.994277 2.082241 0.818806 -1.293521 -2.117242 -1.837507 -3.448346 -1.698717 -3.176988 -1.221905 -3.985035 -4.075017 -3.587987 -5.031450 1.343585 1.391137 2.024025 2.123221 0.842145 2.750455 1.964400 2.804757 2.159285 3.274514 3.375007 -1.238132 -1.343215 -2.418659 -2.592131 -0.440051 -3.663518 -2.362876 -3.754959 -2.654139 -4.565937 -4.729651 1.597486 1.385567 2.823274 2.374270

3.897497 4.507911 4.476482 2.555985 2.359566 2.306055 2.945536 2.702138 1.764688 3.529803 2.662016 2.576909 1.060161 -0.443347 -0.490334 -2.173743 -2.931792 -2.465681 -2.042150 -1.944849 -2.915131 -0.831257 0.261552 -2.120220 0.065900 1.267808 -2.312789 -2.988272 -1.221921 0.923694 -3.321126 -1.373339 -0.274278 -1.299028 0.922956 -1.135827 -2.226487 1.087179 1.722763 0.058186 -1.938387 2.023111 0.186498 -0.411190 0.100426 -0.678852 0.321602 0.326842 -0.466581 -1.028445 0.035636 0.718310 -0.683603 0.208446 -0.752304 -1.649521 -0.085240 -1.865135

S47

H C H C H H H

-3.850878 -3.589801 -1.804651 -4.637315 -5.544650 -3.513997 -5.385131

0.432193 3.815657 2.993613 3.591009 2.197108 4.765436 4.364022

-2.174585 -0.300827 0.601130 -1.189139 -2.562836 0.226021 -1.358550

1.117717 2.097668 0.378849 1.070036 0.845009 1.031433 2.108394 0.854847 0.219125 0.593530 -0.834487 0.061003 -0.104521 -0.164375 -0.036591 1.031569 -0.478955 -0.684205 -1.779444 -0.421635 0.457984 -1.649299 -1.823916 -2.703137 -3.009916 -1.013626 -3.893866 -2.597623 -4.051406 -3.122745 -4.699562 -4.981137 1.181053 1.007953 2.398796 2.034080 0.057958 3.426000 2.515941 3.244398 1.888605 4.368886 4.045391 -1.412592 -1.080240 -2.764595 -2.073266 -0.035786 -3.755763

4.688988 5.131543 5.480628 4.405552 3.519070 3.587928 3.413168 4.617233 2.476196 2.290184 2.797310 1.018086 -0.457290 -0.531623 -2.165040 -2.404926 -2.925707 -2.122139 -2.099979 -2.997349 2.436647 -0.476479 0.498504 -1.362356 0.577554 1.196960 -1.280839 -2.132104 -0.311462 1.336460 -1.982946 -0.248980 -0.568585 -1.338268 0.089592 -1.449245 -1.845873 -0.021326 0.695162 -0.791103 -2.049525 0.498300 -0.876186 -0.372061 -0.181134 -0.307112 0.038719 -0.207111 -0.097346

CP2s C H H H C C H H C H H Co P P C H H C H H O C C C C H C H C H H H C C C C H C H C H H H C C C C H C

-1.661397 -1.440306 -1.475231 -2.715519 -0.777964 0.695377 0.872083 1.060246 1.358476 2.374727 1.458108 0.033993 1.495544 -1.452642 0.750076 0.655707 1.408600 -0.627032 -0.548332 -1.236191 -1.268569 2.490697 3.484539 2.235726 4.204406 3.696025 2.954542 1.471250 3.940763 4.977270 2.744486 4.503600 2.804692 3.960813 2.603715 4.894735 4.134094 3.537170 1.701418 4.683821 5.791732 3.372607 5.416634 -2.791842 -4.137910 -2.421783 -5.090305 -4.446002 -3.373293

S48

H C H H H C C C C H C H C H H H

-1.369293 -4.713890 -6.133805 -3.066916 -5.459840 -2.353025 -3.222545 -2.117500 -3.839451 -3.429468 -2.736561 -1.429850 -3.595907 -4.512887 -2.545391 -4.077199

-3.039539 -3.412528 -1.795804 -4.800068 -4.187406 1.351726 1.374099 2.541081 2.557937 0.450356 3.727090 2.516319 3.737005 2.562564 4.646486 4.663820

-0.404806 0.073743 0.181731 -0.058663 0.242494 -1.061799 -2.160480 -0.364313 -2.552511 -2.703716 -0.753373 0.484378 -1.848885 -3.408444 -0.201830 -2.157392

-4.094138 -3.207191 -4.698996 -4.648793 -3.624659 -3.190943 -2.897806 -4.108483 -2.109873 -2.054731 -2.367478 -0.433298 0.318161 0.420637 1.157713 2.221367 1.097079 0.613009 -0.391362 1.259755 -3.603431 -0.566469 -0.627090 -0.758859 -0.559507 -0.094271 -1.784251 -0.565749 -0.526038 -1.471593 0.278004 -0.852389 -1.311488 -1.448202 -2.320580 -0.864843 -2.467721 -1.118147 -2.905361 -2.656192

2.838379 3.360900 2.557691 3.527170 1.634662 0.429884 0.741754 -0.176974 -0.380335 -1.385446 -0.493571 0.697629 -0.637771 -0.602178 -2.084947 -1.813115 -3.001685 -2.278424 -2.726191 -2.951156 1.634409 2.404595 2.449142 3.350237 4.404715 3.056684 3.286266 3.211444 4.296862 3.008217 2.945522 -1.410897 -0.662866 -2.651287 -1.150913 0.311583 -3.135810 -3.246811 -2.388882 -0.561913

CP3s C H H H C C H H C H H Co P P C H H C H H O C C C H H H C H H H C C C C H C H C H

0.409964 0.796238 1.280962 -0.232738 -0.364591 0.448154 1.462968 0.591110 -0.232333 0.208796 -1.293284 -0.045900 1.505200 -1.540522 0.657532 0.603230 1.259976 -0.755179 -0.741289 -1.335383 -1.584200 0.677018 -0.632869 -1.796609 -1.550841 -2.620943 -2.188402 1.916522 1.733866 2.507677 2.569555 2.674941 3.769853 2.417165 4.591258 3.975913 3.233905 1.565020 4.323281 5.443491

S49

H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

3.016975 4.962548 2.608037 3.769597 2.234224 4.539048 4.075693 3.000935 1.334672 4.155271 5.441761 2.699285 4.759088 -1.991865 -2.638276 -1.654394 -2.934965 -2.920948 -1.952527 -1.147755 -2.590901 -3.437386 -1.684025 -2.821902 -3.145184 -3.908793 -3.611730 -5.123549 -3.552503 -4.826409 -2.990269 -5.585578 -5.709457 -5.170580 -6.534100

-2.919510 -3.700680 1.658245 2.041644 2.364301 3.106165 1.495758 3.433087 2.054881 3.804523 3.393183 3.972550 4.636683 2.156214 3.011364 2.645493 4.323486 2.649159 3.957972 1.978210 4.799578 4.976911 4.323935 5.827075 -0.383815 -0.122478 -1.321805 -0.771374 0.588020 -1.970695 -1.566802 -1.692765 -0.560671 -2.706012 -2.202728

-4.102508 -2.767866 -0.042756 -0.724885 1.106251 -0.265065 -1.617978 1.563263 1.643040 0.878601 -0.802275 2.459762 1.236953 -0.184924 -1.085841 1.081623 -0.730933 -2.074945 1.439837 1.782247 0.533138 -1.442535 2.429709 0.809365 -0.965159 -2.109244 -0.035781 -2.310120 -2.856205 -0.237970 0.827261 -1.371856 -3.203614 0.487125 -1.533031

-1.568256 -1.030953 -1.173534 -2.636479 -1.314127 0.133549 0.779206 0.217800 0.621046 1.702504 0.104485 0.009627 1.610790 -1.365062 0.926919 0.924101 1.580155 -0.497831 -0.508873 -1.020823 -2.218923

-3.721601 -2.960481 -4.694539 -3.668375 -3.511270 -3.586262 -3.793028 -4.470145 -2.368753 -2.433148 -2.322221 -0.372676 0.329005 0.618685 1.494117 2.489038 1.556120 1.087617 0.194157 1.890394 -3.310407

3.410970 3.993456 3.732970 3.637186 1.939843 1.492549 2.357181 0.837373 0.720396 0.561804 -0.252462 0.632359 -0.644570 -0.704177 -1.935753 -1.468496 -2.816942 -2.288143 -2.929117 -2.827165 1.149904

TS2s C H H H C C H H C H H Co P P C H H C H H O

S50

C C C H H H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

0.412575 -0.817568 -1.991212 -1.744835 -2.491738 -2.742181 1.484199 1.628199 1.254818 2.448405 2.660608 3.737408 2.320252 4.461382 4.017139 3.045659 1.477969 4.118687 5.299761 2.771877 4.685311 2.878977 4.011213 2.687360 4.930042 4.177960 3.606882 1.804749 4.728680 5.807875 3.448924 5.449746 -1.952499 -2.933244 -1.359258 -3.306876 -3.419895 -1.730110 -0.606247 -2.704049 -4.074466 -1.260360 -2.998405 -2.907308 -3.426549 -3.580907 -4.597063 -2.914611 -4.749099 -3.155597 -5.261107 -4.989020 -5.246147 -6.171521

-1.042512 -0.530167 -0.267247 -0.234625 0.673646 -1.062005 -1.416829 -0.606003 -2.321667 -1.584405 -0.823258 -1.470207 -1.204582 -2.453570 -1.183617 -2.186427 -0.727849 -2.814176 -2.938506 -2.461193 -3.582933 1.378177 1.845155 1.752092 2.669289 1.548780 2.577818 1.377703 3.037108 3.025147 2.859987 3.680472 2.279544 3.005226 2.851494 4.274392 2.565481 4.123499 2.273306 4.836785 4.826206 4.555894 5.829491 -0.166266 0.018152 -1.016013 -0.628356 0.668039 -1.662268 -1.201091 -1.468064 -0.478657 -2.335803 -1.979218

2.303241 2.258465 3.116649 4.190176 2.849689 2.983979 3.260091 3.986827 3.845228 2.761120 -1.609696 -0.985422 -2.913437 -1.652022 0.030090 -3.582149 -3.416268 -2.953670 -1.154036 -4.599677 -3.475956 0.175904 -0.504032 1.509608 0.137822 -1.540591 2.152770 2.033852 1.467658 -0.399558 3.192766 1.969516 -0.141188 -0.827737 0.989202 -0.397479 -1.699738 1.420296 1.531391 0.726832 -0.938310 2.302584 1.063952 -1.297097 -2.585675 -0.413001 -2.974532 -3.295922 -0.802046 0.571542 -2.082962 -3.979648 -0.105878 -2.392174

-2.786859 -1.974291

3.527930 4.013791

CP4s C H

-2.434655 -1.878735

S51

H H C C H H C H H Co P P C H H C H H O C C C H H H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C

-2.470923 -3.458034 -1.732121 -0.230310 0.080477 0.047654 0.529207 1.603870 0.231554 -0.022023 1.659356 -1.274642 1.064510 1.086339 1.745600 -0.364668 -0.395312 -0.845465 -2.329538 0.260203 -0.834539 -1.712210 -1.239156 -2.026884 -2.633446 1.157268 0.955859 1.038909 2.218149 2.644384 3.655045 2.327165 4.333070 3.922690 3.004212 1.540659 4.009525 5.122337 2.746292 4.540081 2.982089 4.173778 2.768841 5.128676 4.356474 3.726115 1.836283 4.906332 6.051213 3.551117 5.655942 -1.837148 -3.029534 -1.000599 -3.374387 -3.699664 -1.338884 -0.086553 -2.529531

-3.616306 -2.468897 -3.240193 -3.414463 -3.572815 -4.302973 -2.192600 -2.424171 -2.158521 -0.340433 0.158396 0.562753 1.251371 2.276944 1.224381 0.872001 -0.069618 1.648631 -3.458258 -0.901610 -0.141057 0.744820 1.075660 1.634402 0.214975 -0.632152 0.347794 -1.387506 -0.649865 -1.130619 -1.817581 -1.542124 -2.873614 -1.505039 -2.599507 -1.030025 -3.269026 -3.388356 -2.899493 -4.095880 1.188673 1.483448 1.734852 2.309647 1.054741 2.560002 1.497119 2.849021 2.533661 2.975104 3.493675 2.283694 2.832271 3.084858 4.149455 2.221997 4.404852 2.642879 4.939251

4.247993 3.307868 2.274980 2.366024 3.409325 1.785890 1.804425 1.817355 0.704806 0.590636 -0.664800 -0.819471 -2.055807 -1.660661 -2.917779 -2.417861 -2.984392 -3.028840 1.236376 2.559198 2.178097 2.973565 3.913464 2.413777 3.264287 3.736949 4.187529 4.531271 3.443951 -1.525839 -0.836798 -2.825745 -1.436142 0.174337 -3.425716 -3.380309 -2.732891 -0.890070 -4.440279 -3.201644 0.089315 -0.584484 1.359038 -0.001146 -1.570575 1.945234 1.877879 1.265067 -0.535047 2.936908 1.721561 -0.431343 -0.916099 0.356457 -0.622662 -1.521710 0.640921 0.764196 0.153229

S52

H H H C C C C H C H C H H H

-4.310465 -0.677207 -2.801820 -2.821075 -3.323969 -3.510015 -4.487144 -2.805834 -4.670622 -3.102183 -5.161938 -4.864777 -5.173233 -6.064051

4.559100 5.014301 5.968152 -0.254298 -0.165258 -1.032054 -0.842907 0.437296 -1.709511 -1.135368 -1.616482 -0.769825 -2.332915 -2.156226

-0.999964 1.254939 0.383486 -1.356526 -2.661388 -0.420212 -3.017728 -3.408180 -0.775942 0.584986 -2.075970 -4.036834 -0.038065 -2.360156

-2.303013 -2.520141 -3.011378 -1.296321 -2.453275 -3.754823 -4.377772 -4.303702 -3.455721 -4.348431 -3.125435 -0.827251 -0.140472 0.544230 0.191157 -0.802680 0.762729 0.856758 1.941633 0.480691 -2.022918 -2.347903 -1.324777 -0.247065 -0.592986 0.618173 0.149008 -2.519121 -1.715895 -3.479875 -2.524745 1.443642 1.475176 2.638851 2.668863 0.550010 3.838535 2.644723 3.856234 2.676758 4.762388 4.793930

3.457305 3.801334 3.942384 3.780626 1.959308 1.347583 2.154471 0.909423 0.338951 0.125040 -0.621062 0.520534 -0.633177 -0.666312 -2.362444 -2.823732 -2.943987 -2.328527 -2.471989 -3.128613 1.478277 0.979813 1.446863 2.347466 2.999394 1.780472 3.001169 1.126820 1.711409 1.601836 0.142527 -0.056455 1.244016 -0.778195 1.796986 1.821470 -0.216323 -1.785520 1.069218 2.803832 -0.786813 1.508064

TS3s C H H H C C H H C H H Co P P C H H C H H O C C C H H H C H H H C C C C H C H C H H H

0.168861 1.186009 -0.518692 -0.115748 0.014202 0.558632 0.974594 -0.286278 1.664694 2.269878 1.229318 -0.019446 -1.689551 1.086936 -1.120822 -1.058478 -1.857307 0.254011 0.174269 0.902603 -1.128922 2.469212 1.726425 2.247614 3.065129 2.627520 1.458811 3.943804 4.406798 4.199562 4.438177 -2.403336 -2.931184 -2.320355 -3.378207 -2.976260 -2.753764 -1.904578 -3.285129 -3.793043 -2.670198 -3.622208

S53

C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

-3.147689 -4.437360 -2.944808 -5.504963 -4.606624 -4.012433 -1.943152 -5.293804 -6.505198 -3.846065 -6.130171 2.811241 3.929020 3.010635 5.214400 3.795372 4.290709 2.145934 5.398494 6.074819 4.426296 6.402488 1.180643 1.731965 0.566226 1.669788 2.217377 0.501181 0.113131 1.051525 2.102848 0.004967 0.997178

-1.214820 -0.704278 -2.598932 -1.563353 0.371341 -3.454521 -2.991633 -2.938485 -1.156487 -4.529797 -3.609589 0.180763 0.863796 -0.903380 0.485709 1.704340 -1.276724 -1.466989 -0.578850 1.030793 -2.117589 -0.870368 2.272167 3.325205 2.558751 4.632555 3.117034 3.866119 1.736493 4.904534 5.442699 4.074199 5.928960

-0.878234 -1.062812 -0.939757 -1.308689 -1.010610 -1.191609 -0.764634 -1.374465 -1.449331 -1.233508 -1.563786 -1.184936 -0.697960 -2.050813 -1.084585 -0.016994 -2.443149 -2.409301 -1.961159 -0.699373 -3.121747 -2.264892 -0.021722 -0.763712 1.201278 -0.291098 -1.719181 1.675567 1.760977 0.929097 -0.876255 2.622371 1.294467

-0.771819 -1.476803 -0.595096 0.183348 -1.299062 -2.640947 -3.350694 -2.521795 -3.125990 -4.220743 -2.877205 -0.488895 0.205650 0.209567 0.302257 -0.728206 0.866567 0.937280 2.013357 0.833637 -0.363077 -2.451919

4.367353 5.000358 4.828164 4.359845 2.960558 2.853213 3.594754 3.043384 1.439749 1.396860 0.709304 0.672834 -0.786626 -0.703428 -2.453990 -2.825427 -3.185128 -2.240115 -2.052337 -3.115225 2.149366 1.120711

CP5s C H H H C C H H C H H Co P P C H H C H H O C

-0.308934 0.246415 -1.288227 0.231755 -0.479463 -1.212216 -0.814780 -2.287549 -0.876076 -0.759466 -1.659081 -0.058192 -1.511754 1.452572 -0.716561 -0.621344 -1.312014 0.651779 0.534158 1.305989 -1.173474 0.454020

S54

C C H H H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

0.804909 2.180397 2.510353 2.917038 2.250470 1.415006 2.384427 1.600053 1.020454 -2.182528 -1.918131 -2.929011 -2.379892 -1.362822 -3.383104 -3.167953 -3.105280 -2.172427 -3.959052 -3.461387 -3.025585 -3.545387 -3.680733 -4.702071 -3.048449 -4.839112 -3.251169 -5.350677 -5.097139 -5.340850 -6.253368 2.895013 4.129025 2.722758 5.160973 4.282943 3.753870 1.762171 4.976422 6.114891 3.601731 5.782891 2.237863 3.239479 1.763899 3.758694 3.620485 2.281845 0.976403 3.280490 4.538664 1.904865 3.687545

-1.535638 -1.174669 -1.808825 -1.298871 -0.134255 -3.193444 -2.693355 -4.199030 -3.339205 1.903306 2.555806 2.562283 3.852844 2.021968 3.859881 2.052677 4.507626 4.352693 4.366955 5.523394 -0.786546 -1.117239 -1.236257 -1.887828 -0.774925 -1.997918 -0.992596 -2.327159 -2.144653 -2.345469 -2.930507 -0.681225 -0.720557 -1.477247 -1.528928 -0.107001 -2.283682 -1.479178 -2.314061 -1.543677 -2.893828 -2.947822 1.695575 2.424428 2.150942 3.580654 2.076408 3.309364 1.582163 4.024216 4.138999 3.652674 4.929448

2.143332 2.601956 3.442421 1.796354 2.947120 0.250365 0.158943 0.662833 -0.765123 -0.557520 0.651321 -1.541560 0.865005 1.424479 -1.329983 -2.476785 -0.126589 1.809947 -2.102751 0.037982 -1.021667 -2.277513 0.133700 -2.377847 -3.185657 0.028018 1.108737 -1.226945 -3.359673 0.929948 -1.307754 -1.409169 -0.746581 -2.548936 -1.215150 0.141491 -3.018847 -3.067336 -2.350865 -0.690261 -3.907769 -2.715047 0.044602 -0.608771 1.279893 -0.034829 -1.570041 1.853993 1.785253 1.197527 -0.550316 2.816121 1.645189

-0.592862 -0.264745 -0.265224

-2.522658 -3.535323 -1.764694

4.520176 4.753362 5.227304

CP1t C H H

S55

C H H C C H H H O Co P P C H H C H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C

-1.951562 -2.518738 -2.555429 -0.699517 -0.341589 -0.865173 0.739856 -0.611122 -0.380429 -0.024062 1.617007 -1.430724 -0.495299 -1.014286 -0.433006 0.894134 0.817951 1.566225 -1.958847 -2.667904 -1.601897 -3.001276 -2.972681 -1.932551 -1.075377 -2.629241 -3.556107 -1.650559 -2.890563 -2.973603 -3.449590 -3.700435 -4.630266 -2.896045 -4.884367 -3.321202 -5.350371 -4.988289 -5.439067 -6.271775 3.064300 4.300103 2.906253 5.354919 4.436865 3.957488 1.950341 5.184669 6.314955 3.822795 6.012161 2.376722 2.311037 3.020408 2.878731 1.817972 3.597192 3.065633 3.525099

-2.337242 -1.456095 -3.222736 -2.090465 -3.083829 -2.836973 -3.059396 -4.116092 -0.787507 -0.318702 0.170513 0.332139 0.580644 1.265132 -0.399055 1.109207 2.148538 1.123412 2.050098 2.844041 2.590633 4.156190 2.427016 3.905053 1.963884 4.688992 4.765139 4.313404 5.716069 -0.496194 -0.511855 -1.169266 -1.179231 -0.003397 -1.827127 -1.177369 -1.834654 -1.187786 -2.345021 -2.358340 1.217272 1.096140 2.195303 1.938970 0.331359 3.045456 2.277152 2.916007 1.832419 3.801751 3.572395 -1.310793 -1.612203 -2.216730 -2.784083 -0.929031 -3.378639 -1.998202 -3.667425

3.889473 4.180362 3.689612 3.083815 2.005426 1.064497 1.801643 2.266127 2.788413 1.030209 -0.384811 -0.576781 -2.167732 -2.853376 -2.663577 -1.823942 -1.472850 -2.693298 -0.198613 -1.106906 1.041686 -0.785636 -2.068662 1.363274 1.767426 0.447746 -1.497910 2.332205 0.696762 -1.101830 -2.418339 -0.110113 -2.733765 -3.208038 -0.425060 0.913976 -1.738166 -3.762238 0.355374 -1.987776 0.025308 -0.620201 1.014724 -0.282755 -1.385357 1.342550 1.536492 0.695752 -0.785700 2.113928 0.960030 -1.146642 -2.511343 -0.289092 -3.007668 -3.202070 -0.786465 0.779161 -2.148765

S56

H H H

2.817603 4.098720 3.967887

-3.003916 -4.066151 -4.582537

-4.072438 -0.107421 -2.537979

-0.559587 -1.344149 0.441764 -0.742035 0.089257 -1.722020 -0.723144 -2.111282 -2.211586 -2.272639 -2.900831 0.286363 0.052696 1.684524 -1.394233 -0.406646 -0.956042 -0.260034 0.945139 0.815908 1.609207 2.185790 1.492973 3.187953 1.795177 0.739900 3.486627 3.742498 2.786687 1.258054 4.268464 3.022007 3.294406 3.698491 4.146535 4.923400 3.058883 5.371713 3.838485 5.762928 5.223066 6.023377 6.720006 -2.756593 -4.088894 -2.442226 -5.079684 -4.351854 -3.434558 -1.405379 -4.758223 -6.109905 -3.171305

0.025518 0.008207 0.012406 1.004488 1.720205 1.479171 -0.848341 -1.394235 -1.766082 -2.240816 -0.657716 -1.414192 0.226540 0.144120 0.261303 0.055586 0.449811 -1.020725 0.736237 1.826717 0.526246 -1.556353 -2.647712 -1.777709 -3.941003 -2.470373 -3.069937 -0.931197 -4.153395 -4.786894 -3.233822 -5.164927 1.011327 1.986565 0.701762 2.635049 2.244731 1.341789 -0.051510 2.313920 3.391471 1.085203 2.820076 -0.934953 -0.611612 -2.270056 -1.588821 0.415071 -3.243158 -2.556798 -2.906146 -1.317523 -4.272009

4.276235 5.036439 4.707388 3.125609 3.040909 3.068908 3.094319 2.846256 1.821881 3.529025 3.036669 2.493865 1.287733 -0.227539 -0.427472 -1.997779 -2.863091 -2.163919 -1.826705 -1.762502 -2.677041 -0.716590 -0.179822 -1.669822 -0.604720 0.590886 -2.088866 -2.079002 -1.558725 -0.178010 -2.829110 -1.886518 -0.147881 -1.066844 0.923169 -0.919563 -1.909780 1.062977 1.650098 0.142382 -1.643393 1.896587 0.255368 -0.668010 -0.377271 -0.966276 -0.408046 -0.123398 -1.002842 -1.149915 -0.724852 -0.182339 -1.243017

TS1t C H H C H H C C H H H O Co P P C H H C H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H

S57

H C C C C H C H C H H H

-5.533971 -2.187313 -3.025524 -1.890371 -3.556120 -3.273818 -2.417193 -1.236096 -3.251301 -4.209312 -2.176725 -3.666040

-3.669318 1.888436 2.111701 2.960233 3.374236 1.282587 4.227539 2.789072 4.434877 3.533694 5.052423 5.423242

-0.748270 -0.751772 -1.852867 0.096130 -2.094289 -2.517391 -0.146529 0.953544 -1.241118 -2.950881 0.522052 -1.432052

2.066748 1.994792 3.137490 1.593970 1.423856 2.066085 2.531981 2.930440 1.144753 0.511061 1.751719 -0.039365 1.179175 -1.783151 0.136838 -0.146693 0.709123 -1.121009 -0.888509 -1.877081 0.407299 2.642178 3.931057 2.465850 5.010301 4.085999 3.546879 1.467408 4.823464 6.005173 3.389991 5.668934 1.830138 2.140593 1.978662 2.576417 2.041022 2.424040 1.726070 2.717630 2.809883 2.535260 3.058584 -3.358015

-4.388362 -5.119906 -4.234400 -4.799334 -3.097511 -2.291912 -2.997206 -1.813505 -1.224642 -1.685207 -0.469286 -0.660561 0.317689 -0.190214 0.531438 1.592059 0.298877 -0.325804 -1.387525 -0.032475 -2.696883 -0.592060 -0.308806 -1.707688 -1.112514 0.550907 -2.507116 -1.960032 -2.214819 -0.873200 -3.366963 -2.841837 1.998085 2.909029 2.394078 4.193115 2.611049 3.676193 1.681658 4.578585 4.895782 3.973063 5.583971 -1.112771

0.726197 1.541486 0.539541 -0.169564 1.134980 2.227463 2.944657 1.728585 2.810604 3.589078 3.329761 1.273414 -0.352543 -0.035453 -1.897300 -1.949653 -2.804786 -1.783504 -1.950219 -2.525174 0.556923 -0.965767 -0.491488 -1.798139 -0.846167 0.161350 -2.156035 -2.158629 -1.678901 -0.473374 -2.806300 -1.956384 -0.031701 -1.048505 1.303322 -0.736158 -2.092785 1.615791 2.092521 0.596175 -1.534680 2.657540 0.838188 -0.173449

CP2t C H H H C C H H C H H Co P P C H H C H H O C C C C H C H C H H H C C C C H C H C H H H C

S58

C C C H C H C H H H C C C C H C H C H H H

-4.595036 -3.301347 -5.747523 -4.657542 -4.454108 -2.339822 -5.682763 -6.701902 -4.392410 -6.584976 -2.263029 -3.146945 -1.592697 -3.351982 -3.678639 -1.783238 -0.898945 -2.664800 -4.043237 -1.236096 -2.816901

-0.578863 -2.455662 -1.359599 0.456823 -3.231146 -2.900712 -2.684562 -0.927312 -4.270049 -3.292694 1.582123 2.125874 2.446958 3.500596 1.464895 3.824566 2.023946 4.352107 3.911731 4.483045 5.428475

0.207265 -0.576329 0.162957 0.539735 -0.626180 -0.835613 -0.259030 0.460160 -0.946710 -0.294683 -0.054005 -0.995753 0.817510 -1.060810 -1.682181 0.743911 1.548761 -0.195664 -1.795089 1.416979 -0.257876

-4.359631 -4.719216 -4.368164 -5.045170 -2.956920 -1.991161 -2.483965 -1.988739 -0.603120 0.136670 -0.370404 -0.087430 1.742022 -1.069864 1.045723 1.639574 1.216346 -0.452915 -1.046990 -0.672732 -2.639289 -0.072320 -0.513695 -1.032834 -0.945363 -0.510412 -2.094810 0.334795 0.150526 -0.204770 1.402576 3.121794 4.440296 2.824364 5.435672

-3.523801 -3.334378 -4.612585 -3.077559 -2.998592 -3.188910 -2.790117 -4.283303 -2.612080 -3.261881 -2.677949 -0.884550 -0.495230 0.550697 -0.372633 0.358290 -1.343703 -0.027189 -0.927496 0.704878 -2.507656 -1.106671 0.067246 1.362937 1.471228 2.208069 1.480704 -2.228555 -2.021979 -3.146915 -2.450959 -1.672845 -1.394698 -2.953630 -2.360024

-0.618432 0.399605 -0.763638 -1.343596 -0.833486 0.312458 1.218846 0.494008 0.094750 0.600892 -0.980036 1.081342 -0.284336 -0.411614 -2.022648 -2.588757 -2.503393 -2.055070 -2.256886 -2.843310 -1.905089 3.005879 2.781085 3.250247 4.340992 2.780954 2.991178 3.868765 4.932790 3.602585 3.748394 -0.529949 -0.147137 -1.022620 -0.278426

CP3t C H H H C C H H C H H Co P P C H H C H H O C C C H H H C H H H C C C C

S59

H C H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

4.693807 3.820532 1.797514 5.132104 6.456626 3.569913 5.912181 2.587257 3.478822 2.262222 4.026237 3.753361 2.806405 1.557307 3.686669 4.719799 2.530874 4.109541 -0.853618 -1.601318 0.110231 -1.382822 -2.373504 0.330776 0.710834 -0.411095 -1.980064 1.091052 -0.238643 -2.891066 -3.626865 -3.568156 -5.010491 -3.111842 -4.955893 -2.988868 -5.677446 -5.573370 -5.472818 -6.761324

-0.413038 -3.913859 -3.202930 -3.619554 -2.121608 -4.899120 -4.371546 1.120784 1.654034 1.879383 2.919687 1.067084 3.147565 1.461836 3.669584 3.324316 3.733680 4.663571 2.373650 3.204311 2.965378 4.576970 2.766978 4.339401 2.348277 5.149509 5.204337 4.774888 6.224303 0.413059 0.810653 -0.105233 0.673352 1.224885 -0.228118 -0.423248 0.156123 0.972442 -0.633243 0.052518

0.251138 -1.154927 -1.292757 -0.786650 0.016507 -1.545416 -0.891810 -0.071033 -1.010993 1.057908 -0.826666 -1.889365 1.243403 1.779491 0.299848 -1.562554 2.119092 0.438191 -0.497993 0.348756 -1.324239 0.379010 0.983010 -1.294779 -1.991508 -0.439898 1.039228 -1.942029 -0.415917 -0.492013 -1.613917 0.616781 -1.632066 -2.481060 0.604693 1.486415 -0.522104 -2.514777 1.474015 -0.538027

-2.674755 -3.175745 -2.841164 -3.143043 -1.216079 -0.293271 -0.838425 -0.106460 0.972129 1.646322 1.519893 -0.022661 1.579671 -1.509856 0.755199 0.745512

-3.151658 -2.224486 -3.892842 -3.475543 -2.859825 -3.010994 -2.718931 -4.098225 -2.219191 -2.331307 -2.482941 -0.483716 -0.044642 0.266855 0.488600 1.587480

1.261080 1.573919 2.051528 0.326758 1.065061 2.246526 3.156669 2.349790 2.087162 2.939795 1.174067 0.989262 -0.563233 -0.603241 -2.157442 -2.146381

TS2t C H H H C C H H C H H Co P P C H

S60

H C H H O C C C H H H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

1.348606 -0.674954 -0.675615 -1.226958 -0.766710 0.490669 -0.789215 -1.785187 -2.695949 -1.412290 -2.121004 1.684044 1.616710 1.769952 2.619768 2.699315 3.883237 2.330726 4.686946 4.176878 3.135378 1.400315 4.317160 5.607327 2.835345 4.945465 2.751425 3.786865 2.582807 4.626469 3.940182 3.422033 1.784891 4.443792 5.427900 3.281477 5.103281 -1.710452 -0.975575 -2.525824 -1.039710 -0.352681 -2.596426 -3.116115 -1.849560 -0.456929 -3.234388 -1.902954 -3.210298 -3.501589 -4.245368 -4.790140 -2.713099 -5.529618 -4.036220 -5.808520 -4.998785 -6.318988 -6.814628

0.182844 -0.038692 -1.127529 0.416013 -2.540138 -0.216286 0.055477 0.934441 0.382837 1.431149 1.724549 0.056304 1.064087 -0.650643 -0.004059 -1.387263 -1.625430 -2.292216 -2.718965 -0.939448 -3.387791 -2.145664 -3.603715 -2.882208 -4.076996 -4.460994 1.338419 1.645253 2.134055 2.728309 1.022010 3.219971 1.881959 3.518719 2.957443 3.828601 4.365095 2.088911 2.857306 2.741325 4.248478 2.342684 4.130241 2.152404 4.885960 4.832957 4.627311 5.973200 -0.331628 -1.417975 0.203369 -1.941011 -1.869662 -0.323829 1.046277 -1.399667 -2.779478 0.108623 -1.812340

-3.029854 -2.233533 -2.379483 -3.068417 -0.045620 2.814699 2.701659 3.359578 3.638253 4.271339 2.670840 3.654069 4.090257 4.491230 3.081590 -1.093356 -0.379422 -2.097166 -0.680355 0.416693 -2.396698 -2.646625 -1.692270 -0.121688 -3.184655 -1.927189 -0.271853 -1.164963 0.865532 -0.926703 -2.046942 1.104682 1.566674 0.207812 -1.627532 1.996846 0.393026 -0.627209 0.281709 -1.561736 0.252004 1.016636 -1.587705 -2.265280 -0.683852 0.962637 -2.316948 -0.709493 -0.858650 -1.696152 -0.072948 -1.757097 -2.295676 -0.132612 0.587357 -0.975644 -2.420309 0.480498 -1.023175

S61

CP4t C H H H C C H H C H H Co P P C H H C H H O C C C H H H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C

-1.767331 -1.710408 -2.097130 -2.532808 -0.425962 0.770079 0.404131 1.227057 1.839432 2.636757 2.319897 -0.009649 1.351991 -1.741390 0.297962 0.167749 0.804346 -1.063574 -0.966355 -1.760878 -0.383473 1.258661 0.294874 -0.401805 -0.167539 -0.159901 -1.494595 1.821032 1.352930 1.703185 2.903531 2.716668 3.960186 2.484094 4.951060 4.158626 3.476875 1.527479 4.710317 5.916688 3.288853 5.487763 2.121807 2.421429 2.377324 2.957231 2.234593 2.914797 2.126597 3.202327 3.183079 3.102423 3.616825 -1.912154 -1.141310 -2.674028

-3.239695 -3.277883 -4.231089 -2.513187 -2.903533 -3.687512 -4.449912 -4.219477 -2.846354 -3.515959 -2.185844 -0.879260 0.280838 0.221921 0.984885 2.058480 0.883944 0.295667 -0.747342 0.804012 -2.435381 -2.030290 -1.124563 -0.295529 -0.565876 0.775187 -0.359584 -2.363474 -1.800354 -3.434993 -2.167956 -0.572891 0.019052 -1.890292 -0.689521 1.034767 -2.588298 -2.361429 -1.990998 -0.221549 -3.610272 -2.542621 1.750431 2.922007 1.704162 4.025991 2.973413 2.808926 0.797060 3.971602 4.932175 2.762569 4.837717 2.007053 2.532316 2.882666

1.133763 2.227242 0.778786 0.842737 0.528556 1.065428 1.769637 0.218046 1.776478 2.133281 1.031948 0.685822 -0.795137 -0.446115 -2.172509 -1.977118 -3.140159 -2.180946 -2.510092 -2.861397 -0.681736 2.919766 2.637243 3.674336 4.717249 3.567531 3.561655 4.272852 5.087053 4.499780 4.317905 -1.663439 -1.912025 -2.087037 -2.586543 -1.571023 -2.768263 -1.852439 -3.019972 -2.771985 -3.094097 -3.546083 -0.029948 -0.736536 1.347563 -0.079717 -1.809793 2.002686 1.904817 1.291121 -0.639452 3.074183 1.804450 -0.081804 0.960983 -0.868113

S62

C H C H C H H H C C C C H C H C H H H

-1.118109 -0.546417 -2.661689 -3.283125 -1.878946 -0.501262 -3.258952 -1.864590 -3.438726 -3.609569 -4.565381 -4.880379 -2.733901 -5.835323 -4.449126 -5.997609 -4.998130 -6.702180 -6.991487

3.902999 1.851844 4.249910 2.486260 4.761787 4.296173 4.921735 5.833658 -0.377687 -1.572082 0.250343 -2.103584 -2.099402 -0.288127 1.170367 -1.461821 -3.028900 0.214785 -1.880129

1.209462 1.574333 -0.613750 -1.681942 0.421933 2.016004 -1.228325 0.612696 -0.740180 -1.458034 -0.194763 -1.647993 -1.837028 -0.385190 0.377289 -1.116341 -2.209732 0.040682 -1.265580

-2.546331 -2.867156 -2.823171 -3.098318 -1.053579 -0.160943 -0.782434 0.291936 0.881060 1.363588 1.698450 -0.087699 1.588470 -1.465771 0.835349 0.830215 1.444214 -0.597476 -0.601009 -1.122343 -0.623207 0.112542 -0.856454 -1.949960 -2.202698 -1.703652 -2.869840 0.410522 -0.245962 0.319951 1.447905 2.784721 4.032802 2.398055 4.881126 4.348968 3.249761

-3.019359 -3.154453 -3.919462 -2.178322 -2.805883 -3.757659 -4.322361 -4.476483 -2.979361 -3.613658 -2.623305 -0.803951 0.086529 0.524139 1.038029 2.102310 0.933103 0.562356 -0.467578 1.199377 -2.550814 -1.838412 -1.302167 -0.393950 -0.543041 0.670715 -0.563777 -1.490322 -0.703090 -2.366759 -1.139618 -1.040455 -0.620981 -2.378086 -1.523338 0.413675 -3.274171

0.975952 2.015800 0.407000 0.540470 0.848197 1.661484 2.372266 0.964592 2.456820 3.214509 1.803219 0.518030 -0.646229 -0.651344 -2.074602 -1.800038 -2.981744 -2.299645 -2.683304 -3.025679 -0.372253 3.096033 2.320415 2.796151 3.858515 2.661037 2.217955 4.518359 4.905242 5.178787 4.631617 -1.459092 -1.934988 -1.620052 -2.568868 -1.797104 -2.263080

TS3t C H H H C C H H C H H Co P P C H H C H H O C C C H H H C H H H C C C C H C

S63

H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

1.428379 4.489092 5.853015 2.944232 5.155102 2.631258 3.182324 2.820076 3.901682 3.042829 3.544542 2.369159 4.084024 4.319355 3.679201 4.642292 -1.505183 -0.622920 -2.278895 -0.499415 -0.016973 -2.170096 -2.974352 -1.275769 0.204893 -2.779313 -1.186165 -3.185721 -3.448472 -4.259091 -4.750679 -2.625326 -5.559776 -4.070797 -5.810536 -4.937032 -6.381593 -6.828342

-2.702730 -2.850584 -1.190759 -4.312019 -3.555587 1.350518 2.458159 1.227826 3.417586 2.578958 2.182130 0.379729 3.281433 4.276072 2.073074 4.034715 2.317104 2.785762 3.244539 4.149175 2.065740 4.605615 2.893177 5.060266 4.495367 5.317292 6.126934 0.104210 -0.928994 0.665937 -1.368881 -1.413556 0.221365 1.459435 -0.795597 -2.170684 0.671823 -1.143962

-1.231715 -2.736239 -2.930705 -2.387287 -3.231506 0.178701 -0.477738 1.561704 0.230196 -1.552446 2.269459 2.083751 1.604455 -0.293470 3.344362 2.157699 -0.263176 0.717807 -0.973311 0.974319 1.273410 -0.705891 -1.736843 0.263366 1.729533 -1.261195 0.462708 -1.074756 -1.986613 -0.367623 -2.200352 -2.509408 -0.582066 0.356560 -1.500983 -2.913046 -0.027530 -1.667265

-2.751123 -3.189422 -2.541460 -3.502325 -1.472416 -0.413437 -0.901936 0.137918 0.467174 0.820671 1.383620 -0.159702 1.618432 -1.368964 0.924745 1.092526 1.453651 -0.571867

-3.701403 -4.250578 -4.419114 -2.994437 -2.974308 -3.915377 -4.663458 -4.452117 -3.010197 -3.510753 -2.687063 -0.762581 -0.068332 0.810721 0.816936 1.894281 0.514655 0.536484

0.295831 1.141152 -0.506865 -0.078786 0.679095 1.297035 1.939719 0.514695 2.162561 3.077400 1.636211 0.699271 -0.482313 -0.414625 -1.976351 -1.837194 -2.888931 -2.076758

CP5t C H H H C C H H C H H Co P P C H H C

S64

H H O C C C H H H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H C C C C H C H C H H H

-0.753729 -1.042703 -0.937636 -0.447927 -1.634254 -2.927057 -3.564839 -2.791936 -3.497776 -0.181683 -0.807668 -0.379845 0.868075 2.674307 4.042630 2.041213 4.769617 4.545222 2.775723 0.975916 4.137295 5.835334 2.280474 4.709352 2.796958 3.474366 2.995735 4.323867 3.338138 3.849971 2.455869 4.512820 4.840951 3.992295 5.175168 -1.047905 -0.199417 -1.499666 0.200107 0.161929 -1.111192 -2.162668 -0.256684 0.868767 -1.469537 0.052908 -3.137985 -3.571169 -4.089158 -4.925027 -2.839370 -5.443437 -3.769533 -5.864787 -5.248538 -6.172468 -6.924022

-0.519844 1.155093 -2.278390 -1.843447 -1.923032 -1.250842 -1.909074 -0.316207 -1.017441 -0.993044 -0.091848 -1.545030 -0.671619 -1.384784 -1.235894 -2.601431 -2.287319 -0.299708 -3.643526 -2.720457 -3.490436 -2.166266 -4.586462 -4.311417 1.140233 2.096809 1.126530 3.018357 2.122303 2.041947 0.392403 2.992696 3.758985 2.018741 3.715646 2.600370 2.977799 3.584224 4.303734 2.210469 4.910700 3.305316 5.270842 4.579738 5.667024 6.308342 0.678093 -0.509847 1.629259 -0.720994 -1.286739 1.410390 2.546863 0.238650 -1.647906 2.160248 0.069387

-2.319802 -2.853777 -0.413038 2.516067 1.804852 2.116767 2.728863 2.676652 1.210050 3.718550 3.735133 4.651486 3.768350 -1.193515 -1.446146 -1.490700 -1.998274 -1.202695 -2.050574 -1.258134 -2.304392 -2.187373 -2.279332 -2.734220 0.224863 -0.541362 1.610820 0.064809 -1.622887 2.218190 2.213511 1.444939 -0.543108 3.297319 1.917973 -0.183733 0.863242 -1.074315 1.015459 1.552770 -0.917725 -1.894700 0.124576 1.829249 -1.614478 0.239646 -0.827501 -1.439098 -0.439981 -1.678374 -1.668683 -0.680777 0.053718 -1.304239 -2.150373 -0.377093 -1.490466

S65

References (1) (2) (3) (4)

(5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22)

(23)

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Jia, K.; Zhang, F.; Huang, H.; Chen, Y. J. Am. Chem. Soc. 2016, 138, 1514. Ren, S.; Feng, C.; Loh, T.-P. Org. Biomol. Chem. 2015, 13, 5105. He, X.-P.; Shu, Y.-J.; Dai, J.-J.; Zhang, W.-M.; Feng, Y.-S.; Xu, H.-J. Org. Biomol. Chem. 2015, 13, 7159. Merck Sharp & Dohme Corp.; L. Tong, W. Yu, J. A. Kozlowski, L. Chen, O. Selyutin, S. H. Kim, M. Dwyer, B. Hu, B. Zhong, D. Wai, J. Hao, C. Shen, Z. Lei, W. Wang, WO2014/110706 A1, 2014. Limbach, M.; Dalai, S.; de Meijere, A. Adv. Synth. Catal. 2004, 346, 760. de Meijere, A.; Kozhushkov, S. I.; Spaeth, T.; Zefirov, N. S. J. Org. Chem. 1993, 58, 502. Lorenz, J. C.; Long, J.; Yang, Z.; Xue, S.; Xie, Y.; Shi, Y. J. Org. Chem. 2004, 69, 327. Nomura, K.; Matsubara, S. Chem. Asian J. 2010, 5, 147. Zhao, J.; Yu, Y.; Ma. S. Chem. Eur. J. 2010, 16, 74. Fürstner, A.; Mathes, C. Org. Lett. 2001, 3, 221. Najera, C.; Gil-Molto, J.; Karlström, S.; Falvello, L. R. Org. Lett. 2003, 5, 1451. Roesch, K. R.; Larock, R. C. J. Org. Chem. 2001, 66, 412. Urgaonkar, S.; Verkade, J. G. J. Org. Chem. 2004, 69, 5752. Tan, B.-H.; Dong, J.; Yoshikai, N. Angew. Chem. Int. Ed. 2012, 51, 9610. Huang, L.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Angew. Chem. Int. Ed. 2016, 55, 4808. Stuedemann, T.; Ibrahim-Ouali, M.; Knochel, P. Tetrahedron 1998, 54, 1299. Tellitu, I.; Serna, S.; Herrero, M. T.; Moreno, I.; Dominguez, E.; SanMartin, R. J. Org. Chem. 2007, 72, 1526. Deponti, M.; Kozhushkov, S. I.; Yufit, D. S.; Ackermann, L. Org. Biomol. Chem. 2013, 11, 142. Huang, M.; Feng, Y.; Wu, Y. Tetrahedron 2012, 68, 376. Faulkner, A.; Race, N. J.; Scott, J. S.; Bower, J. F. Chem. Sci. 2014, 5, 2416. (a) Zimmerman, H. E.; Ausen, S. M. J. Org. Chem. 1978, 43, 1493. (b) Zhou, S.; Yan, B.; Liu, Y. J. Org. Chem. 2005, 70, 4006. Piou, T.; Romanov-Michailidis, F.; Romanova-Michaelides, M.; Jackson, K. E.; Semakul, N.; Taggart, T. D.; Newell, B. S.; Rithner, C. D.; Paton, R. S.; Rovis, T. J. Am. Chem. Soc. 2017, 139, 1296 CCDC 1826866 (8) contains the supplementary crystallographic data for this paper. These data are provided free of charge by The Cambridge Crystallographic Data Centre. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;

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S67

NMR Spectra a

1H

NMR, CDCl3, 400 MHz

b

13C

NMR, CDCl3, 100 MHz

Figure S11. Characterization of 1k. a 1H NMR spectrum. b 13C NMR spectrum. S68

a

O Bu

Ph Bu 3a 1H

NMR, CDCl3, 400 MHz

b

O Bu

Ph Bu 3a 13C

NMR, CDCl3, 100 MHz

Figure S12. Characterization of 3a. a 1H NMR spectrum. b 13C NMR spectrum. S69

O Ph

H

H2 C

CH2

C H2

Figure S13. 1H-1H NOESY spectrum of 3a.

S70

a

O Bu Bu

Me

3b

1H

NMR, CDCl3, 400 MHz

b

O Bu Me 13C

Bu 3b NMR, CDCl3, 100 MHz

Figure S14. Characterization of 3b. a 1H NMR spectrum. b 13C NMR spectrum. S71

a

O Bu Bu

MeO

3c

1H

NMR, CDCl3, 400 MHz

b

O Bu MeO

13C

Bu 3c

NMR, CDCl3, 100 MHz

Figure S15. Characterization of 3c. a 1H NMR spectrum. b 13C NMR spectrum. S72

a

O Bu Bu

F 1H

3d NMR, CDCl3, 400 MHz

b

O Bu F 13C

Bu 3d NMR, CDCl3, 100 MHz

Figure S16. Characterization of 3d. a 1H NMR spectrum. b 13C NMR spectrum. S73

a

O

O Bu Bu

Cl

Bu

+

Bu

3e 1H

3a

NMR, CDCl3, 400 MHz

b

O

O Bu Bu

Cl

3e

13C

Bu

+

Bu 3a

NMR, CDCl3, 100 MHz

Figure S17. Characterization of 3e. a 1H NMR spectrum. b 13C NMR spectrum. S74

a

O Bu Bu OMe 1H

3f

NMR, CDCl3, 400 MHz

b

O Bu Bu OMe

13C

3f

NMR, CDCl3, 100 MHz

Figure S18. Characterization of 3f. a 1H NMR spectrum. b 13C NMR spectrum. S75

a

O Bu Bu CF3 1H

3g

NMR, CDCl3, 400 MHz

b

O Bu Bu

CF3 13C

3g 3ga

NMR, CDCl3, 100 MHz

Figure S19. Characterization of 3g. a 1H NMR spectrum. b 13C NMR spectrum. S76

a

O Bu Bu

OMe 3h 1H

NMR, CDCl3, 400 MHz

b

O Bu OMe

Bu

3h 13C

NMR, CDCl3, 100 MHz

Figure S20. Characterization of 3h. a 1H NMR spectrum. b 13C NMR spectrum. S77

a

O S

Bu Bu 3i

1H

NMR, CDCl3, 400 MHz

b

O S

Bu Bu 3i

13C

NMR, CDCl3, 100 MHz

Figure S21. Characterization of 3i. a 1H NMR spectrum. b 13C NMR spectrum. S78

a

O Bn

Bu Bu 3j

1H

NMR, CDCl3, 400 MHz

b

O Bn

Bu Bu 3j

13C

NMR, CDCl3, 100 MHz

Figure S22. Characterization of 3j. a 1H NMR spectrum. b 13C NMR spectrum. S79

a

O Bu

n-C10H21 Bu 3k

1H

NMR, CDCl3, 400 MHz

b

O Bu

n-C10H21 Bu 3k

13C

NMR, CDCl3, 100 MHz

Figure S23. Characterization of 3k. a 1H NMR spectrum. b 13C NMR spectrum. S80

a

O Bu Bu 3l 1H

NMR, CDCl3, 400 MHz

b

O Bu Bu 3l 13C

NMR, CDCl3, 100 MHz

Figure S24. Characterization of 3l. a 1H NMR spectrum. b 13C NMR spectrum. S81

a

O Bu Bu 3m

1H

NMR, CDCl3, 400 MHz

b

O Bu Bu 3m 13C

NMR, CDCl3, 100 MHz

Figure S25. Characterization of 3m. a 1H NMR spectrum. b 13C NMR spectrum. S82

a

O Bu Bu 3n 1H

NMR, CDCl3, 400 MHz

b

O Bu Bu 3n 13C

NMR, CDCl3, 100 MHz

Figure S26. Characterization of 3n. a 1H NMR spectrum. b 13C NMR spectrum. S83

210

200

13C

190

180

Me

170

160

150 6.5

140 6.0

130 5.5

120 5.0 4.5

110

S84

100 4.0

90 3.5

80

3.0

70

2.5

60

2.0

50

1.5

40

30

Figure S27. Characterization of 3o. a 1H NMR spectrum. b 13C NMR spectrum. 6.45

7.0 8.45 3.29

7.5

5.24

8.0

40.73 39.06 32.13 30.69 29.83 27.42 22.79 22.32 17.04 14.03 13.98

8.5 1.01

9.0 1.01

9.5 1.03

Me

1.01 2.01

2.02

1H

136.86 136.39 132.73 128.57 128.22 127.61

204.43

7.956 7.938 7.934 7.566 7.552 7.547 7.542 7.532 7.529 7.526 7.478 7.458 7.444 7.440 7.260 5.147 5.129 5.111 3.650 3.633 3.615 3.598 2.554 2.538 2.518 2.505 2.071 2.055 2.038 2.019 2.003 1.983 1.961 1.949 1.935 1.915 1.346 1.333 1.323 1.317 1.311 1.306 1.297 1.278 1.266 1.250 1.240 1.232 1.225 1.215 1.166 1.149 0.916 0.899 0.882 0.863 0.856 0.846 0.828

a JF08-427H, AV400

O

Bu Bu

3o

NMR, CDCl3, 400 MHz

1.0 0.5

20

ppm

b JF08-427C, AV400

O

Bu Bu

3o

NMR, CDCl3, 100 MHz

ppm

a

O

O

Ph

Ph +

Et

Ph

Et

Ph

3p

3p’ (9:1)

1H

NMR, CDCl3, 400 MHz

b

O

O

Ph

Ph +

Et

Ph

Et

Ph

3p

3p’ (9:1)

13C

NMR, CDCl3, 100 MHz

Figure S28. Characterization of 3p. a 1H NMR spectrum. b 13C NMR spectrum. S85

a

O

O

Ph

Ph

+

Me

Ph

Me 3q

Ph 3q’ (9:1)

1H

NMR, CDCl3, 400 MHz

b

O

O

Ph

Ph

+

Me 3q

Me

Ph Ph 3q’

(9:1) 13C

NMR, CDCl3, 100 MHz

Figure S29. Characterization of 3q. a 1H NMR spectrum. b 13C NMR spectrum. S86

O Ph

H2 C

H

CH3

Figure S30. 1H-1H NOESY spectrum of 3q.

S87

a

O

O

Ph

Ph

Ph

+

Bu

Ph Bu

3r

3r’ (7:1)

1H

NMR, CDCl3, 400 MHz

b

O

O

Ph

Ph Bu

+

Ph

3r

Ph Bu 3r’

(7:1) 13C

NMR, CDCl3, 100 MHz

Figure S31. Characterization of 3r. a 1H NMR spectrum. b 13C NMR spectrum. S88

a

O O

Bu

Ph

Ph

+ Bu 3s

OMe

3s’ OMe

(8:1) 1H

NMR, CDCl3, 400 MHz

b

O O + Bu 3s

OMe (8:1)

13C

Bu

Ph

Ph

3s’ OMe

NMR, CDCl3, 100 MHz

Figure S32. Characterization of 3s. a 1H NMR spectrum. b 13C NMR spectrum. S89

a

O O Bu

Ph Ph

+

Bu 3t

CO2Et

3t’ CO2Et

(14:1) 1H

NMR, CDCl3, 400 MHz

b

O O Bu

Ph Ph

+

Bu 3t 13C

CO2Et

NMR, CDCl3, 100 MHz

(14:1)

3t’ CO2Et

Figure S33. Characterization of 3t. a 1H NMR spectrum. b 13C NMR spectrum. S90

a

O O

Bu

Ph

Ph

+ Bu 3u

Ph

3u’ Ph

(8:1) 1H

NMR, CDCl3, 400 MHz

b

O O + Bu 3u 13C

Bu

Ph

Ph Ph

(8:1)

3u’ Ph

NMR, CDCl3, 100 MHz

Figure S34. Characterization of 3u. a 1H NMR spectrum. b 13C NMR spectrum. S91

a

O O

Bu

Ph

Ph

+ Bu

Cl

3v

3v’ Cl

(11:1) 1H

NMR, CDCl3, 400 MHz

b

O O

Bu

Ph

Ph

+ Bu 3v

Cl (11:1)

13C

3v’ Cl

NMR, CDCl3, 100 MHz

Figure S35. Characterization of 3v. a 1H NMR spectrum. b 13C NMR spectrum. S92

a

O

O

Bu

Ph

Ph

+

Bu 3w

3w’

CF3

CF3

(17:1) 1H

NMR, CDCl3, 400 MHz

b

O

O +

Bu 3w

3w’

CF3 (17:1)

13C

Bu

Ph

Ph

CF3

NMR, CDCl3, 100 MHz

Figure S36. Characterization of 3w. a 1H NMR spectrum. b 13C NMR spectrum. S93

a

O Me

O

Ph Ph

+

n-C6H13 Me

n-C6H13 3x 1H

3x’

(3:1)

NMR, CDCl3, 400 MHz

b

O Me

O

Ph Ph

+

n-C6H13 Me

n-C6H13 3x 13C

(3:1)

3x’

NMR, CDCl3, 100 MHz

Figure S37. Characterization of 3x. a 1H NMR spectrum. b 13C NMR spectrum. S94

a

O O

OMe

Ph

Et

Ph +

MeO

Et 3y 1H

3y’

(6:1)

NMR, CDCl3, 400 MHz

b

O O

OMe

Ph

Et

Ph +

MeO

Et 3y

13C

(6:1)

3y’

NMR, CDCl3, 100 MHz

Figure S38. Characterization of 3y. a 1H NMR spectrum. b 13C NMR spectrum. S95

a

O

Me

O

Et

+

Me

Me

3z

3z’

(9:1) 1H

Et Me

Ph

Ph

NMR, CDCl3, 400 MHz

b

O

Me

O

Ph

Ph Et

+

Me

Et Me

Me

3z (9:1) 13C NMR, CDCl , 100 MHz 3

3z’

Figure S39. Characterization of 3z. a 1H NMR spectrum. b 13C NMR spectrum. S96

a

O Ph

Ph BnO 3aa

1H

NMR, CDCl3, 400 MHz

b

O Ph

Ph BnO 3aa

13C

NMR, CDCl3, 100 MHz

Figure S40. Characterization of 3aa. a 1H NMR spectrum. b 13C NMR spectrum. S97

a

O

O

Ph EtO2C

Ph + Ph 3ab

1H

CO2Et Ph 3ab’

(5:1)

NMR, CDCl3, 400 MHz

b

O

O

Ph EtO2C

Ph + Ph 3ab

13C

CO2Et Ph

(5:1)

3ab’

NMR, CDCl3, 100 MHz

Figure S41. Characterization of 3ab. a 1H NMR spectrum. b 13C NMR spectrum. S98

a

O

O

Ph

Ph +

Ph Ph

3ac 1H

(5:1)

3ac’

NMR, CDCl3, 400 MHz

b

O

O

Ph

Ph +

Ph Ph

3ac 13C

(5:1)

3ac’

NMR, CDCl3, 100 MHz

Figure S42. Characterization of 3ac. a 1H NMR spectrum. b 13C NMR spectrum. S99

a

O

O

Bu

Ph

S

Ph

+ S

Bu 3ad

3ad’ (11:1)

1H

NMR, CDCl3, 400 MHz

b

O

O S

Ph

Bu

Ph + S

Bu 3ad’

3ad (11:1) 13C

NMR, CDCl3, 100 MHz

Figure S43. Characterization of 3ad. a 1H NMR spectrum. b 13C NMR spectrum. S100

a

O

O Ph

Ph n-C6H13 3ae

Ph

n-C6H13

+ 3ae’ Ph

(11:1) 1H

NMR, CDCl3, 400 MHz

b

O

O Ph

Ph n-C6H13 3ae

Ph

n-C6H13

+ 3ae’ Ph

(11:1) 13C

NMR, CDCl3, 100 MHz

Figure S44. Characterization of 3ae. a 1H NMR spectrum. b 13C NMR spectrum. S101

a

O Ph

Ph Ph 3af

1H

NMR, CDCl3, 400 MHz

b

O Ph

Ph Ph 3af

13C

NMR, CDCl3, 100 MHz

Figure S45. Characterization of 3af. a 1H NMR spectrum. b 13C NMR spectrum. S102

a

Ph OH Bu Bu 4a 1H

NMR, CDCl3, 400 MHz

b

Ph OH Bu Bu 4a 13C

NMR, CDCl3, 100 MHz

Figure S46. Characterization of 4a. a

1

H NMR spectrum. b

S103

13

C NMR spectrum.

13C

200

190

180

170

160

150

140 6.0

130 5.5

120 5.0

110 4.5

100

S104 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

30

Figure S47. Characterization of 4b. a 1H NMR spectrum. b 13C NMR spectrum. 3.12 3.08

6.5 4.45

7.0

4.27

7.5 2.05

8.0 4.15

8.5

42.77 32.40 32.25 30.31 28.89 25.21 23.21 22.88 21.00 14.06 13.82

9.0 1.09 5.49

9.5

89.76

1H

128.66 125.00

144.07 141.31 140.20 135.78

2.19 2.00

7.254 7.234 7.126 7.106 2.435 2.424 2.415 2.346 2.330 2.295 2.289 2.279 2.257 2.246 2.236 2.225 2.200 2.181 2.172 2.161 2.154 2.135 2.130 2.118 2.109 2.097 2.086 2.013 1.731 1.721 1.708 1.575 1.475 1.470 1.455 1.436 1.418 1.384 1.367 1.348 1.328 1.255 1.249 1.235 1.223 1.207 1.189 1.172 1.155 1.140 1.128 1.114 0.962 0.944 0.926 0.802 0.784 0.766 0.000

a JF08-359H, AV400

Me

OH Bu

4b Bu

NMR, CDCl3, 400 MHz

1.0 0.5

20

ppm

b JF08-359C, AV400

Me

OH Bu

4b Bu

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170

160

150

140

130

120

110 4.5

100

S105 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

40

4.29 3.10 3.09

5.0 4.24

5.5 2.05

6.0 1.08

6.5

42.82 32.31 32.21 30.28 28.86 25.09 23.18 22.86 14.04 13.78

7.0

5.34

7.5

1.06

8.0

89.45

8.5

114.70 114.49

9.0

126.78 126.70

9.5 2.00

2.02

1H

142.71 142.68 141.67 140.09

162.76 160.33

7.342 7.337 7.329 7.320 7.312 7.307 7.258 7.003 6.981 6.965 6.959 2.451 2.440 2.430 2.356 2.342 2.284 2.274 2.251 2.240 2.230 2.219 2.196 2.177 2.155 2.135 2.123 2.115 2.102 2.090 1.998 1.990 1.725 1.701 1.579 1.472 1.467 1.453 1.434 1.415 1.382 1.364 1.345 1.327 1.214 1.197 1.181 1.164 1.146 1.086 1.071 1.066 0.964 0.946 0.928 0.796 0.778 0.760 0.000

a JF08-360H, AV400

F

OH Bu

4d Bu

NMR, CDCl3, 400 MHz

1.5 1.0

30

Figure S48. Characterization of 4d. a 1H NMR spectrum. b 13C NMR spectrum. 0.5

20

ppm

b JF08-360C, AV400

F

OH

Bu

4d

Bu

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170

160

150 6.5

140 6.0

130 5.5

120 5.0

110 4.5

100

S106 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

30

Figure S49. Characterization of 4e. a 1H NMR spectrum. b 13C NMR spectrum. 3.08 3.02

7.0 4.22

7.5 4.15

8.0 2.00

8.5

42.79 32.31 32.26 30.27 28.85 25.10 23.17 22.86 14.04 13.79

9.0 1.05 1.11 4.14 1.03

9.5

89.47

1H

132.03 128.02 126.64

145.58 141.96 139.92

4.13

7.312 7.306 7.296 7.290 7.276 7.270 7.258 7.254 2.457 2.446 2.436 2.359 2.344 2.271 2.261 2.238 2.227 2.217 2.206 2.195 2.176 2.155 2.133 2.120 2.111 2.098 2.086 2.077 1.996 1.988 1.711 1.695 1.572 1.472 1.466 1.451 1.445 1.433 1.414 1.381 1.363 1.344 1.325 1.216 1.205 1.199 1.183 1.165 1.148 1.096 1.082 0.963 0.945 0.927 0.800 0.783 0.765 0.000

a JF08-361H, AV400

Cl

OH Bu

4e Bu

NMR, CDCl3, 400 MHz

1.0 0.5

20

ppm

b JF08-361C, AV400

Cl

OH Bu

4e Bu

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170

160

OMe

OH Bu

4f Bu

NMR, CDCl3, 100 MHz

150

140

130

120

110

100

S107

13C

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

30

Figure S50. Characterization of 4f. a 1H NMR spectrum. b 13C NMR spectrum. 3.09 3.06

4.0 4.39

4.5 4.15

5.0 2.06

5.5 4.19

6.0

42.67 32.37 32.31 30.29 28.86 25.21 23.20 22.87 14.05 13.81

6.5 1.04 2.23

7.0

55.17

7.5 3.12

8.0

89.81

8.5

117.61 111.69 110.91

9.0

128.94

9.5

141.56 140.06

1.17 1.00 1.01 1.00

1H

148.92

159.47

7.256 7.239 7.219 7.199 6.972 6.967 6.962 6.934 6.914 6.767 6.763 6.761 6.747 6.742 3.803 2.365 2.351 2.310 2.301 2.278 2.267 2.257 2.206 2.187 2.167 2.155 2.137 2.133 2.121 2.113 2.100 1.751 1.477 1.473 1.458 1.439 1.421 1.388 1.370 1.352 1.349 1.331 1.258 1.247 1.222 1.210 1.193 1.176 1.158 1.143 1.131 0.961 0.943 0.925 0.802 0.785 0.767 -0.000

a JF08-363H, AV400

OMe NMR, CDCl3, 100 MHz

OH Bu

4f Bu

NMR, CDCl3, 400 MHz

1.0 0.5

20

ppm

b JF08-363C, AV400

ppm

13C

190

180

170

160

150

140

130 5

120

110 4

100

S108

90 3

80

70

60

50

4.19 3.30 1.07 3.12 3.10

6

32.28 32.23 30.22 28.83 25.03 23.09 22.83 14.00 13.70

7 2.03

8

42.78

9 1.05 1.11 4.20 1.06

1.00 1.01 1.01 1.05

1H

89.50

148.07 142.44 139.79 130.76 130.44 130.12 129.81 128.60 128.45 128.35 125.74 123.24 123.20 123.17 123.13 123.03 122.11 122.07 122.03 122.00 120.33

7.670 7.543 7.524 7.482 7.463 7.433 7.414 7.395 7.258 2.475 2.464 2.400 2.385 2.303 2.292 2.269 2.258 2.248 2.237 2.221 2.202 2.193 2.183 2.174 2.166 2.153 2.144 2.132 2.119 2.110 2.006 1.997 1.748 1.710 1.563 1.488 1.483 1.468 1.449 1.431 1.392 1.374 1.356 1.353 1.335 1.197 1.184 1.181 1.168 1.151 1.134 0.969 0.951 0.933 0.777 0.760 0.742 0.000

a JF08-364H BBFO1

CF3

OH Bu

4g Bu

NMR, CDCl3, 400 MHz

2 1

40

30

Figure S51. Characterization of 4g. a 1H NMR spectrum. b 13C NMR spectrum. 0 ppm

b JF08-364C BBFO1

CF3

OH Bu

4g Bu

NMR, CDCl3, 100 MHz

20

ppm

13C

200

190

180

170

160

Bn OH

150

140 6.0

130 5.5

120 5.0

110 4.5

100

S109 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

30

Figure S52. Characterization of 4h. a 1H NMR spectrum. b 13C NMR spectrum. 6.55

6.5 2.88 4.17 4.66

7.0 1.05

7.5 6.07

8.0

44.79 37.30 33.27 31.48 30.01 28.79 24.90 23.49 22.80 14.03

8.5 1.03

9.0 1.00

9.5

87.81

1H

140.69 139.15 137.89 130.33 127.93 126.20

5.55

2.969 2.936 2.761 2.728 2.162 2.153 2.136 2.122 2.108 2.099 2.087 2.062 2.047 2.027 2.016 1.798 1.785 1.776 1.758 1.740 1.719 1.559 1.546 1.529 1.524 1.510 1.496 1.435 1.420 1.414 1.406 1.402

7.257 7.243 7.226 7.213 7.209 7.206

a JF08-311H, AV400

Bn OH Bu

4h Bu

NMR, CDCl3, 400 MHz

1.0 0.5

20

ppm

b JF07-989C BBFO1

Bu

4h Bu

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170

160 7.0

150 6.5

140 6.0

130 5.5

120 5.0

110 4.5

100

S110 4.0

90 3.5

80 3.0

70

2.5

60

50

1.05 2.02

7.5

41.23 36.43 33.08 30.68

8.0 1.00

8.5 1.08

9.0 2.21

9.5 2.05

7.75 8.38

1H

88.34

142.40 142.27 140.08 136.76 136.48 129.71 128.46 128.36 128.31 128.25 127.90 127.17 125.75

2.922 2.912 2.902 2.893 2.880 2.770 2.756 2.737 2.724 2.707 2.692 2.680 2.661 2.650 2.628 2.616 2.502 2.488 2.482 2.468 2.453 2.435 2.201 2.184 2.167 2.151 2.132 1.970 1.956 1.937 1.924 1.907 1.893 1.849

7.297 7.279 7.262 7.247 7.223 7.204 7.150 7.136 7.087 7.068

a JF08-916H AV400

Ph OH Ph

4i Ph

NMR, CDCl3, 400 MHz

2.0 1.5

40

1.0

30

Figure S53. Characterization of 4i. a 1H NMR spectrum. b 13C NMR spectrum. 0.5

20 ppm

b JF08-916C AV400

Ph OH Ph

Ph

4i

NMR, CDCl3, 100 MHz

ppm

146.85 145.42 140.61 135.64 129.21 128.16 127.99 126.81 126.52 124.99

9.5

220 9.0

13C

210 8.5

200

190 8.0

180 7.5

170 7.0

160 6.5

150 6.0

140

130 5.5

120 5.0

b JF08-133C-redo, AV400

Ph OH Ph

Et

4j

NMR, CDCl3, 100 MHz

110 4.0

100

90

S111

80

70

60

50

2.0

40

1.5 1.0

30

Figure S54. Characterization of 4j. a 1H NMR spectrum. b 13C NMR spectrum.

20 12.95

3.13

2.5

22.94

3.0

32.15

42.91

3.5 4.30 1.00

4.5

89.49

1H

2.14

2.11 2.02 4.01 2.00

2.609 2.598 2.589 2.578 2.562 2.544 2.520 2.349 2.342 2.337 2.330 2.324 2.321 2.319 2.304 2.298 2.288 2.280 2.271 2.262 2.243 2.225 2.123 1.123 1.104 1.085 0.000

7.406 7.403 7.385 7.382 7.298 7.279 7.276 7.260 7.200 7.182 7.170 7.167 7.164 7.156 7.152 7.149 7.144 6.997 6.993 6.981 6.977 6.974

a JF08-133H-redo, AV400

Ph OH Ph

4j Et

NMR, CDCl3, 400 MHz

0.5

10

ppm

ppm

210 9.0

200 8.5

13C

190 8.0

180 7.5

Ph OH

170

160 2.17

9.5 7.0 6.5

150

140 6.0

130 5.5

120 89.53

5.0

110 4.5

100

S112 4.0

b JF08-372C, AV400

Ph

4k Me

NMR, CDCl3, 100 MHz

90 3.0 2.5

80

70

60

50

1.5

40 15.88

0.95 3.13

2.0

35.44

43.15

3.5 1.98

1H

146.89 141.00 140.04 135.54 129.15 128.13 127.97 126.70 126.48 125.00

2.02 2.12 4.07 2.00

30

Figure S55. Characterization of 4k. a 1H NMR spectrum. b 13C NMR spectrum. 0.000

2.607 2.594 2.589 2.587 2.575 2.568 2.565 2.548 2.530 2.506 2.353 2.342 2.335 2.324 2.315 2.099 1.891

7.405 7.401 7.383 7.381 7.304 7.299 7.285 7.266 7.253 7.207 7.204 7.187 7.169 7.162 7.157 7.153 7.147 7.140 7.122 7.040 7.035 7.030 7.019 7.016

a JF08-372H, AV400

Ph OH Ph

Me

4k

NMR, CDCl3, 400 MHz

1.0 0.5

20 ppm

ppm

13C

210

200

190

180

170

160

150

140

130

120 4

110

100

S113 3

90

80 2

70

60

1

50

40

30

Figure S56. Characterization of 4l. a 1H NMR spectrum. b 13C NMR spectrum.

20

13.96

5 3.12

6

32.62 30.39 29.54 22.81

7

1.96 2.12

8

42.87

9 1.94 1.98 2.24 1.00

1H

2.605 2.594 2.585 2.573 2.565 2.547 2.359 2.350 2.348 2.341 2.333 2.330 2.313 2.276 2.261 2.242 2.222 2.203 2.194 2.188 2.061 1.543 1.517 1.513 1.498 1.477 1.458 1.362 1.344 1.326 1.307

JF08-373H,

89.50

146.86 144.19 141.19 135.66 129.29 128.13 127.94 126.76 126.49 124.98

2.19 2.89 3.89 1.99

7.407 7.403 7.385 7.383 7.376 7.309 7.290 7.287 7.271 7.256 7.212 7.193 7.182 7.179 7.175 7.163 7.158 6.988 6.983 6.968 6.964

a BBF02

Ph OH Ph

Bu

4l

NMR, CDCl3, 400 MHz

0 ppm

b JF08-326C, AV400

Ph OH Ph

Bu

4l

NMR, CDCl3, 100 MHz

ppm

13C

200

190

Ph OH

180

170

160

150

140

130

120

110 4.5

100

S114 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

1.0

30

Figure S57. Characterization of 4m. a 1H NMR spectrum. b 13C NMR spectrum.

20

14.31 13.91

5.0 3.68

5.5 2.15 5.77

6.0

32.86 30.32 29.57 22.78

6.5 1.00

7.0

43.14

7.5

4.28

8.0

2.12

8.5

60.79

9.0 2.04

9.5

89.62

1H

2.17 2.39 1.04 2.05

2.02

Ph OH

146.32 145.83 140.82 140.72 129.17 129.11 128.67 128.16 126.61 124.96

166.56

7.859 7.854 7.842 7.837 7.371 7.368 7.363 7.350 7.348 7.287 7.282 7.269 7.256 7.253 7.249 7.197 7.194 7.191 7.176 7.097 7.093 7.081 7.076 4.340 4.322 4.304 4.286 2.619 2.593 2.396 2.384 2.376 2.351 2.336 2.330 2.315 2.262 2.243 2.223 2.205 2.164 2.102 1.598 1.522 1.515 1.502 1.496 1.483 1.481 1.357 1.339 1.321 1.300 1.282 0.895 0.877 0.858 0.000

a JF08-353H, AV400

CO2Et

Bu 4m

NMR, CDCl3, 400 MHz

0.5 ppm

b JF08-353C, AV400

CO2Et

Bu 4m

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

Ph OH

170

160 7.0

150 6.5

140 6.0

130 5.5

120 5.0

110 4.5

100

S115 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

1.0

30

Figure S58. Characterization of 4n. a 1H NMR spectrum. b 13C NMR spectrum.

20

13.94

7.5

3.39

8.0 2.20 2.50

8.5

32.70 30.32 29.50 22.78

9.0

42.98

9.5 2.23 2.48 0.97

1H

1.92

Ph OH

89.47

146.44 144.95 140.26 134.20 132.61 130.60 128.18 128.11 126.60 124.94

2.13 2.10 3.16 2.00

7.363 7.360 7.342 7.340 7.297 7.292 7.278 7.259 7.250 7.205 7.187 7.150 7.146 7.133 7.129 6.935 6.913 2.625 2.616 2.605 2.594 2.584 2.567 2.550 2.413 2.402 2.394 2.380 2.369 2.360 2.349 2.331 2.315 2.310 2.294 2.282 2.276 2.260 2.246 2.231 2.212 2.192 2.174 2.167 2.161 2.025 1.507 1.501 1.486 1.465 1.447 1.335 1.317 1.298 1.280 0.898 0.880 0.862

a JF08-327H, AV400

Cl

Bu

4n

NMR, CDCl3, 400 MHz

0.5 ppm

b JF08-327C, AV400

Cl

Bu

4n

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170

160

150

140

130

120

110 4.5

100

S116 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

1.0

30

Figure S59. Characterization of 4o. a 1H NMR spectrum. b 13C NMR spectrum.

20

13.99

5.0 3.41

5.5 2.19 2.34

6.0

32.69 30.39 29.58 22.83

6.5

42.70

7.0

4.55 1.02

7.5

2.08

8.0

54.93

8.5 3.11

9.0

89.47

9.5 1.01 1.02 1.00

1.98 2.17 1.03 1.03

1H

146.99 144.24 141.08 136.98 128.89 128.13 126.50 124.97 121.84 114.52 112.66

159.09

3.599 2.596 2.584 2.575 2.558 2.540 2.351 2.339 2.332 2.321 2.301 2.285 2.281 2.267 2.246 2.225 2.205 2.189 2.149 2.094 1.557 1.509 1.490 1.470 1.451 1.341 1.322 1.304

7.401 7.397 7.377 7.300 7.281 7.261 7.238 7.198 7.179 7.161 7.101 7.081 7.061 6.701 6.695 6.680 6.675 6.674 6.573 6.554 6.477 6.471 6.467

a JF08-351H, AV400

Ph OH

Bu OMe

4o NMR, CDCl3, 400 MHz

0.5 ppm

b JF08-351C, AV400

Ph OH

Bu OMe

4o

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170 7.5

160 7.0

150 6.5

140 6.0

130 5.5

120 5.0

110 4.5

100

S117 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

1.0

30

Figure S60. Characterization of 4p. a 1H NMR spectrum. b 13C NMR spectrum.

20

13.85

8.0 3.12

8.5 1.91 2.07

9.0

32.80 30.28 29.42 22.71

9.5 2.10 1.09 1.09 2.07 0.99

3.08 4.32 2.00

1H

43.01

146.17 145.68 140.29 136.61 132.39 130.64 130.30 129.98 129.66 128.25 128.19 126.69 126.27 126.23 126.19 126.15 125.46 124.91 123.45 123.41 123.37 122.75 89.53

7.403 7.384 7.367 7.363 7.359 7.345 7.344 7.299 7.294 7.281 7.262 7.253 7.245 7.210 7.207 7.204 7.194 7.189 7.171 7.152 7.132 2.660 2.649 2.638 2.626 2.605 2.589 2.474 2.463 2.441 2.429 2.421 2.409 2.357 2.342 2.336 2.321 2.308 2.302 2.229 2.210 2.197 2.190 2.179 2.021 1.541 1.527 1.521 1.507 1.486 1.468 1.342 1.323 1.305 1.286 0.894 0.875 0.857 -0.000

a JF08-329H, AV400

Ph OH

Bu CF3

4p

NMR, CDCl3, 400 MHz

0.5 ppm

b JF08-329C, AV400

Ph OH

Bu CF3

4p

NMR, CDCl3, 100 MHz

ppm

13C

200

Et

190

180

170

160

150

140

130

120

110

100

S118

90

80 3.0

70 2.5

60

2.0

50

1.5

40

1.0

30

Figure S61. Characterization of 4q. a 1H NMR spectrum. b 13C NMR spectrum.

20

12.78

3.5 3.14

4.0

23.06

4.5

32.86

5.0 2.08

5.5

43.27

6.0 1.07 2.14

6.5 1.06

7.0

55.59

7.5

3.09

8.0 0.97

8.5

88.96

9.0 3.00

9.5

138.72 132.65 128.07 127.43 125.86 125.56 125.49 120.86 110.75

1H

3.99

2.00

Et

148.40 147.14

156.34

7.356 7.353 7.333 7.251 7.186 7.168 7.148 7.123 7.117 7.107 7.101 7.097 7.086 7.079 7.060 7.042 6.829 6.816 6.811 6.794 6.776 6.764 6.743 4.302 3.725 2.848 2.829 2.807 2.788 2.770 2.575 2.566 2.554 2.546 2.534 2.525 2.513 2.504 2.404 2.396 2.385 2.376 2.371 2.363 2.352 2.343 2.326 2.307 2.289 2.274 2.255 2.134 2.115 2.096

a JF08-331H, AV400

Ph OH

OMe

4q

NMR, CDCl3, 400 MHz

0.5 ppm

b JF08-331C, AV400

Ph OH

OMe

4q

NMR, CDCl3, 100 MHz

ppm

Bu

13C

200

190

180

170 6.5

Ph OH

F

4r

NMR, CDCl3, 100 MHz

160

150

140 6.0

130 5.5

120 5.0

110 4.5

100

S119 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

1.0

30

Figure S62. Characterization of 4r. a 1H NMR spectrum. b 13C NMR spectrum.

20

13.89

7.0

3.24

7.5

2.09 2.35

8.0

32.86 29.80 29.76 22.63

JF08-352C, 8.5

43.17

9.0 1.09 1.04 1.08 2.05 2.00

9.5

89.53

2.06 2.29 2.07 2.89

1H

147.53 146.25 135.36 131.56 131.52 128.70 128.61 127.89 126.44 125.06 123.57 123.53 115.36 115.12

Bu

161.43 159.01

7.378 7.375 7.357 7.259 7.255 7.250 7.241 7.221 7.165 7.162 7.147 7.141 7.136 7.131 7.129 7.122 7.115 6.976 6.954 6.951 6.932 6.930 6.921 6.918 6.902 6.900 6.884 6.881 6.856 6.852 6.837 6.833 2.583 2.462 2.450 2.441 2.393 2.380 2.372 2.359 2.320 2.308 2.104 2.085 2.065 1.468 1.449 1.429 1.410 1.292 1.273 1.256 1.237 1.235 0.858 0.840 0.822 -0.000

a JF08-352H, AV400

Ph OH

F

4r

NMR, CDCl3, 400 MHz

0.5 ppm

b BBF02

ppm

13C

200

190

180

170

160

150

140

130

120 5.0

110 4.5

100

S120 4.0

90 3.5

80 3.0

70

2.5

60

2.0

50

1.5

40

30

Figure S63. Characterization of 4s. a 1H NMR spectrum. b 13C NMR spectrum. 14.18

5.5 3.42

6.0

25.21

6.5

32.88 32.39

7.0

1.03

7.5

42.71

8.0 6.28 2.03

8.5

60.51

9.0 2.00

9.5

89.32

2.06 2.47 4.03 1.98

1H

146.44 142.83 141.45 135.10 129.17 128.16 128.08 127.06 126.60 124.94

172.96

1.0 0.5

20

0.000

4.125 4.107 4.089 4.071 2.625 2.606 2.595 2.586 2.576 2.567 2.559 2.549 2.524 2.494 2.474 2.458 2.454 2.367 2.361 2.355 2.349 2.343 2.324 2.133 1.234 1.216 1.198

7.390 7.387 7.368 7.305 7.287 7.267 7.254 7.212 7.199 7.194 7.186 7.168 6.986 6.980 6.966 6.962

a JF08-354H, AV400

Ph OH Ph

4s CO2Et

NMR, CDCl3, 400 MHz

ppm

b JF08-354C, AV400

Ph OH Ph

4s CO2Et

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170

160 7.0

150 6.5

140 6.0

130 5.5

120 5.0

110 4.5

100

S121 4.0

90 3.5

80 3.0

70

2.5

60 2.0

50

1.5

40

30

Figure S64. Characterization of 4t. a 1H NMR spectrum. b 13C NMR spectrum. 11.68 5.90 5.44

7.5

4.03

8.0

28.46

8.5 1.01

9.0

42.60

9.5 4.14 1.00

1H

89.55

146.74 144.56 140.66 135.67 129.28 128.15 127.99 126.64 126.50 125.07

1.96 2.12 5.78

2.299 2.284 2.275 2.268 2.265 2.247 2.231 2.221 2.215 2.191 2.118 1.860 1.841 1.827 1.808 1.793 1.540 0.747 0.740 0.736 0.732 0.724

7.427 7.408 7.310 7.292 7.272 7.251 7.211 7.199 7.195 7.181 7.171 7.159 7.155 7.139

a JF08-334H, AV400

Ph OH Ph

4t

NMR, CDCl3, 400 MHz

1.0 0.5

20

ppm

b JF08-334C, AV400

Ph OH Ph

4t

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170

160

150

140

130

120 4

110

100

S122

90 3

80

70

2

60

50

40

30

Figure S65. Characterization of 4u. a 1H NMR spectrum. b 13C NMR spectrum.

20

14.01

5 3.00

6 2.31 2.08

7

33.19 30.28 30.04 22.97

8

42.47

9 4.16 2.11 1.08

1H

89.45

146.60 146.20 136.48 134.06 128.24 126.75 126.62 126.52 125.04 124.76

2.08 2.14 1.26 0.97 0.95 0.95

7.430 7.427 7.422 7.409 7.407 7.327 7.322 7.309 7.305 7.293 7.289 7.246 7.238 7.220 7.128 7.125 7.115 7.112 6.883 6.874 6.870 6.861 6.718 6.715 6.709 6.706 2.614 2.598 2.582 2.573 2.555 2.537 2.505 2.491 2.470 2.450 2.443 2.424 2.405 2.332 2.315 2.298 2.246 2.160 1.584 1.579 1.564 1.560 1.544 1.525 1.431 1.413 1.394 1.375 0.960 0.941 0.923 0.000

a JF08-335H BBFO1

Ph OH S

Bu

4u

NMR, CDCl3, 400 MHz

1 0 ppm

b JF08-335C BBFO1

Ph OH S

4u Bu

NMR, CDCl3, 100 MHz

ppm

Ph OH

13C

200

190

180

170

160

150 6.5

140 6.0

130 5.5

120 5.0

110 4.5

100

S123 4.0

90 3.5

80 3.0

70 2.5

60

2.0

50

1.5

40

1.0

30

Figure S66. Characterization of 4v. a 1H NMR spectrum. b 13C NMR spectrum.

20

14.12

7.0

3.04

7.5

2.19 6.03

8.0

33.25 31.76 29.41 29.38 28.25 22.65

8.5

43.72

9.0 1.12 3.14 3.07

9.5 0.97

1H

1.00

2.09 2.20 5.12 0.97

Ph OH

88.49

148.54 147.10 137.92 137.53 129.79 128.42 128.20 127.12 126.45 126.08 125.08 124.83 120.13

2.551 2.482 2.456 2.436 2.415 2.395 2.377 2.253 2.247 2.236 2.219 1.570 1.559 1.399 1.384 1.365 1.355 1.349 1.341 0.930 0.922 0.912

7.445 7.441 7.423 7.422 7.331 7.312 7.292 7.237 7.222 7.216 7.212 7.203 7.191 7.186 7.138 7.126 6.838 6.797 6.328 6.287

a JF08-350H, AV400

Ph

n-C6H13

4v

NMR, CDCl3, 400 MHz

0.5 ppm

b JF08-350C, AV400

Ph

n-C6H13

4v

NMR, CDCl3, 100 MHz

ppm

13C

200

190

180

170 7.5

160 7.0

150 6.5

140 6.0

130 5.5

120 5.0

110 4.5

100

S124 4.0

90 3.5

80 3.0

70

2.5

60 2.0

50

40 33.76

8.0

42.27

8.5 1.00

9.0 2.06

9.5 1.06 1.06

2.00 2.08 6.18 2.91 1.97

1H

89.79

146.45 142.51 140.76 136.92 135.60 129.58 128.39 128.33 128.24 128.11 127.42 127.15 126.80 125.00

0.000

3.094 3.079 3.063 3.052 3.037 3.022 2.962 2.943 2.924 2.901 2.882 2.510 2.494 2.476 2.214

7.489 7.486 7.468 7.342 7.338 7.324 7.304 7.248 7.246 7.240 7.236 7.229 7.224 7.213 7.204 7.198 7.190 7.185 7.135 7.131 7.121 7.119 7.113 7.103 7.094 7.089 6.955 6.951 6.936 6.931

a JF08-355H, AV400

Ph OH Ph

Ph

4w

NMR, CDCl3, 400 MHz

1.5 1.0

30

Figure S67. Characterization of 4w. a 1H NMR spectrum. b 13C NMR spectrum. 0.5

20 ppm

b JF08-355C, AV400

Ph OH Ph

Ph

4w

NMR, CDCl3, 100 MHz

ppm

a

PivO

N Bu Bu

Me 5a

1H

NMR, CDCl3, 400 MHz

b

PivO

N Bu Bu

Me 5a 13C

NMR, CDCl3, 100 MHz

Figure S68. Characterization of 5a. a 1H NMR spectrum. b 13C NMR spectrum. S125

a

PivO

N Bu Bu

MeO 5b 1H

NMR, CDCl3, 400 MHz

b

PivO

N Bu Bu

MeO 5b 13C

NMR, CDCl3, 100 MHz

Figure S69. Characterization of 5b. a 1H NMR spectrum. b 13C NMR spectrum. S126

a

PivO

N Bu Bu 5c

1H

NMR, CDCl3, 400 MHz

b

PivO

N Bu Bu 5c

13C

NMR, CDCl3, 100 MHz

Figure S70. Characterization of 5c. a 1H NMR spectrum. b 13C NMR spectrum. S127

a

Me

N

Bu Pr

6a 1H

NMR, CDCl3, 400 MHz

b

Me

N

Bu Pr

6a

13C

NMR, CDCl3, 100 MHz

Figure S71. Characterization of 6a. a 1H NMR spectrum. b 13C NMR spectrum. S128

a

MeO

N

Bu Pr

6b 1H

NMR, CDCl3, 400 MHz

b

MeO

N

Bu Pr

6b

13C

NMR, CDCl3, 100 MHz

Figure S72. Characterization of 6b. a 1H NMR spectrum. b 13C NMR spectrum. S129

a

N

Bu Pr

6c 1H

NMR, CDCl3, 400 MHz

b

N

Bu Pr

6c 13C

NMR, CDCl3, 100 MHz

Figure S73. Characterization of 6c. a 1H NMR spectrum. b 13C NMR spectrum. S130

a

-0.001

2.505 2.500 2.496

3.316

7.598 7.581 7.577 7.452 7.449 7.433 7.428 7.417 7.401 7.398 7.395 7.384 7.382 7.370 7.351 7.333 7.277 7.269 7.257 7.238 6.434

JF09-123H AV400

Ph Ph Cl

Ph Rh Cl 2

8 NMR, DMSO-d6, 400 MHz

9.0

8.5

8.0

7.5

7.0

2.00 9.04 4.08

9.5

6.5

6.0

5.5

5.0

4.5

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

ppm

2.00

1H

b

Cl

140

100

82.01 81.92

99.05 98.99

Ph Ph

131.70 131.09 130.37 129.97 129.64 128.78 128.74 128.42 110.95 110.89

JF09-123C BBFO2

Ph Rh Cl 2

8 13C

NMR, DMSO-d6, 100 MHz

200

190

180

170

160

150

130

120

110

90

80

70

60

50

40

30

Figure S74. Characterization of 8. a 1H NMR spectrum. b 13C NMR spectrum. S131

20

ppm