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.
S5
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.;
S66
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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
