Metal Catalyzed Carbonylation: Catalyzed Carbonylation: Metal ...

Metal-Catalyzed Carbonylation: MetalFrom the Industry to the Bench

Tom Hsieh Dong Research Group Organic and Biological Seminar Series Department of Chemistry, University of Toronto November 9, 2009

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Outline Introduction to carbon monoxide (CO) Preparation of CO Uses of CO in some industrial processes Properties of the CO molecule Reductive carbonylation of nitro compounds: use of CO as a stoichiometric redundant in the p preparation p of N-heterocycles Carbonylative cross-coupling of organic h lid halides: use off CO as a C1 source in the preparation of carboxylic acid derivatives

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Preparation of Carbon Monoxide Burning elemental carbon in restricted supply of oxygen gas

Reduction of carbon dioxide with coke

Dehydration of formic acid (small scale for laboratory)

Water-gas shift reaction (preparation of synthesis gas)

Housecroft and Sharpe. Inorganic Chemisty. Prentice Hall: England 2001.

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Industrial Process: FischerFischer-Tropsch Synthesis

Discovered in 1922 Commercialized in 1928 Heterogeneous catalysis Fe and Co catalysts 200-300 oC and 10-60 bar Highly Hi hl exothermic th i 6.5 Mt / yr by 1944 Used as synthetic lubricants and synthetic diesel/jet fuels

Prof. Franz Fischer

Dr. Hans Tropsch


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Proposed FischerFischer-Tropsch Mechanism


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Industrial Process: Hydroformylation

Discovered and commercialized in 1938 by Otto Roelen at Ruhrchemie (Germany) Important industrial homogeneous catalysis Combined 7.2 Mt / yr 50% of world capacity located in Europe and 30% in USA Propene important olefin starting material First Fi t active ti catalyst: t l t [HCo(CO) [HC (CO)3] Hagen. Industrial Catalysis. Wiley-VCH: Weinheim 2006.

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Industrial Process: Hydroformylation

Ca a ys s Catalysts Co

Co/phosphine

Rh/phosphine

Reaction Pressure ((bar))

200-300

50-100

7-25

Reaction Temperature (°C)

140-180

180-200

90-125

4:1

9:1

19:1

Catalyst

[HCo(CO)4]

[HCo(CO)3(PBu3)]

[HRh(CO)(PPh3)3] / PPh3 up to 1:500

Main Products

aldehydes

alcohols

aldehydes

1

15

0.9

L:B of aldehyde

Hydrogenation to alkanes (%)

Hagen. Industrial Catalysis. Wiley-VCH: Weinheim 2006.

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Hydroformylation: Catalytic Cycle

β-H elimination

Migratory Insertion

β-H elimination

Coordination

Hydrorhodation

Migratory Insertion

Hydrorhodation


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Use of [Rh] in Hydroformylation Advantages of using [Rh] over [Co] [Rh] is 1000x more active Excess of PPh3 allows high linear aldehyde selectivity Use of PPh3 increases catalyst stability and prolongs its life [Rh] has low volatility so purification of product is simpler

[Rh] process is high g cost: work up, catalyst y recycling y g and corrosion Intensive research in developing heterogeneous [Rh] catalyst Two-phase technology: uses water-soluble [Rh] with TPPTS Improved L:B selectivity (> 19:1) Ease of [Rh] catalyst separation and recycling


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Industrial Processes: Production of Acetic Acid

Commercialized in 1970 by Monsanto Important industrial catalytic process Combined 3.5 Mt / yr 60% of world’s acetyls One of few industrial catalytic processes whose kinetics are fully known Active catalyst: [RhI2(CO)2]¯


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The Monsanto Process: Catalytic Cycle

Oxidative Addition

Reductive Elimination


Migratory Insertion

Ligand Exchange

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The Monsanto Process

Process is licensed worldwide Mild reaction conditions: 30-40 bar and 150-200 °C Numerous columns needed for product isolation Stainless steel needed for all plant components due to corrosiveness of iodide In 1996 1996, the Cativa Process introduced by BP Chemicals Higher reactivity about 3x Up to 0.5 Mt / yr via this modification


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Carbon Monoxide

“carbene-like”

“dinitrogen-like”

Colorless and odorless gas Highly flammable and toxic Bond length: 112.8 pm Bond energy: 257 kcal/mol Dipole Di l moment: 0 0.112 112 D Insoluble in water (26 mg/L) HOMO is lone pair on C ((σ3) 13

Carbon Monoxide C≡O

N≡N

HC≡CH

O=O

O=C=O

Me2C=O

Bond Energy (kcal/mol)

257

226

200

119

193

193

Bond Length (pm)

112.8

109.7

120.3

121.0

116.0

121.3

Dipole Moment (D)

0.112

0

0

0

0

2.91

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Use of Carbon Monoxide in Synthesis

CO + Substrate

Metal-Catalyzed Carbonylation

Aldehydes

Acyl halides

Aldoximes

Nitriles

Ketones

Anhydrides

Ketenes

Carbonates

Ketoximes

Carbamates

Esters

Isocyanates

Lactones

Ureas

Carboxylic acids

Amines

A id Amides

A compounds Azo d

Lactams

Heterocycles

, ca bo y s 1,2-Dicarbonyls

Carbocycles Ca bocyc es

1,4-Dicarbonyls

Metal complexes 15

Reductive Carbonylation of Nitro Compounds

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Reductive Carbonylation

The use of CO for the reduction of chemical bonds while forming CO2, for example:

NO2 reduced to nitroso and/or nitrene CO oxidized to CO2 – a stoichiometric reductant

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First Example of Reductive Carbonylation In 1949, Buckley and Ray reported the first reductive carbonylation

Trace amounts of reduction occurred at 200 oC or < 2500 atm Nickel and cobalt catalysts had no effect

Buckley and Ray. J. Chem. Soc. 1949, 1154.

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Towards Catalysis In 1965, Kmiecik identified Fe(CO)5 as a efficient catalyst for the reductive carbonylation of nitrobenzene

K Kmiecik i ik iisolated l t d azoxybenzene b as a possible intermediate

Kmiecik. J. Org. Chem. 1965, 30, 2014.

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Synthesis of Isocyanates In 1967, Hardy and Bennett reported the first reduction of nitro aromatics to generate isocyanates catalytically

R = EDG and EWG Solvents: nonpolar Catalysts: Pd, Rh/Al, Rh/C Lewis acids: FeX3, AlX3, SnCl4, CuCl2

Hardy and Bennett. Tetrahedron Lett. 1967, 11, 961.

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Advancements in Reductive Carbonylation Since this discovery, research in this area of reductive carbonylation has greatly increased Big push for the formation of other targets including isocyanates, carbamates, b t ureas, and d amines i

Chem. Rev. 1996, 96, 2035. and Curr. Org. Chem. 2006, 10, 1479.

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Isocyanates from Phosgenation

> 2 Mt produced per year TDI and MDI account for > 95% of the world’s diisocyanates made Important precursors to numerous polyurethanes Phosgene is highly toxic L Large amounts t off corrosive i HCl produced d d The Polyurethanes Book; Wiley: New York, NY, 2003. and Dalton Trans. 2009, 6251.

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Reductive Carbonylation Mechanism

Chem. Rev. 1996, 96, 2035.

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Diversity of Nitroarenes in Reductive Carbonylation

Catalytic Reductive Carbonylation of Organic Nitro Compounds. Kluwer Academic Publishers: Netherlands, 1997.

Benzimidazoles via [Ru] Catalysis

Entry

Solvent

T (oC)

%A

%B

%C

1

Benzene

220

86

4

---

2

Benzene

170

34

trace

47

3 (no [Ru])

Benzene

220

---

---

85

4

CH3CN

170

82

---

4

Limited number of stable imines C also Can l b be d done with ith th the iimine i made d in i situ it Cenini and coworkers. J. Mol. Catal. 1992, 72, 283.

Benzimidazoles via [Pd] Catalysis

E t Entry

R

Ti Time (h)

T (oC)

PCO (atm) ( t )

%A

%B

1

Ph

5

180

40

83

trace

2

Ph

5

180

20

81

---

3

Ph

5

160

40

78

11

4

Ph

5

140

40

55

10

5

p-ClC6H4

2

180

40

55

45

6

p-OMeC6H4

3

180

40

80

10

2,4,6-Trimethylbenzoic acid (TMBH) is required or else no reaction Cenini and coworkers. J. Mol. Catal. 1994, 59, 3375.

Carbazoles via [Pd] Catalysis

Previous forcing conditions: Ru3(CO)12, 50 atm CO, CO 220 oC Low Catalyst loading: 0.5 mol % Pd, 3.5 mol % phen, 97% yield Smitrovich and Davies. Org. Lett. 2004, 6, 533.

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Merck’s Kinase Inhibitors

quantitative yield Pd(TFA)2 (0.1 (0 1 mol %) TMphen (1.0 mol %) CO (1 atm) DMF, 70 oC

Conditions: Pd(OAc)2 (6 mol %) %), PPh3 (24 mol %) %), CO (4 atm) Difficult purification required development of new reaction conditions Davies and coworkers. Tetrahedron. 2005, 61, 6425.

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Substrate Scope of Merck’s Conditions

Varying Conditions Pd(OAc)2 or Pd(TFA)2 0.1 – 1.5 mol% phen or TMphen 0.7 – 3 mol % CO ((1 – 2 atm)) 70 – 80 oC Davies and coworkers. Tetrahedron. 2005, 61, 6425.

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Proposed Mechanism for Indole Formation

Davies and coworkers. Tetrahedron. 2005, 61, 6425.

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Nitroalkenes in Reductive Carbonylation Proposal: extension to Nitroalkenes Interested I t t d in i accessing i various i Nh t N-heterocycles l

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Synthesis of Nitroalkenes Preparation of the model nitroalkene substrate

Preparation of symmetrical arylnitroalkenes

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Substrate Scope

a

Isolated yield.

b

Regioselectivity (based on 1H NMR integrations) is 47:53.

Electron-rich substrates are tolerated 33

Substrate Scope

a

Isolated yield.

c

Regioselectivity is 42:58.

d

Regioselectivity is 51:49.

Electron-poor substrates are tolerated 34

Regioselective C– C–H Bond Amination

Structure solved by Dr. Alan Lough

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Indoles via Reduction of Nitroalkenes with CO

Tolerant of both electron-rich and electron-poor substrates – 10 examples, 58–98% Versatile methodology for making indoles Fe, Fe Rh Rh, Pt and Pd catalysts Bidentate N- and P-based ligands

New strategy for the synthesis of nitroalkenes Hsieh and Dong. Tetrahedron. 2009, 65, 3062 (Invited Article).

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Carbonylative cross cross--coupling of organic halides

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Biologically Active Compounds via Carbonylation

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Seeberger and coworkers. Org. Lett. 2002, 4, 2965.

Kogen and coworkers. Tetrahedron. 2005, 61, 2075.

39


Desmaele and coworkers. Tetrahedron Lett. 2005, 46, 2201.

Song and coworkers. J. Org. Chem. 2001, 66, 605.

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Carbonylation of Aryl Halides

T i lC Typical Conditions diti

X = Cl, Br, I, OTf, OMs and OTs

[Pd] = Pd(0) and Pd(II)

L = mono- and bidentate phosphines

Base = organic and inorganic

T = 100 to 180 °C

PCO = 1 to 40 bar Organometallics. 2008, 27, 5402. and Angew. Chem. Int. Ed. 2009, 48, 4114.

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Profen Drugs: Chiral Carboxylic Acids

Sub-class of the non-steroidal anti-inflammatory drugs (NSAIDs) Compared to aryl-X, small amounts of research done with 2° alkyl-X. Lack of efficient methods of preparing profens enantioselectively 42

State of the Art: Asymmetric Profen Preparation Hydrocarboxylation and Hydroesterification

Primarily palladium catalysis Typical enantioselectivities < 60% ee Regioselectivity g yp problem – linear and branched p products Difficult to obtain high levels of both regio- and enantioselectivity

Dalton Trans. 2008, 853. and Top Organomet. Chem. 2006, 18, 97.

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Stoichiometric Alkoxycarbonylation

90% inversion of stereochemistry

Stille and coworkers. J. Am. Chem. Soc. 1974, 96, 4983.

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Stereoconvergent Catalytic Hydroxycarbonylation

Mild conditions: rt, 4-12 h, CO (1 atm) 9 different ligands were tested Low L conversion i and d ee

No substrate scope

Arzoumanian and coworkers. Organometallics 1988, 7, 59.

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Stereospecific Catalytic Hydroxycarbonylation

Poor Regioselectivity Significant amount of homobenzyl acid, vinylarene and alkylarene byproducts High enantioselectivity at low conversions Best result: 36% yield, 91% ee

High pressure of CO (43 atm) Sparacino and coworkers. J. Org. Chem. 1991, 56, 1928.

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Alkoxycarbonylation of 2° 2° Alkyl Halides Proposal

Two possibilities for asymmetric induction Stereoconvergent: a chiral catalyst facilitates the transformation of racemic substrates to enantioenriched products Stereospecific: an achiral catalyst facilitates the transformation of enantioenriched substrates to enantioenriched products with either retention or inversion of stereochemistry Charles Yeung

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Pd--Catalyzed Enantioselective Alkoxycarbonylation Pd New catalytic transformation

Pd(0) and Pd(II) successfully catalyze this transformation Ni, Rh, Ru, Pt and Fe are ineffective catalysts

Conventional bidentate ligands are ineffective e.g. BINAP, BIPHEP, SEGPHOS and DUPHOS

Initial hit with Pd(OAc)2, Et3N, CH2Cl2, MeOH P(2-furyl) P(2 f r l)3 – 46% GC yield ield (R)-Monophos – 48% GC yield, 33% ee

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Carbonylation of Benzylic Bromides R = R' = Ph

MeOH, 67%, 21% ee

R = Ar, R' = Ar'

MeOH, 20%, 49% ee i-PrOH, 12%, 72% ee

Ar =

Ar' =

High yields with low ee and vice versa Reactions with i-PrOH generally give higher ee than with MeOH Product distribution differ between MeOH and i-PrOH Substitution is the major competing pathway with MeOH β-H elimination is the major competing pathway with i-PrOH 49

Summary and Conclusion Carbon monoxide is used throughout synthetic chemistry Industrial p processes ((Mt scale)) and academic research ((mg g scale))

Major advancements in reductive carbonylation

1949 – no catalysis, y , 250 °C,, and 3000 atm of CO 2009 – numerous catalysts (0.1 mol %), 70 °C and 1 atm of CO Significant improvements – possible industrial applications soon Beyond nitroarenes

Carbonylative cross-coupling of many R-X electrophiles

Aryl, vinyl, benzyl and alkyl Halides, sulfonates, acetates, carbonates, etc. Directed carbonylation of sp2 C–H is also known p Enantioselective variants are in development 50

Acknowledgements

Prof. Vy M. Dong Charles Yeung Dong Research Group 51