Catalytic C-C Bond Formation via Capture of Hydrogenation Intermediates

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Michael J. Krische

Presented byLouis-Philippe BeaulieuUniversité de Montréal

April 7th 2009

Catalytic C-C Bond Formation via Capture of Hydrogenation Intermediates

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Michael J. Krische: Biographical Information

Obtained a B.S. degree in chemistry from the University of California at Berkeley under the supervision of Professor Henry Rapoport. He received his Ph.D. in 1996 under the mentorship of Professor Barry Trost and he studied with Jean-Marie Lehn at the Université Louis Pasteur as a post-doctoral fellow.

In 1999, he was appointed Assistant Professor at the University of Texas at Austin. He was Promoted to Full Professor in 2004, and was awarded the Robert A. Welch Chair in 2007.

Selected awards include the Tetrahedron Young Investor Award (2009), Novartis Lectureship Award (2008), Elias J. Corey Award (2007) and Dreyfus Teacher Scholar Award (2003).

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Formation of C-C Bonds via Catalytic Hydrogenation and Transfer Hydrogenation: General concept

Conventional reduction

C-C bondformation

Homolytic activation of H2 to form a high-valent dihydride

Heterolytic activation of H2 to form a low-valent monohydride

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Formation of C-C Bonds via Catalytic Hydrogenation and Transfer Hydrogenation: General concept

Ngai, M. Y.; Kong, J. R.; Krische, M. J. J. Org. Chem. 2007, 72, 1063-1072.Skucas, E.; Kong, J. R.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 7242-7243.

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Tenets of Green Chemistry

Li, C. J.; Trost, B. M. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 13197-13202.Baran, P. S.; Maimone, T. J.; Richter, J. M. Nature (2007, 446, 404-408.

• Atom economy: Reaction yield = x 100% Quantity of product isolatedTheoretical quantity of product

Atom economy= x 100% MW of desired productMW of all products

• Synthesis without protections

• Development of tandem and cascade reactions

• Use of environmentally bening solvents

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Historical and Industrial Perspective of Catalytic Hydrogenation

Milestones in catalytic hydrogenataion

1500s Paracelsus (1493–1541) and Robert Boyle (1671)

1783 Antoine Lavoisier

1897 Paul Sabatier

1905 Fritz Haber and Carl Bosch

1923 Franz J.E. Fischer and Hans Tropsch

1938 Otto Roelen

1964 Geoffrey Wilkinson

1968-1980

William S. Knowles, Henri B. Kagan, Ryoji Noyori6

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Hydrogen-Mediated Reductive Aldol Coupling

Catalyst Ligand Additive (mol %)

Yield aldol (syn/anti)

Yield 1,4-reduction

Rh(PPh3)3Cl - - 1 % (99:1) 95%

Rh(COD)2OTf

Ph3P - 21% (99:1) 25%

Rh(COD)2OTf

Ph3P KOAc (30) 59% (58:1) 21%

Rh(COD)2OTf

(p-F3CC6H4)3P

- 57% (14:1) 22%

Rh(COD)2OTf

(p-F3CC6H4)3P

KOAc (30) 89% (10:1) 0.1%

Jang, H. Y.; Huddleston, R. R.; Krische, M. J. J. Am. Chem. Soc. 2002, 124, 15156-15157.

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Stereochemical model

(Z)-enolate, Zimmerman-Traxler-type transition state

Stereospecific Z(O)-enolate formation

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Hydrogen-Mediated Reductive Aldol Coupling

Schrock, R. R.; Osborn, J. A. J. Am. Chem. Soc. 1976, 98, 2134-2143.

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Hydrogen-Mediated Reductive Aldol Coupling

Entry Ligand [DCM], M Yield (%) dr

1 Ph3P

0.1

31 3:1

2 Ph3As 17 7:1

3 (2-Fur)Ph2P 24 6:1

4 (2-Fur)

2PhP52 15:1

5 (2-Fur) 3P 74 19:1

6a (2-Fur) 3P 0.3 91 16:1a 10 mol% of Li2CO3

Jung, C. K.; Garner, S. A.; Krische, M. J. Org. Lett. 2006, 8, 519-522.

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Hydrogen-Mediated Reductive Aldol Coupling

Jung, C. K.; Garner, S. A.; Krische, M. J. Org. Lett. 2006, 8, 519-522.Ngai, M. Y.; Kong, J. R.; Krische, M. J. J. Org. Chem. 2007, 72, 1063-1072.

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Hydrogen-Mediated Reductive Aldol Coupling: Enantioselective Version

Front view of [Rh(cod)(L)2]OTfomitting the methyl groups, triflate ion, and COD

Entry R1 R2 Yield (%)

syn:anti ee (syn)

1 Me BnO 85 25:1 91

2 Me PhtN 88 50:1 96

3 Me 1-Me-indol-3-yl

92 15:1 86

4 Me Ph 70 25:1 89

5 Et BnO 96 21:1 88

6 Et PhtN 94 45:1 95

7 Et 1-Me-indol-3-yl

97 25:1 90

8 Et Ph 76 22:1 90Bee, C.; Soo, B. H.; Hassan, A.; Iida, H.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 2746-2747.

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Hydrogen-Mediated Reductive Aldol Coupling

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Ngai, M. Y.; Kong, J. R.; Krische, M. J. J. Org. Chem. 2007, 72, 1063-1072.

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Huddleston, R. R.; Krische, M. J. Org. Lett. 2003, 5, 1143-1146.

Hydrogen-Mediated Reductive Aldol Coupling

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Marriner, G. A.; Garner, S. A.; Jang, H. Y.; Krische, M. J. J. Org. Chem. 2004, 69, 1380-1382.

Hydrogen-Mediated Reductive Aldol Coupling

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Hydrogen-Mediated Conjugated Alkyne-Carbonyl Coupling

Komanduri, V.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16448-16449.15

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Hydrogen-Mediated Conjugated Alkyne-Carbonyl Coupling

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Jang, H. Y.; Krische, M. J. Acc. Chem. Res. 2004, 37, 653-661.

Dewar-Chatt-Duncanson Model

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Komanduri, V.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16448-16449.

Hydrogen-Mediated Conjugated Alkyne-Carbonyl Coupling

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Komanduri, V.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16448-16449.Iida, H.; Krische, M. J. Top. Curr. Chem. 2007; 279, 77-104.

Hydrogen-Mediated Conjugated Alkyne-Carbonyl Coupling

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Kong, J. R.; Cho, C. W.; Krische, M. J. J. Am. Chem. Soc. 2005, 127, 11269-11276.

Hydrogen-Mediated Conjugated Alkyne-Ethyl (N-Sulfinyl)iminoacetates Coupling

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Kong, J. R.; Cho, C. W.; Krische, M. J. J. Am. Chem. Soc. 2005, 127, 11269-11276.20

Hydrogen-Mediated Conjugated Alkyne-Ethyl (N-Sulfinyl)iminoacetates Coupling

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Huddleston, R. R.; Jang, H. Y.; Krische, M. J. J. Am. Chem. Soc. 2003, 125, 11488-11489.

Hydrogen-Mediated Conjugated Alkyne-Carbonyl Coupling

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Hydrogen-Mediated Conjugated Alkyne-Carbonyl Coupling

Jang, H. Y.; Krische, M. J. Acc. Chem. Res. 2004, 37, 653-661.

Competition experiments reveal coupling to the strongest π-acid

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Jang, H. Y.; Hughes, F. W.; Gong, H.; Zhang, J.; Brodbelt, J. S.; Krische, M. J. J. Am. Chem. Soc. 2005, 127, 6174-6175.

Reductive Cyclization of 1,6-Enynesvia Rhodium-Catalyzed Asymmetric Hydrogenation:C−C Bond Formation Precedes Hydrogen Activation

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Reductive Cyclization of 1,6-Enynesvia Rhodium-Catalyzed Asymmetric Hydrogenation:C−C Bond Formation Precedes Hydrogen Activation

Jang, H. Y.; Hughes, F. W.; Gong, H.; Zhang, J.; Brodbelt, J. S.; Krische, M. J. J. Am. Chem. Soc. 2005, 127, 6174-6175.2

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Jang, H. Y.; Hughes, F. W.; Gong, H.; Zhang, J.; Brodbelt, J. S.; Krische, M. J. J. Am. Chem. Soc. 2005, 127, 6174-6175.

Reductive Cyclization of 1,6-Enynesvia Rhodium-Catalyzed Asymmetric Hydrogenation:C−C Bond Formation Precedes Hydrogen Activation

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Reductive Cyclization of Acetylenic Aldehydes

Rhee, J. U.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 10674-10675.26

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Carbonyl and Imine Z-Dienylation via Multicomponent ReductiveCoupling of Acetylene to Aldehydes and α-Ketoesters

Kong, J. R.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16040-16041. Iida, H.; Krische, M. J. Top. Curr. Chem. 2007; 279, 77-104.2

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Carbonyl and Imine Z-Dienylation via Multicomponent ReductiveCoupling of Acetylene to Aldehydes and N-Arylsulfonyl Imines

Kong, J. R.; Krische, M. J. J. Am. Chem. Soc. 2006, 128, 16040-16041.Skucas, E.; Kong, J. R.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 7242-7243.2

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Reductive Coupling of Disubstituted Alkynes to Activated Ketones

π-Backbonding in the metal-alkyne complex, as described by the Dewar-Chatt-Duncanson model, may facilitate alkyne-C=X (X = O, NR) oxidative coupling by conferring nucleophilic character to the bound alkyne.

Due to relativistic effects, iridium is a stronger π-donor than rhodium: (Ph3P)2M(Cl)(CO), M = Ir, νco = 1965 cm-1; M = Rh, νco = 1980 cm-1.

This may account for the ability of iridium-based catalysts to activate nonconjugated alkynes, which embody higher lying LUMOs.

Ngai, M. Y.; Barchuk, A.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 280-281..Vaska, L.; Peone, J. Chem. Commun. 1971, 419.2

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Reductive Coupling of Disubstituted Alkynes to Activated Ketones

Ngai, M. Y.; Barchuk, A.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 280-281..30

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Reductive Coupling of Disubstituted Alkynes to N-Arylsulfonyl Imines

Ngai, M. Y.; Barchuk, A.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 12644-12645.

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Reverse Prenylation via Iridium-Catalyzed Hydrogenative Coupling of Dimethylallene

Skucas, E.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 12678-12679.

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Reverse Prenylation via Iridium-Catalyzed Hydrogen Autotransfer and Transfer Hydrogenation

Bower, J. F.; Skucas, E.; Patman, R. L.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 15134-15135.33

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Reverse Prenylation via Iridium-Catalyzed Hydrogen Autotransfer and Transfer Hydrogenation

Bower, J. F.; Skucas, E.; Patman, R. L.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 15134-15135.

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A rapid redox equilibration in advance of C-C coupling is operative

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Ruthenium-Catalyzed C-C Bond-Forming TransferHydrogenation

Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 6338-6339.Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14120-14122.3

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Ruthenium-Catalyzed C-C Bond-Forming TransferHydrogenation

Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 6338-6339.Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14120-14122.

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Enantioselective Iridium-Catalyzed Carbonyl Allylation

Kim, I. S.; Ngai, M. Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14891-14899.

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Enantioselective Iridium-Catalyzed Carbonyl Allylation

Kim, I. S.; Ngai, M. Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14891-14899.

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Enantioselective Iridium-Catalyzed Carbonyl Allylation

Kim, I. S.; Ngai, M. Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14891-14899.

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Enantioselective Iridium-Catalyzed Carbonyl Allylation

Kim, I. S.; Ngai, M. Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14891-14899.

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Conclusion

• The work of M. J. Krische is the first systematic investigation of the use of catalytic hydrogenation as a method of C-C coupling since the advent of alkene hydroformylation and the Fischer-Tropsch reaction.

•C-C Bond-forming hydrogenation reactions are analogous to conventional carabanion chemistry, yet they feature complete atom-economy . This makes them particularly suitable candidate reactions for industrial-scale applications .

• Several other retrosynthetic disconnections remain to be explored and may lead to other interesting reactions.

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