Michael J KrischeProfessor
Department of Chemistry
The Robert A. Welch Chair in Sciencemkrische@cm.utexas.edu
The University of Texas at Austin
Department of Chemistry, College of Natural Sciences
105 East 24th Street
Austin, TX 78712
B.S., University of California Berkley (1989)
Fulbright Fellowship, Helsinki University (1990)
Ph.D., Stanford University (1996)
Postdoctoral Studies, Universite' Louis Pasteur (1999)
Transition Metal Catalysis, Natural Product Synthesis, Organometallic And Green Chemistry
Carbon-carbon bond formation lies at the heart of chemical synthesis. The largest volume application of homogenous metal catalyzed C-C coupling is alkene hydroformylation, which may be viewed as the prototypical C-C bond forming hydrogenation. Our laboratory is engaged in the first systematic efforts to develop C-C bond forming hydrogenations beyond hydroformylation - processes wherein two or more reactants are hydrogenated to form a single, more complex product. Using cationic rhodium and iridium catalysts, we have found that diverse π-unsaturated reactants reductively couple to carbonyl compounds and imines under hydrogenation conditions, offering a byproduct-free alternative to stoichiometric organometallics in a range of classical C=X (X = O, NR) addition processes. This concept is extended further via “C-C bond forming transfer hydrogenation”. In such processes, the exchange of hydrogen between alcohols and unsaturated reactants serves to generate aldehyde-organometal pairs that combine to give products of carbonyl addition or hydrohydroxyalkylation. Direct alcohol CH-functionalization in this manner is again byproduct-free, and avoids discrete redox manipulations often required to convert alcohols to aldehydes. Using these merged redox-C-C bond construction events, total syntheses of 6-deoxyerythronolide B, bryostatin 7, cyanolide A and roxaticin, and formal syntheses of rifamycin S and scytophycin C, were accomplished. These syntheses are the most concise routes reported, to date, to any member of these natural products families. More broadly, this body of work evokes question of whether all processes that now rely upon premetallated reagents can be conducted catalytically under hydrogenation or transfer hydrogenation conditions in the absence of stoichiometric organometallics.
Liang, T.; Zhang, W.; Krische M. J. “Iridium Catalyzed C-C Coupling of a Simple Propargyl Ether with Primary Alcohols: Enantioselective Homoaldol Addition via Redox-Triggered (Z)-Siloxyallylation,” J. Am. Chem. Soc. 137 (2015): 16024.
Kasun, Z. A.; Gao, X.; Lipinski, R. M.; Krische, M. J.“Direct Generation of Triketide Stereopolyads via Merged Redox-Construction Events: Total Synthesis of (+)-Zincophorin Methyl Ester,” J. Am. Chem. Soc. 137 (2015): 8900.
Gao, X.; Woo, S. K.; Krische, M. J. “Total Synthesis of 6-Deoxyerythronolide B via C-C Bond-Forming Transfer Hydrogenation,” J. Am. Chem. Soc. 135 (2013): 4223.
Dechert-Schmitt, A.-M. R.; Schmitt, D. C.; Krische, M. J. “Site-Selective Primary Alcohol Dehydrogenation Enables Protecting Group-Free Diastereoselective C-C Coupling of 1,3-Glycols and Allyl Acetate,” Angew. Chem. Int. Ed. 52 (2013): 3195.
Zbieg, J. R.; Yamaguchi, E.; McInturff, E. L.; Krische, M. J. “Enantioselective C-H Crotylation of Primary Alcohols via Hydrohydroxyalkylation of Butadiene,” Science 336 (2012): 324.
Lu, Y.; Woo, S. K.; Krische, M. J. “Total Synthesis of Bryostatin 7 via C-C Bond Forming Hydrogenation,” J. Am. Chem. Soc. 132 (2011): 13876.
- Royal Society of Chemistry, Pedlar Award, 2015
- Eun Lee Lectureship, Korea, 2015
- JSPS Fellow, 2013
- ACS Cope Scholar Award, 2013
- Fellow of the Royal Society of Chemistry, 2013
- GlaxoSmithKline Scholar Award, 2011
- Mukaiyama Award, 2010
- Humboldt Research Award, 2009
- Tetrahedron Young Investigator Award, 2009
- Novartis Lectureship Award, 2008
- Presidential Green Chemistry Award, 2007
- Dowpharma Prize, 2007
- Elias J. Corey Award, 2007
- Solvias Ligand Prize, 2006
- Johnson & Johnson Focused Giving Award, 2005
- Japanese Society of Synthetic Chemistry, Lectureship on Organic Synthesis, 2005
- Camille Dreyfus Teacher Scholar Award, 2003
- Alfred P. Sloan Research Fellowship, 2003
- Cottrell Scholar Award, 2002
- Lilly Grantee Award, 2002
- Frasch Foundation Award in Chemistry, 2002
- National Science Foundation-CAREER Award, 2000
- NIH Post-Doctoral Fellow, 1997
- Peter Veatch Fellow, 1995
- Sigma Xi Fellow, 1990
- Fulbright Fellow, 1990
- Presidents Undergraduate Fellow, 1989