Synthetic Methods & Natural Product Synthesis at the University of Texas at Austin

Principal Investigator: 

Professor Michael J. Krische

Our laboratory has developed a broad, new family of stereo- and site-selective C-C couplings that merge the characteristics of catalytic hydrogenation and carbonyl addition. Hydrogenation or transfer hydrogenation of π-unsaturated hydrocarbons in the presence of carbonyl compounds or imines promotes C=X (X = O, NR) addition. In related hydrogen auto-transfer reactions, alcohols served dually as reductants and carbonyl proelectrophiles, enabling direct, enantioselective conversion of lower alcohols to higher alcohols. These methods streamline the synthesis of polyketide natural products, enabling studies of their biological properties. 

Highlighted Recent Publications

Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio- Diastereo and Enantioselectivity in Alcohol-Mediated C-C Couplings via Hydrogen Transfer 

Palladium(I)-Iodide Catalyzed Deoxygenative Heck Reaction of Vinyl Triflates: A Formate-Mediated Cross-Electrophile Reductive Coupling with cine-Substitution

Allyl Alcohol as an Acrolein Equivalent in Enantioselective C-C Coupling: Total Synthesis of Amphidinolides R, J, and S 

J. Am. Chem. Soc. 2024, 146, DOI: 10.1021/jacs.4c01857.

J. Am. Chem. Soc. 2023, 145, DOI: 10.1021/jacs.3c09876.

J. Am. Chem. Soc. 2023, 145, 8242 (DOI: 10.1021/jacs.3c01809). 

Social Media @Krischelab

H2-Mediated C-C Bond Formation

The formation of carbon-carbon (C-C) bonds is of fundamental significance. Research in the Krische laboratory demonstrates that C-C bond formation may be achieved under the conditions of catalytic hydrogenation and transfer hydrogenation. These studies represent the first systematic efforts to exploit hydrogenation in C-C couplings beyond hydroformylation and define a departure from the use of preformed organometallic reagents in carbonyl addition.

The Krische group reports that diverse π-unsaturated reactants reductively couple to carbonyl compounds and imines under hydrogenation conditions, thereby providing a byproduct-free alternative to stoichiometrically preformed organometallic reagents in a range of classical C=X (X = O, NR) addition processes. In such transformations, one simply hydrogenates two molecules in the presence of one another to form a single more complex product. This work evokes the question of whether all processes employing stoichiometric metallic reagents can be conducted catalytically under hydrogenative conditions.

More recently, by exploiting alcohols as both hydrogen donors and aldehyde precursors, byproduct-free carbonyl addition is achieved from the alcohol oxidation level. Such alcohol-unsaturated C-C couplings circumvent the redox manipulations often required to convert alcohols to aldehydes, and again bypass the barriers imposed by the use of stoichiometrically preformed organometallics. As chemical industry shifts from petrochemicals to renewable feedstocks, such direct byproduct-free couplings of alcohols are anticipated to find broad use.