Synthetic Methods & Natural Product Synthesis at the University of Texas at Austin
Synthetic Methods & Natural Product Synthesis at the University of Texas at Austin
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Principal Investigator:
Professor Michael J. Krische
Our laboratory has pioneered the use of hydrogenation and transfer hydrogenation in catalytic C-C bond formation, enabling a departure from the use of premetalated reagents in chemical synthesis. Additionally, we have developed hydrogen auto-transfer reactions that affect direct stereo- and site-selective conversion of lower alcohols to higher alcohols. Training in Krische laboratory encompasses enantioselective catalysis, organometallic and synthetic chemistry, including natural product total synthesis.
Highlighted Recent Publications
Total Synthesis and Structural Revision of the Phenylnaphthacenoid Type II Polyketide Antibiotic Formicamycin H via Ruthenium-Catalyzed Hydrogen Auto-Transfer [4+2] Cycloaddition
Enantioselective N-Heteroaryl C-H Functionalization for Piperidine-Azine Conjugation: Alkynes as Allylmetal Pronucleophiles in Dearomative Addition-Hydrogen Auto-Transfer
Aryl Halide Cross-Coupling via Formate-Mediated Transfer Hydrogenation
J. Am. Chem. Soc. 2024, 146, 26351. (DOI: org/10.1021/jacs.4c09068.)
J. Am. Chem. Soc. 2024, 147. (DOI: 10.1021/jacs.4c15157.)
J. Am. Chem. Soc. 2023, 146, 7905. (DOI: 10.1021/jacs.4c01857)
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.
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