Catalytic C-C Bond Forming Hydrogenations

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Project Summary: As exemplified by the Haber-Bosch reaction, which sustains half the human population, and enantioselective hydrogenation, which (beyond resolution of racemates) is the foremost chemical method used to create chiral pharmaceutical and agrochemical ingredients, catalytic hydrogenation has had a greater impact on humanity than any other chemical process. Prior to our work, the sole example of a “C-C bond forming hydrogenation” was hydroformylation, which is now the largest application of homogenous metal catalysis. My laboratory has pioneered a broad, new family of metal-catalyzed carbonyl reductive couplings that exploit feedstock pronucleophiles in combination with safe, inexpensive feedstock reductants (H2, 2- PrOH, HCO2H), and related H2-autotransfer processes (ROH = reductant & proelectrophile) that directly convert lower alcohols to higher alcohols. These transformations bypass stoichiometric organometallic reagents and the issues of safety, selectivity, and waste associated with their use, offering a byproduct-free alternative to a range of classical carbonyl or imine additions. In the proposed funding period, this reactivity pattern will be extended to couplings of α-olefins and C-X pronucleophiles, the use of amine proelectrophiles, the formation of quaternary stereocenters and use of base metal catalysts. Our ultimate objective is to develop environmentally benign methods for the conversion of inexpensive chemical feedstocks to value- added building blocks for use in the manufacture of pharmaceutical and agrochemical ingredients.