Event

Hydrogen-Mediated C-C Bond Formation

Stereo- and site-selective methods for the byproduct-free modification of unprotected organic compounds that occur through the addition or redistribution of hydrogen are natural endpoints in the advancement of methods for efficient, green chemical synthesis.1 Progress toward this goal requires a departure from reactants that embody non-native structural elements, such as premetalated reagents, directing/protecting groups and chiral auxiliaries. Our laboratory has developed a broad, new family of reductive C-C bond formations that merge the characteristics of catalytic hydrogenation and carbonyl addition.2 Hydrogenation or transfer hydrogenation of π-unsaturated reactants in the presence of C=X (X = O, NR) bonds delivers products of carbonyl or imine addition. In related hydrogen auto-transfer reactions, alcohols served dually as reductants and carbonyl proelectrophiles, enabling direct conversion of lower alcohols to higher alcohols.3 Such hydrogen-mediated C-C bond formations contribute to a departure from the use of stoichiometric organometallic reagents, and the issues of safety, selectivity, and waste posed by their use.[1]-4

([1]) “Feedstock Reagents in Metal-Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target-Oriented Synthesis,” Doerksen, R. S.; Meyer, C. C.; Krische, M. J. Angew. Chem. Int. Ed. 2019, 58, 14055.

(2) “Unlocking Hydrogenation for C-C Bond Formation: A Brief Overview of Enantioselective Methods,” Hassan, A.; Krische, M. J. Org. Proc. Res. Devel. 2011, 15, 1236.

(3) “Catalytic Enantioselective Carbonyl Allylation and Propargylation via Alcohol Mediated Hydrogen Transfer: Merging the Chemistry of Grignard and Sabatier,” Kim, S. W.; Zhang, W.; Krische, M. J. Acc. Chem. Res. 2017, 50, 2371.

(4) “Metal Catalyzed Reductive Coupling of Olefin-Derived Nucleophiles: Reinventing Carbonyl Addition,” Nguyen, K. D.; Park, B. Y.; Luong, T.; Sato, H.; Garza, V. J.; Krische, M. J. Science 2016, 354, 300 (aah5133).