Enantioselective organo-singly occupied molecular orbital catalysis: the carbo-oxidation of styrenes.

A critical objective for the continued advancement of the field of asymmetric catalysis is the design and implementation of novel activation modes that allow the invention of unprecedented transformations. Recently, our laboratory introduced a new mode of organocatalytic activation, termed (singly occupied molecular orbital) SOMO catalysis, that is founded upon the transient production of a 3π-electron radical-cation species that can function as a generic platform of induction and reactivity. As part of these studies, we documented the first direct and enantioselective allylic alkylation, enolation, and vinylation of aldehydes, three protocols that were not previously known in a chiral or achiral format. Continuing this theme, we recently questioned whether feedstock olefins, such as styrenes, might be exploited in this SOMO pathway to allow the enantioselective R-homobenzylation of aldehydes, a new C-C bond-forming reaction between functional groups that are generally inert to chemical combination. In this context, we disclose the first asymmetric SOMO-catalyzed carbo-oxidation of styrenes to provide γ-nitrate-R-alkyl aldehydes, a valuable synthon for the production of enantioenriched butyrolactones, pyrrolidines, and R-formyl homobenzylation adducts. Most important, this new organo-SOMO reaction allows simple styrenes to function as R-alkylation partners for aldehydes, a transformation that to our knowledge is without precedent.