Organic Chemistry Seminar

We have designed an enantioselective coupling of N-alkylamines and a,b-unsaturated compounds by implementing the cooperative action of two Lewis acid catalysts that possess overlapping functions. We have achieved this by developing catalyst/substrate combinations that form frustrated Lewis pairs (FLPs), namely, active acids and bases whose mutual quenching (formation of "classic" Lewis adduct) is sterically precluded. By tuning of different features of structurally and electronically different Lewis acids and substrates, the ability of Lewis acid catalysts to serve as a hydride acceptor from amines, or an activator of a,b-unsaturated compounds towards borohydride reduction to afford a chiral enolate, can be adjusted. Accordingly, enhancements in both the efficiency and stereoselectivity of C–C bond forming reactions between amines and a,b-unsaturated compounds can be attained without concomitant loss in enantioselectivity arising from any undesirable mode of catalysis by the achiral Lewis acid component. These principles serve as a conceptual framework for the development of new processes that demand separate and independently operational Lewis acidic co-catalysts whose functions might overlap and the simultaneous use may have a negative impact on enantioselectivity.