Abstract: Low molecular weight, chiral organic molecules possessing distinct hydrogen-bond donor motifs have been shown to catalyze an array of C–C and C–heteroatom bond-forming reactions with high enantioselectivity and broad substrate scope. In particular, dual hydrogen bond donors such as ureas, thioureas, squaramides, and guanidinium ions have been studied in detail in the context of electrophile activation. These catalysts have been shown to operate by either of two, fundamentally different modes of electrophile activation: 1) direct hydrogen bonding to a neutral electrophile, and 2) anion binding to generate chiral ion pair. We have applied both reactivity concepts to several classes of electrophiles that have presented long-standing challenges to asymmetric catalysis.
In this lecture, I will describe recent advances in my group’s development and elucidation of catalytic anion-abstraction processes. These investigations have revealed unexpected pathways underlying catalytic nucleophilic substitution reactions, and the insights have been applied to the discovery of new catalysts for stereospecific glycosylation and enantioselective SN1 pathways.