The Interplay of Invention, Observation, and Discovery in the Development of Lewis Base Activation of Lewis Acids for Catalytic Enantioselective Synthesis

Abstract

A review. This chapter chronicles the evolution of a paradigm shift in the conceptualization and development of chiral Lewis base catalysis of carbonyl addn. reactions with organosilicon nucleophiles. Prior to 2000, these reactions were exclusively practiced through the agency of highly electrophilic silicon species such as allyltrichlorosilanes and enoxytrichlorosilanes derived from aldehydes, ketones, and esters. However, a serendipitous discovery made during the development of these processes led to a fundamentally new insight, namely, that silicon tetrachloride could be activated by chiral Lewis bases (primarily phosphoramides) and the resulting chiral silicenium ion could serve as a general and effective catalyst for the addn. of many different enoxysilane nucleophiles derived from aldehydes, ketones, esters, nitriles, protected cyanohydrins, conjugated esters and amides, and isocyanides. In addn. to providing high generality, high yield, and high stereoselectivity, the new family of Lewis base-catalyzed reactions could be investigated mechanistically, and the foundations of reactivity and selectivity could be revealed. An anal. of how this paradigm shift occurred and the circumstances that led to discovery were described. [on SciFinder(R)]