2 - Chiral Quaternary Ammonium Salts in Organocatalysis

Abstract

The acceleration of a reaction by means of a substoichiometric amount of small chiral organic molecules emerged as a powerful asymmetric synthetic methodology during the early 2000s. As testified by the increasing number of publications, organocatalysis has become the third pillar of catalysis beside metallocatalysis and biocatalysis. In a modern society looking for both efficient and environmentally benign processes, catalysis, especially when making use of usually environmentally benign organic-based catalysts, stands out when talking of a contemporary sustainable chemistry. The term organocatalysis was coined in 2000, along with the conceptualization of generic modes of activation allowing the classification of organocatalytic processes. Nevertheless, the occurrences of organic catalysts in synthesis dated back much before this period of time. Quaternary ammonium salts (R4N+X–) is a representative example of this nonlinear historical evolution. In the late 1960s, leading works by Starks, Makosza and Brändström established that amphiphilic quaternary phosphonium or ammonium salts, having long alkyl chains R, were able to accelerate a reaction occurring in a biphasic mixture, either solid/liquid or liquid/liquid immiscible phases. In 1971, Starks proposed the term “phase-transfer catalysis” (PTC) to account for the ability of R4N+ cation (i) to accelerate the transport a polar nucleophile Nu– species from one polar phase (a solid phase such as a mineral base or an aqueous phase) into a non-polar organic solvent (liquid 2) and (ii) to facilitate/accelerate the addition reaction to a given electrophile E+.