Synthesis of enantioenriched α-heteroatom functionalised aldehydes by chiral organocatalysis and their synthetic applications

Abstract

Asymmetric organocatalysis has proven to be one of the most versatile methods for the enantioselective α-functionalisation of aldehydes. Initially pioneered by the report of an L-proline catalysed intermolecular aldol reaction, the field has seen a diversification in the range of catalysts as well as heteroatomic modifications at the α-stereocenter. From the original reports of these synthetic procedures, additional focus has been on understanding the catalytic cycle and mechanism of reaction. This has led primarily to the development of novel catalysts with superior chemoselectivity and better understanding of catalyst deactivation pathways. Additionally, the demand and synthetic scope for chiral α-heteroatom substituted aldehydes is examined in the three general synthetic applications: the Horner–Wadsworth–Emmons, aldol and organometallic addition reactions. In each of these example applications common examples of functional group chemistry and their downstream reactivities are reviewed. Interesting total synthesis applications are also highlighted.