Formaldehyde tert-butyl hydrazone as a formyl anion equivalent: asymmetric addition to carbonyl compounds

Abstract

The asymmetric 1,2-addition of formyl anion equivalents to carbonyl compounds is a powerful synthetic tool that ideally provide access to highly functionalizable a-hydroxy aldehydes in an enantioselective fashion. In this context, the nucleophilic character of formaldehyde hydrazones, together with their remarkable stability as monomeric species, has been exploited for the functionalization of diverse carbonyl compounds, using initially auxiliary-based methodologies and, more recently, catalytic enantioselective versions. This feature article highlights our research progress employing formaldehyde tert-butyl hydrazone as a versatile formyl anion equivalent, in combination with bifunctional H-bonding organocatalysis. The design and optimization of different catalytic systems, focusing on a dual activation of both reagents, is reviewed, as well as the racemization free unmasking of the formyl group and representative product transformations for the construction of valuable, densely functionalyzed chiral building blocks.