Direct and Enantioselective Organocatalytic α-Chlorination of Aldehydes

The first direct enantioselective catalytic α-chlorination of aldehydes has been accomplished. The use of enamine catalysis has provided a new organocatalytic strategy for the enantioselective chlorination of aldehydes to generate α-chloro aldehydes, an important chiral synthon for chemical and medicinal agent synthesis. The use of imidazolidinone 3 as the asymmetric catalyst has been found to mediate the halogenation of a large variety of aldehyde substrates with the perchlorinated quinone 1 serving as the electrophilic chlorinating reagent. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. The capacity of catalyst 3 to override the inherent bias of resident stereogenicity in the chlorination of enantiopure β-chiral aldehydes is also described. Catalyst quantities of 5 mol % were generally employed in this study.