First asymmetric nucleophilic displacement reactions on chiral α-substituted aldehyde hydrazones

The first asymmetric nucleophilic substitution reaction on racemic alpha-substituted aldehydes using enantiomerically pure hydrazines as chiral auxiliaries is presented. The diastereoselectivity of the process is achieved by a dynamic kinetic resolution via the 1:1 epimeric mixture of the substrate hydrazones. The a(2)-reactivity (Umpolung) of the alpha-substituted hydrazones is accomplished by complexation with Lewis acids. Several carbon-, sulfur- and oxygen-nucleophiles were shown to readily undergo substitution of the alpha-leaving group under these conditions, affording the substitution products with good to excellent chemical yields and with low to moderate diastereoselectivities. Two methods for the cleavage of the chiral auxiliary are described. (C) 1998 Eisevier Science Ltd. All rights reserved.