Catalytic Asymmetric Addition Reactions of Formaldehyde N,N-Dialkylhydrazone to Synthesize Chiral Nitrile Derivatives.

A number of nitrile-containing chiral molecules were synthesized via asymmetric nucleophilic addition of formaldehyde N,N-dialkylhydrazone as the nitrile equivalent. Chiral N,N'-dioxide/metal salt complexes enabled the asymmetric addition reactions to both isatin-derived imines and α,β-unsaturated ketones, generating amino nitriles and 4-oxobutanenitrile derivatives in good yields with high enantioselectivities. This protocol was highlighted by avoiding the use of toxic nitrile reagents, wide substrate scope, and versatile transformations of chiral hydrazone adducts into other valuable molecules.