Enantioselective Organocatalytic Aminomethylation of Aldehydes

Significance

A highly enantioselective amino­methylation of aldehydes is presented. The Mannich addition of aldehydes to a formaldehyde iminium ion is catalyzed by Jørgensen-Hayashi’s catalyst A and provides α-substituted β -amino aldehydes with moderate to good yields and excellent enantioselectivities. To avoid racemization, Mannich products were immediately reduced to the corresponding β -substituted γ-amino alcohols. Ionic interactions occurring during the transition state of the reaction are proposed to influence the stereo­chemical outcome and the use of 1 M LiCl leads to a moderate enantioselectivity enhancement. The β -substituted γ-amino alcohols generated via Mannich reaction/reduction could be successfully converted into ^β2-amino acids on a several-gram scale through a short and simple pathway.