Diastereoselective henry reaction catalyzed by guanidine-thiourea bifunctional organocatalyst

A highly diastereoselective Henry reaction (diastereomer ratio of 84:16 to 99:1) of α-substituted aldehydes with nitromethane was developed using guanidine-thiourea bifunctional catalyst 1. N,N-Dibenzyl-protected α-amino aldehydes (2a, 2d-h) and α-hydroxy aldehydes protected as silyl ethers (2i-j) were suitable substrates. The matched combination of this catalytic system, i.e., S-aldehydes and (R,R)-1 catalyst, can be understood in terms of the transition state of the asymmetric version of the Henry reaction catalyzed by 1.