Diastereoselective Henry Reaction Catalyzed by Guanidine-Thiourea Bifunctional Organocatalyst

A highly diastereoselective Henry reaction (diastereo­mer ratio of 84:16 to 99:1) of (alpha)-substituted aldehydes with nitromethane was developed using guanidine-thiourea bifunctional catalyst 1. N,N-Dibenzyl-protected (alpha)-amino aldehydes (2a, 2d-h) and (alpha)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.