4.12 Direct C–C Bond Formation (Henry, aza-Henry)

Abstract

Nitroalkanes react with either carbonyl compounds (Henry reaction) or imines (aza-Henry reaction) to produce β-hydroxy-nitro compounds or β-amino-nitro compounds, respectively, under mild conditions. The first catalytic enantioselective Henry reaction was reported in1992, promoted by a rare earth–lithium–BINOL complex (LnLB, where Ln=lanthanoid, L=lithium, and B=BINOL derivative). In this catalysis, the dual activation of both of the substrates is responsible to achieve high catalytic efficiency. Namely, the rare earth metal in the LnLB complex acts as Lewis acid, and the lithium binaphtholate moiety acts as Bronsted base. Other chiral metal catalysts containing zinc, copper, etc. and chiral organocatalysts having thiourea and guanidine moiety are also reported. In these enantioselective catalysts, the dual activation mechanism seems to be indispensable to obtain the nitroaldol adducts in high enantiocontrol. Syn- and anti-selective asymmetric Henry reactions are also realized and applied to the synthesis of pharmaceutically important compounds and natural products.