Synthesis of β‐Hydroxyaldehydes with Stereogenic Quaternary Carbon Centers by Direct Organocatalytic Asymmetric Aldol Reactions

Abstract

A fluorescence detection system was used to identify effective chiral-amine/acid combinations as bifunctional catalysts for asymmetric direct catalytic aldol reactions of α,α-dialkyl aldehydes with aryl aldehydes (see scheme). With the optimized catalyst system, the reaction of isobutyraldehyde with p-nitrobenzaldehyde provided the α,α-dimethyl aldol product in 92 % yield with 96 % ee. R1, R2=alkyl; X=NO2, CN, Br, Cl, OMe, H.