Kinetic Resolution of Ansa Cyclophanes by Peptide‐Catalyzed Aldol/Retro‐Aldol Reactions

Abstract

Kinetic resolution of a planar‐chiral ansa cyclophane, 13‐formyl‐1,11‐dioxa[11]paracyclophane, was conducted by a peptide‐catalyzed aldol reaction. With a resin‐supported tripeptide, d ‐Pro‐Tyr‐Phe, the resolution occurred in a moderate selectivity. It was also found that the racemic mixture of the aldol product could be resolved by a peptide‐catalyzed retro‐aldol reaction. By performing a consecutive kinetic resolution via the aldol reaction followed by the retro‐aldol reaction with the enantiopair of the tripeptide, the planar‐chiral aldol adduct was obtained in a good enantiopurity. The resin‐supported peptide catalysts could be easily removed from the reaction mixture and reused. Formyl‐substituted 1,10‐dioxa[10]paracyclophane and 1,10‐dithia[10]paracyclophane were also applicable for the resolution.