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

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. Peptide‐catalyzed aldol and retro‐aldol reactions were applied to kinetic resolution of planar‐chiral ansa cyclophanes. By performing these reactions sequentially with the enantiopair of resin‐supported tripeptides, the aldol product could be obtained in a good enantiopurity.