Highly Enantioselective Synthesis of Planar-Chiral Cyclophanes through a Brønsted Acid-Catalyzed Asymmetric Transfer Hydrogenation

Planar-chiral cyclophanes have received increasing attention for drug discovery due to their unique properties arising from the conformational strain. However, the catalytic asymmetric synthesis of planar-chiral cyclophanes is one of the long-standing challenges in chemistry. We herein report a Bronsted acid-catalyzed asymmetric transfer hydrogenation (ATH) reaction of cyclophane-derived imines, providing the planar-chiral cyclophanes in good yields (up to 98%) and with high enantioselectivities (up to >99% ee). The mutable ansa bridge allows the ATH reaction to occur through a kinetic resolution or a dynamic kinetic resolution process. The [11]-[14]-cyclophanes bearing an appropriate benzene ring substituent undergo a KR process, while [15]-[17]-cyclophanes undergo the ATH reaction in a DKR manner. Controlled experiments were performed to understand the reaction mechanism and origin of enantioselectivity.