Chiral Phosphine Oxide-Catalyzed Enantioselective Transannular Bromoaminocyclization for the Synthesis of Tropanes

A chiral phosphine oxide-catalyzed enantioselective transannular bromoaminocyclization is developed for the enantioselective synthesis of tropane scaffolds. Under optimized conditions, various 5-aminocyclohept-1-enes are converted to 8-azabicyclo[3.2.1]octanes in excellent yields (up to 99%) and enantioselectivities (up to 99% ee). Gram-scale synthesis and derivatization proceed without a loss of stereochemical integrity. DFT calculations support a hydrogen-bonding-controlled mechanism. This strategy provides a concise route to chiral tropane derivatives.