Facile Domino Access to Chiral Bicyclo[3.2.1]octanes and Discovery of a New Catalytic Activation Mode

A highly enantio- and diastereoselective organocatalytic domino Michael−Henry process for the preparation of synthetically unique and medicinally important bicyclo[3.2.1]octane derivatives with four stereogenic centers including two quaternary stereocenters has been developed. Theoretical DFT calculations on the transition states have been carried out to reveal origins of the excellent stereoselectivities. A novel dual model was thus proposed.