Synthesis of 3-Amino-1-(difluoromethylidene)tetralins via Relay Photocatalytic Cascade Reactions of Arylalanines and 2-Bromo-3,3,3-trifluoropropene

A relay photocatalytic cascade reaction for the synthesis of 3-amino-1-(difluoromethylidene)tetralins was described. The reaction used readily available N-Boc protected arylalanines and bulk industrial chemical 2-bromo-3,3,3-trifluoropropene (BTP) as the starting materials combining two photoredox catalytic cycles with a single photocatalyst. In the first catalytic cycle, the defluorinative coupling of N-Boc arylalanines with BTP provided 2-bromo-1,1-difluoroalkenes. In the second catalytic cycle, 2-bromo-1,1-difluoroalkenes underwent intramolecular radical cyclization by photoredox activation of C(sp(2))-Br bond, affording the desired 3-amino-tetralins bearing an exo-difluoroethylene unit in good yields. Moreover, the reactions of 3-aryl propanoic acids and BTP for the construction of 1-(difluoromethylidene)tetralins were also demonstrated.