Photo-driven Enantioselective 6-endo Hydroaminative Cyclization

Chiral 3,4-dihydroisoquinolones are essential scaffolds in bioactive alkaloids. This Synpacts highlights a recently developed photo-driven enantioselective 6-endo hydroaminative cyclization using a chiral C2-symmetric arylthiol HAT catalyst. Mechanistic studies reveal that the reaction proceeds via a radical cation intermediate, where 6-endo cyclization is kinetically favored over the 5-exo pathway. By suppressing deprotonation, high regio- and enantioselectivity were achieved. This methodology enables the formal synthesis of complex alkaloids and emphasizes the importance of understanding radical cation reactivity for developing novel site-selective transformations in organic synthesis.