Photoinduced Pd-Catalyzed Formal Asymmetric Allylic Substitution of Piperidine Scaffolds

Abstract

Transition-metal-catalyzed asymmetric allylic substitution (AAS) reaction is one of the most synthetically useful and powerful reactions for the assembly of carbon–carbon and carbon–heteroatom bonds in an asymmetric fashion. Herein, we accomplished a photoinduced, palladium-catalyzed formal AAS reaction without preinstalling the allylic structural unit, which rationally integrates photocatalytic desaturation and asymmetric allylic substitution. A series of sterically congested optically pure 2-alkyltetrahydropyridine scaffolds were facilely prepared from inexpensive and readily available piperidine derivatives with carbon-centered nucleophiles, with excellent compatibility (51 examples), high efficiency (up to 96% yield), excellent regioselectivity (only α-product), and outstanding enantioselectivities (up to 95.5:4.5 er). Comprehensive computational studies rationalized the compatibility of photoinduced radical chemistry and transition-metal-catalyzed AAS reaction and disclosed the origin of regioselectivity and enantioselectivity.