Photoinduced Pd-Catalyzed Formal Asymmetric Allylic Substitution of Piperidine Scaffolds

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.