Photoinduced Copper-Catalyzed Regio- and Diastereoselective Multicomponent [3 + 2 + 1] Radical Cyclization To Access Tetrahydropyridines.

The use of simple raw materials to construct complex piperidine scaffolds via multicomponent reactions is highly desirable from the perspectives of atom and step-economy. In this Letter, we present a photoinduced copper-catalyzed three- or four-component [3 + 2 + 1] radical cyclization, utilizing inexpensive and readily available feedstock amines, alkynes, and aldehydes, to synthesize multisubstituted bicyclic or spirocyclic tetrahydropyridines. This method is notable for its mild conditions, atom-economic approach, excellent regio- and diastereoselectivity, and the simultaneous activation of two α-amino C(sp3)-H bonds, resulting in the formation of three C-C bonds and one C-N bond in a single step. Mechanistic studies suggest that the α-aminoalkyl radical is the key intermediate in this reaction, which undergoes sequential radical addition, 1,5-HAT, and 6-exo-trig-type radical cyclization.