Highly Regioselective Modular Assembly of 3‑Phosphonyl Polysubstituted Pyridines through Radical Cascade Cyclization of 1,5-Enynes with Phosphine Oxide by Photoinitiation

A series of 3-phosphonyl polysubstituted pyridine were first synthesized by photocatalysis, combining a phosphonyl radical cascade reaction, Boc deprotection, and aromatization. This strategy can avoid the difficulties of activating the C3–H bond on pyridine to synthesize 3-phosphonylpyridine under mild conditions. Furthermore, by constructing different enynes, we can achieve the metal-free modular synthesis of 3-phosphonyl polysubstituted pyridine, which will be transferred into a new type of phosphine ligand. This is of significance for organometallic catalysis. The regioselective control and detailed reaction mechanism of the cascade reaction are explained by DFT calculations.