Haloalkenyl Imidoyl Halides as Multifacial Substrates in the Stereoselective Synthesis of N‐Alkenyl Compounds

Abstract

AbstractN‐Alkenyl compounds are versatile synthetic building blocks and their stereoselective transformations are key processes in the synthesis of many prominent classes of natural products, pharmaceuticals, and agrochemicals. However, a large structural variety of known N‐alkenyl compounds and their diverse reactivity have so far precluded the development of a general method for their stereoselective synthesis. Herein we present an aluminum halide‐mediated, highly stereoselective, efficient and scalable transformation of commercially available N‐fluoroalkyl‐1,2,3‐triazoles to N‐haloalkenyl imidoyl halides, and demonstrate their use in the synthesis of stereodefined N‐alkenyl amides, amidines, imines, hydrazonoamides, imidothioates, iminophosphonates, 1,2,4‐triazoles and tetrazoles. The reaction is of wide scope on both the triazole substrate and aluminum halide, providing highly functionalized products. Mechanistic and computational investigations suggest a reaction mechanism involving the triazole ring opening, initiated by the coordination of nitrogen one of the triazole ring to the Lewis acid, N2 elimination and the formation of a vinyl cation intermediate, which reacts with nitrogen‐bound aluminum halide, followed by a series of halide exchange reactions on C−X and Al−X bonds.magnified image