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

N-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, N-2 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.

Automated summary

This study presents a novel aluminum halide-mediated synthesis of N-haloalkenyl imidoyl halides, which is highly versatile and provides highly functionalized products. The reaction mechanism involves the opening of the triazole ring, N-2 elimination, and halide exchange reactions.