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

Abstract

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, 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.

Access to Fluoroalkylated Azoles and 2-Acylaminoketones via Anhydride-Mediated Cleavage of NH-1,2,3-Triazoles

“…We have recently reported that transannulation efficiently proceeds for N-fluoroalkylated triazoles, [16][17][18][19] which allowed to overcome the limitation of the presence of sulfonyl group. Moreover, a ring cleavage of electron-deficient triazoles in the presence of Brønsted and Lewis acids, proceeding via a vinyl cation intermediate, was reported by our [20][21][22] and other 23 groups. However, the preparation of N-sulfonyl and N-fluoroalkyl triazoles requires multiple synthetic steps.…”

Stereoselective Synthesis of (Z)-β-Enamido Fluorides from N-Fluoroalkyl- and N-Sulfonyl-1,2,3-triazoles

“…9−13 Recently, we have showcased a new type of reactivity specific to N-fluoroalkyl-1,2,3-triazoles in the presence of strong Brønsted 14 or Lewis acids. 15 In comparison to rhodium-catalyzed reactions utilizing heating-induced ring opening and rhodium carbene formation, acid-mediated transformations proceed via protonation or coordination of N(1) on the triazole ring leading to diazonium salt 5, which upon nitrogen elimination forms vinyl cation 6. Delivering the (pseudo)halogen takes place from the same side as the fluoroalkyl-bound nitrogen, making the reaction highly stereoselective with respect to the Z stereoisomer (Figure 1B).…”

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

“…B: Ligand-controlled stereoselective synthesis of β,β-diaryl-substituted enamides. pling reactions with retention of configuration on the double bond and served as valuable starting materials for the synthesis of functionalized β,β-disubstituted enamides (Scheme 1A) [21,23].…”

“…Recently, we have reported a triflic acid-mediated reaction of N -fluoroalkyl-1,2,3-triazoles leading to ( Z )-β-enamido triflates [ 21 ] and Lewis acid-mediated reaction to ( Z )-β-enamido fluorides [ 22 ] and halovinyl imidoyl halides [ 23 ]. In addition, Li and co-workers extended the scope of accessible ( Z )-β-enamido triflates by denitrogenative reaction of N 1- H -1,2,3-triazoles in the presence of acyl halides and sodium triflate [ 24 ].…”

“…In addition, Li and co-workers extended the scope of accessible ( Z )-β-enamido triflates by denitrogenative reaction of N 1- H -1,2,3-triazoles in the presence of acyl halides and sodium triflate [ 24 ]. These enamido triflates and halides were found to undergo cross-coupling reactions with retention of configuration on the double bond and served as valuable starting materials for the synthesis of functionalized β,β-disubstituted enamides ( Scheme 1A ) [ 21 , 23 ].…”