α-Substituted vinyl azides: an emerging functionalized alkene

Abstract

Vinyl azides are highly versatile synthons that provide access to numerous N-heterocycles and other functional groups. α-Substituted vinyl azides (azido vinylidenes) are a special class that display unique reactivity, able to react not only as azides, but also as radical acceptors, enamine-type nucleophiles, and even electrophiles, thus delivering a wide range of nitrogen-containing compounds and their derivatives. An impressive variety of intermediates - such as iminodiazonium ions, nitrilium ions, iminyl radicals, and metal enaminyl radicals - can be generated from vinyl azides and exploited in cycloadditions, C-H functionalizations, hydrolysis processes, and cascade reactions under transition metal/photoredox catalysis. In addition to presenting synthetic protocols to access vinyl azides, this Review offers a comprehensive coverage of the development of their multifaceted reactivity, and highlights their potential as versatile precursors for synthetic applications.

Scandium (III)‐Catalyzed Cycloaddition of in situ Generated ortho‐Quinone Methides with Vinyl Azides: An Efficient Access to Substituted 4H‐Chromenes

“…In this context, we envisioned that using vinyl azides as a masked alkyne source which would go through [4 + 2] cycloaddition with o-QMs to form anazido chromane intermediate,concomitant elimination of hydrazoic acidafford the desired chromenes(Scheme 1B). [11] Most commonly, vinyl azides produce vinyl nitrene intermediates by thermal decomposition or photolysis and thus act as a three atom CÀCÀN synthon in cycloaddition reactions. [11] Most commonly, vinyl azides produce vinyl nitrene intermediates by thermal decomposition or photolysis and thus act as a three atom CÀCÀN synthon in cycloaddition reactions.…”

Oxidative Fluorocyclization of Vinyl Azides Leading to 5‐Azido,5‐fluoro‐1,3‐oxolan‐2‐one

“…moiety acts as an in situ formed leaving group. Building from our long understanding efforts in the chemistry of α-vinyl azides, [8] we here report an oxidative fluorocyclization of vinyl azides with in situ generated difluoroiodobenzene from PIDA and Py·HF. [7] It is the first example of intermolecular oxyfluorination of vinyl azides.…”

“…Switching to other potential fluorine sources (e.g. Et 3 N·HF, [9] AgF, [10] CsF [11] ), led to no reaction (entries [6][7][8]. A brief survey of other solvents revealed poor or no conversion in DMF, DMSO and CHCl 3 (entries 9-11); similarly, lowering the reaction temperature to -40 or -20°C led to reduced yields (entries 12-14).…”

“…3-Phenylcyclobutanol and cyclopentyl alcohol were successfully subjected to this transformation with 70 % and 85 % yield (2b, 2d), respectively. Cyclohexyl alcohols tethered with different functional groups also suitable to give the desired fluorocyclization products (2, [4][5][6][7][8][9][10][11] with good to excellent yields (80-93 %). Also, the use of tetrahydropyran derivative leading to the desired product 2n in an 94 % yield.…”

Bimetal‐Catalyzed Cascade Reaction for Efficient Synthesis of N‐Isopropenyl 1,2,3‐Triazoles via In‐Situ Generated 2‐Azidopropenes

“…Recently, we have developed two cascade reactions with readily available vinyl azides to assemble functionalized N ‐heterocycles under copper‐mediated system. Owing to our ongoing efforts to explore novel reactions based on vinyl azides . We herein report, the first example, a one‐pot protocol for the synthesis of N ‐isopropenyl 1,2,3‐triazoles under mild reaction conditions, which involves the generation of 2‐azidopropenes in situ by selective C(sp 3 )‐OAr bond cleavage to conduct click reaction with high yields (Scheme d).…”