Zinc‐Catalyzed Asymmetric Formal [4+3] Annulation of Isoxazoles with Enynol Ethers by 6π Electrocyclization: Stereoselective Access to 2H‐Azepines

Abstract

6p electrocyclization has attracted interest in organic synthesis because of its high stereospecificity and atom economy in the construction of versatile 5-7-membered cycles. However,e xamples of asymmetric 6p electrocyclization are quite scarce,a nd have to rely on the use of chiral organocatalysts,a nd been limited to pentadienyl-anion-and trienetype 6p electrocyclizations.D escribed herein is az inc-catalyzed formal [4+ +3] annulation of isoxazoles with 3-en-1-ynol ethers via 6p electrocyclization, leading to the site-selective synthesis of functionalized 2H-azepines and 4H-azepines in good to excellent yields with broad substrate scope.Moreover, this strategy has also been used to produce chiral 2H-azepines with high enantioselectivities (up to 97:3 e.r.). This protocol not only is the first asymmetric heptatrienyl-cation-type 6p electrocyclization, but also is the first asymmetric reaction of isoxazoles with alkynes and the first asymmetric catalysis based on ynol ethers. Scheme 1. Asymmetric 6p electrocyclization.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Copper‐Catalyzed Azide–Ynamide Cyclization to Generate α‐Imino Copper Carbenes: Divergent and Enantioselective Access to Polycyclic N‐Heterocycles

“…of 90.5:9.5 was achieved by using L7 as chiral ligand (entry 7). [21] Other solvents such as DCM and CHCl 3 were also investigated, but failed to improve the enantioselectivity (entries 10 and 11). Theu se of NaBAr F 4 (12 mol %) as additive or Cu(CH 3 CN) 4 BF 4 (10 mol %) as catalyst led to slightly decreased enantioselectivities (entries 12 and 13).…”

Overview of 6π 1,5‐Electrocyclization over the Past 40 Years

“…The 6π electrocyclization reaction can be divided into three types which can construct 5—7 membered rings, respectively (Scheme 1). [ 4 ]…”

An unexpected synthesis of azepinone derivatives through a metal-free photochemical cascade reaction

“…In this context, a series of reagents, including azides, 2H-azirines, isoxazole derivatives, aza-pyridium ylides and sulfilimines, were elegantly designed 14 . Methods for preparing azaheterocycles based upon transition metal-catalyzed nitrene transfer from these nitrene equivalents to functionalized alkynes have been frequently reported by Liu [15][16][17] , Ye [18][19][20][21] , Hashmi 22,23 , and others 14 . The direct generation of nitrene intermediates, generally promoted by photoirradiation, high temperatures or transition metal catalysts, allows to form C − N bonds, including C − H amination, C − H amidation and alkene aziridation [24][25][26][27] .…”