Stereospecific Formal [3+2] Dipolar Cycloaddition of Cyclopropanes with Nitrosoarenes: An Approach to Isoxazolidines

Abstract

The MgBr2-catalyzed formal [3+2] cycloaddition of donor-acceptor activated cyclopropanes with nitrosoarenes offers a novel approach to various structurally diverse isoxazolidines. The reactions, which are experimentally easy to conduct, occur with complete stereospecificity and perfect control of regioselectivity. Product isoxazolidines can be readily transformed into α-amino lactones by reductive or decarboxylative N-O cleavage and subsequent lactonisation, and the N-aryl bond cleavage is also possible under oxidative conditions.

Dearomatization of electron poor six-membered N-heterocycles through [3 + 2] annulation with aminocyclopropanes

“…6 In particular, these reactions are highly successful with enol-ethers, 7 nitrosoarenes, 8 imines, 9 heteroatom substituted alkynes, 10 carbonyl compounds 11 and nitrones. 12 However, dearomative [3 + 2] annulation reactions were only intensively studied with indoles 13 and a single example was reported for benzothiazoles (Scheme 2).…”

Catalyst‐Free Regioselective [3+2] Cycloadditions of α,β‐unsaturated N‐arylnitrones with Alkenes to Access Functionalized Isoxazolidines: A DFT Study

“…Therefore, it is not surprising that great effort has been devoted to the development of novel, efficient and practical methods for the construction of isoxazolidines including cycloadditions [13][14][15][16] , annulation 17 , cascade reaction, 18 and others 19 (Scheme 1a). For instance, Jorgensen and co-workers reported the first cascade 1,3-dipolar cycloaddition on the remote olefin with good to excellent regio-and stereo-selectivity by iminium-ion activation process with a secondary amine catalyst.…”

Copper‐Catalyzed Three‐Component Annulations of Alkenes, Nitrosoarenes, and N‐Hydroxyallylamines To Form Fused Oxazinane/Isoxazolidine Heterocycles

“…We also performed a reductive cleavage on compound 5 a to afford a seven‐membered heterocycle 9 c stereoselectively; the structure was assigned based on a comparison with the 13 C NMR data of compounds 9 a and 9 b . To increase their utility, we developed a selective N−O cleavage of these products using Zn/AcOH in THF, as manifested by compounds 8 c and 4 a , which undergo a single N−O cleavage selectively at their isoxazolidine ring to form products 9 d and 9 f stereoselectively. These structures were confirmed by X‐ray diffraction…”