Alkenes cyclic nitronate preparation

Elsewhere, Heaney et al. (313-315) found that alkenyloximes (e.g., 285), may react in a number of ways including formation of cyclic nitrones by the 1,3-APT reaction (Scheme 1.60). The benzodiazepinone nitrones (286) formed by the intramolecular 1,3-APT will undergo an intermolecular dipolar cycloaddition reaction with an external dipolarophile to afford five,seven,six-membered tricyclic adducts (287). Alternatively, the oximes may equilibrate to the corresponding N—H nitrones (288) and undergo intramolecular cycloaddition with the alkenyl function to afford five,six,six-membered tricyclic isoxazolidine adducts (289, R = H see also Section 1.11.2). In the presence of an electron-deficient alkene such as methyl vinyl ketone, the nitrogen of oxime 285 may be alkylated via the acyclic version of the 1,3-APT reaction and thus afford the N-alkylated nitrone 290 and the corresponding adduct 291. In more recent work, they prepared the related pyrimidodiazepine N-oxides by oxime-alkene cyclization for subsequent cycloaddition reactions (316). Related nitrones have been prepared by a number of workers by the more familiar route of condensation with alkylhydroxylamines (Scheme 1.67, Section 1.11.3). 

As part of an extensive study of the 1,3-dipolar cycloadditions of cyclic nitrones, Ali et al. (392-397) found that the reaction of the 1,4-oxazine 349 with various dipolarophiles afforded the expected isoxazolidinyloxazine adducts (Scheme 1.78) (398). In line with earlier results (399,400), oxidation of styrene-derived adduct 350 with m-CPBA facilitated N—O cleavage and further oxidation as above to afford a mixture of three compounds, an inseparable mixture of ketonitrone 351 and bicyclic hydroxylamine 352, along with aldonitrone 353 with a solvent-dependent ratio (401). These workers have prepared the analogous nitrones based on the 1,3-oxazine ring by oxidative cleavage of isoxazolidines to afford the hydroxylamine followed by a second oxidation with benzoquinone or Hg(ll) oxide (402-404). These dipoles, along with a more recently reported pyrazine nitrone (405), were aU used in successful cycloaddition reactions with alkenes. Elsewhere, the synthesis and cycloaddition reactions of related pyrazine-3-one nitrone 354 (406,407) or a benzoxazine-3-one dipolarophile 355 (408) have been reported. These workers have also reported the use of isoxazoles with an exocychc alkene in the preparation of spiro[isoxazolidine-5,4 -isoxazolines] (409). 

Stereoselective cycloaddition between functionalized six-membered cyclic nitrone 166 derived from o-lyxose and sugar alkenes was employed for the synthesis of aza-C-disaccharides [72]. Reaction of nitrone 166 and alkene 167 prepared from methyl a-o-mannopyranoside in toluene at reflux led to the isolation of a crystalline cycloadduct 168 in 84% yield. The isoxazohdine 168 was acetylated and cleaved using Mo(CO)6. This was followed by deoxygenation and routine deprotection to give the aza-C-disaccharide 169, isolated as its hydrochloride (44% overall from 168). 

Phenylthio)mtromethane has been dehydrated and the resultant phenylthionitrile oxide trapped with alkenes to provide isox-azohnes (eq 10). These compounds are convenient precursors for 3-(phenylsulfonyl)isoxazolines and -hydroxy ketones. The cycloaddition-H ing contraction of ynamines with 1-nitro-l-phenylthioalkenes has been used to prepare cyclic nitrones (eq 11)."... 

Nitrones can undergo a variety of synthetically useful reactions 1,3-dipolar cycloaddition with alkenes and allqmes to isoxazolidines, nucleophilic addition which provide hydrojgrlamines, or Sm mediated cross couplings with carhonyl compounds affording vicinal amino alcohols.Recently, special attention is focused on the preparation and application of the optically pure cyclic nitrones, being used in the synthesis of biologically important molecules. ... 

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