Nitrile oxide, Benzo

There are a few communications concerning cycloadditions of nitrile oxides to unsaturated oxa and aza cage systems. Benzo- and mesitonitrile oxides RCNO give, with five substituted 7-oxanorbomenes 106, mixtures of the corresponding exo-adducts 107 and 108 in nearly quantitative yields. No traces of compounds resulting from the endo-face attack was detected (274). Substituents at positions 5 and 6 of 106 render the process highly regioselective. 

Mesitonitrile oxide, but not benzonitrile oxide, adds to aza-analogs of phenan-threne, viz., benzo[/z]quinoline, 1,10-, 1,7-, and 4,7-phenanthrolines to give low yields of mono-cycloadducts at the C(5)=C(6> bond. Only 4,7-phenanthroline gave minor products, of which one the bisadduct 167 was isolated in approximately 7% yield. Phenanthridine reacts with two nitrile oxides but affords phenanthridin-6-one rather than a cyclo-adduct (336). 

Benzo-flw-triazine tri-N-oxides 384 (R = H, Me R1 = mesityl, 2,6-ClC6H3) are formed from the reaction of nitrile oxides R CNO with benzofuroxans 385. The structure of 384 (R = Me, R1 = mesityl) has been confirmed by X-ray crystal structure analysis (431). 

Optically active 3-arylisoxazoline-5-carboxylic acid derivatives 403 or 404 have been, prepared by the reaction of (S)- or (/ )-3-acryloyl-4-benzyl-5,5-dimethyloxazolidin-2-one (405 or 406) with nitrile oxides, obtained from benzo-hydroximoyl chloride and its substituted derivatives in the presence of a catalytic amount of metal salt, for example, Yb(OTf)3 (445). This procedure improves the diastereoselectivity of compounds 403 or 404, which are industrially useful as intermediates for various drugs and agrochemicals. It also enables the amount... 

Benzofurazans are thermally more stable but can be cleaved photolytically. For example, benzo-furazan itself in benzene affords cyanoisocyanate (17) and azepine (18), the latter being formed by reaction of the solvent with the putative intermediate acylnitrene (19) (Scheme 5) further supporting evidence for the proposed pathway is provided by trapping the nitrile oxide precursor with dimethyl acetylenedicarboxylate and isolation of the methylurethane derivative of the isocyanate <75JOC2880>. Photolysis of diphenylfurazan yields benzonitrile, diphenylfuroxan and 3,5-diphenyl-1,2,4-oxadiazole. 

The same compound has been prepared in poor yield by treating benzo-nitrile oxide with dicyandiamide (J9) (see p. 826). 

Although thermally allowed, the [2 + 4] cycloaddition of thiophene with nitrile oxides leads to low yields of products, even when thiophene itself is used as solvent (77JCS(P2)706, 78T3545). The yield is improved if the dimerization of the nitrile oxide is retarded. Both mono- and bis-adducts have been isolated. The most important feature of the cycloaddition, however, is the regiospecificity (Scheme 77). In contrast, benzo[6]thiophene gave a mixture of both possible regioisomers, although not in equal amounts. 

Benzo[6]thiophene 1,1-dioxides undergo [2+4] cycloaddition with 1,3-dienes such as cyclopentadiene, anthracene, etc. (70AHC(11)177>. Cycloaddition with dipolar species such as diazoalkanes (74M550), nitrilimines (74M869) and nitrile oxides (79TL4845) have also been described (Scheme 192). 

According to Sasaki et al.,212 diphenylcyclopropenone reacts with A-iminopyridinium ylids on refluxing in benzene to produce 2,4,5-trisubstituted-6//-1,3-oxazine-6-one (69) [Eq. (54)]. Matsukubo and Kato213 described the reaction of diphenylcyclopropenone and benzo-nitrile oxide through a hypothetical spiro intermediate to give 69 (R = Ph) in 40% yield [Eq. (55)]. 

Closure of Bonds 1—7a and 3—3a Indoxazene derivatives are also accessible by 1,3-dipolar cycloaddition of nitrile oxides or nitrones to suitable dipolarophiles. Minisci and Quilico55 obtained the 3-phenyl compound by addition of benzo-nitrile oxide to benzyne [Eq. (4)]. The method is more widely applicable to the preparation of reduced indoxazenes, which will be dealt with later (Section II, D). 

Aurich and Stork have described benzo-l,2,4-oxadiazine oxyls (e.g., 276) which arise via cycloaddition of phenylhydroxylamine to nitrile oxides. (Hyperfine splittings are indicated for 276 in gauss.)... 

For instance in benzene and some of its homologs, carbazolyl-N-oxides 246 are detected, in thiophene the heteroanalog radical 247 is formed. On the other hand in furan a 1.4-addition takes place giving product radical 248. Analogously, reaction with anthracene leads to formation of 250. Furthermore reaction of 245 with benzo-nitrile oxides 6 yields benzimidazolyl-N.N -dioxides 249. 

Oxadiazoles," 1,3,4-oxadiazoles" and 1,2,5-oxadiazoles are well known, but the 1,2,3-oxadiazole system, which calculations indicate to be unstable relative to its ring-open diazo-ketone tautomer," is known only as a benzo-fused derivative (in solution) and in mesoionic substances, known as sydnones ," which have been well investigated. Furoxans ," which are formed by the dimerisation of nitrile oxides, have also been extensively studied. 1,2,3-Thiadiazoles, 1,2,4-thiadiazoles, 1,3,4-thiadiazoles" and... 

Benzo[b]thiophene 1,1-dioxide 38 and its many derivatives undergo 1,3-dipolar cycloadditions with a variety of 1,3-dipoles such as nitrile oxides (Scheme 27) [123, 127, 128], nitrones (Scheme 28) [127], and nitrile imines (Scheme 29) [129,130]. 

Additional examples of synthetic applications of hypervalent iodine-induced heterocyclizations include the following the metal-free one-pot synthesis of 2-acylbenzothiazoles by oxidative cyclization of multiform substrates [434], iodine(III)-mediated tandem oxidative cyclization for construction of 2-nitrobenzo[ ]furans [435], hypervalent iodine mediated oxidative cyclization of o-hydroxystilbenes into benzo- and naphthofu-rans [436], PhI(OCOCF3)2-mediated synthesis of 3-hydroxy-2-oxindoles and spirooxindoles from anilides [437], synthesis of isoxazoles by hypervalent iodine-induced cycloaddition of nitrile oxides to alkynes [438],... 

A one-pot synthesis ofbenzo[rf]isoxazole-4,7-diols 4 was efficiently performed in aqueous medium via 1,3-DC of nitrile oxide and benzoquinone intermediates generated by oxidation of aldoxime and phenol derivatives with iodobenzene diacetate. Such a strategy was also applied to synthesize various polynuclear isoxazole systems (13JOC8386). Benzo[isoxazole derivatives were regioselectively obtained by 1,3-DC of nitrile oxides (and nitrones) with 3-boryl- and 3-silylbenzynes (13JOC2965). 

Due to the high electrophilic nature of arynes, they are excellent dipolarophiles and can add to various 1,3-dipoles, leading to the construction of a range of benzo-fused five-membered heterocycles (Scheme 2). The commonly used 1,3-dipoles are nitrones, nitrile oxides, nitrile imines, azomethine imines, azides, diazo compoxmds, etc. Most of these reactions work under mild conditions in the absence of any transition-metal catalyst. 

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