Benzonitrile 1,2-cycloaddition

Cycloadditions of benzonitril-4-nitrobenzylide to a variety of carbon to heteroatom multiple bonds including methyl dithiobenzoate and dimethyl trithiocarbonate (Scheme 148), X = MeS or Ph, have been examined in detail by Huisgen et al. (757). 

Dihydrofuran (376) and 2,5-dihydrofuran (377) react with nitrile oxides to give furo[2,3-6 ]isoxazoles (378) and furo[3,4-rf]isoxazoles (379), respectively, as cycloadducts. The double bonds of furan, pyrrole and thiophene also react when the nitrile oxide is generated in situ. Thus furan and benzonitrile oxide gave (380), and with 2-methyl-2-oxazoline the cycloadduct (381) was obtained (71AG(E)810). These and related cycloadditions are discussed in Chapter 4.36. 

Photolysis of 2,3-diphenyl-A -azirine (442) generates benzonitrile ylide (443). Irradiation in the presence of ethyl cyanoformate resulted in a mixture of the oxazoline (444) and the imidazole (445) by 1,3-dlpolar cycloaddition to the carbonyl and nitrile group, respectively (72HCA919). 

The reaction of benzonitrile A-oxide with a- and )3-azidostyrenes (351) and (352) gave 3,5- and 3,4-diphenylisoxazoles (353) and (354), respectively, in good yields (74JOC1221). Clearly, the X function has a pronounced directional effect on this type of 1,3-cycloaddition... 

Alkylarylisoxazoles can be obtained from the cycloaddition of nitrile Af-oxides to substituted alkynes or alkenes (Section 4.16.4.1.2(ii)), and from the condensation of the 1,4-dilithio oximes (358) with benzonitriles (72JHC183) or amides (78JOC3015). 

The cycloaddition of benzonitrile oxide to cis- and rrans-l,2-dichloroethylene produced the appropriate cis- and trans-4,5-dichloro-3-phenyl-2-isoxazoline diastereomers. Base elimination produced only one compound, 4-chloro-3-phenyloxazole (Scheme 103) (70CJC3753). 

Bravo et al. studied the reaction of various ylides with monooximes of biacetyl and benzil. Dimethylsulfonium methylide and triphenylarsonium methylide gave 2-isoxazolin-5-ol and isoxazoles, with the former being the major product. Triphenylphosphonium methylide and dimethyloxosulfonium methylide gave open-chain products (Scheme 135) (70TL3223, 72G395). The cycloaddition of benzonitrile oxide to enolic compounds produced 5-ethers which could be cleaved or dehydrated (Scheme 136) (70CJC467, 72NKK1452). 

Dihydro-l,2-benzisoxazole was prepared by the cycloaddition of benzonitrile N-oxide to 1,4-benzoquinones with subsequent oxidation of the hydroquinone (Scheme 174) (72JAP(K)7242659, 50G140). 

A variety of 1-azirines are available (40-90%) from the thermally induced extrusion (>100 °C) of triphenylphosphine oxide from oxazaphospholines (388) (or their acyclic betaine equivalents), which are accessible through 1,3-dipolar cycloaddition of nitrile oxides (389) to alkylidenephosphoranes (390) (66AG(E)1039). Frequently, the isomeric ketenimines (391) are isolated as by-products. The presence of electron withdrawing functionality in either or both of the addition components can influence the course of the reaction. For example, addition of benzonitrile oxide to the phosphorane ester (390 = C02Et) at... 

Photochemical [2 + 2] cycloaddition of benzonitrile and of 1- and 2-naphthonitriles to electron-rich alkenes such as 2,3-dimethyIbut-2-ene gives the corresponding 2-aryl-l-azetines in poor yield 72JA5929,76CC729, 77JOC4238). This does not appear to be a versatile route to 1-azetines. 

Unlike azulene, 3-phenylcyclopent[e]azepine (1) undergoes cycloaddition with diphenylacetyl-ene to give cycloadduct 2 which, under the reaction conditions, eliminates benzonitrile to give... 

Dipolar cycloaddition of benzonitrile oxide to 5-methoxy-6-methyl-6FM,4-diazepine results in a l,2,4-oxadiazolo[4,5-d][l,4]diazepine.189... 

An interpretation based on frontier molecular orbital theory of the regiochemistry of Diels Alder and 1,3-dipolar cycloaddition reactions of the triazepine 3 is available.343 2,4,6-Trimethyl-benzonitrile oxide, for example, yields initially the adduct 6.344... 

Aspects of benzonitrile oxide cycloaddition to all three parent diazines have been investigated <96T6421>, and the stereochemistry of resultant biscycloadducts determined <96JCR(S)220>. 

A dipolarophile bearing an ionic group and an associated counterion provides enhanced selectivity as has been recently demonstrated by Raposo and Wilcox [14]. Cycloaddition of benzonitrile 4 and the uncharged amine 5 a (a chiral phenylmaleimide derivative) in THE or chloroform provides a mixture of cycloadducts 6-9a in 1 4 4 4 diastereomeric ratio (i.e., 8 5 in favor of the methyl face approach of the dipolarophile. The ortho-substituents of the... 

Cycloaddition Reactions with Mesityl Azide, Diphenyldiazomethane, Isocyanides, and Benzonitrile... 

Furthermore, the Si=P bond in 15a reacts with organocyanides in a [2+2]-cycloaddition. Thus, the reaction of 15a with benzonitrile gave the phosphaazasilacyclobut-3-ene 41 (Eq. 12).14... 

The reactions of 44a,c with benzonitrile and rm-butylphosphaacetylene show that the Si=As bond easily forms [2+2]-cycloaddition products with main-group-element triple bonds.14 However, as in the case of Si=P bonds, the Si=As bond does not react with the C=C triple bond in al-kynes. 

The stannanimine [(Me3Si)2N] 2Sn=NDip(Dip = 2,6-diisopropylphe-nyl), undergoes a [2 + 3] cycloaddition with benzonitrile oxide depicted below,103 with 2,6-diethylphenyl azide, a stannatetrazole is formed.88... 

N-donor ligand. The reaction appears to proceed via an acyclic iminoplatinum(II) intermediate that undergoes a subsequent intramolecular cyclization. Some mechanistic aspects of this versatile reaction have been elucidated.225,226 A4-l,2,4-oxadiazolines have been prepared by the [2+3] cycloaddition of various nitrones to coordinated benzonitrile in m-[PtCl2( D M SO)(PhCN)] precursors.227,228 Racemic and chiral [PtCl2(PhMeSO)(PhCN)] complexes have also been used in order to introduce a degree of stereoselectivity into the reaction, resulting in the first enantioselective synthesis of A4-l,2,4-oxadiazolines, which can be liberated from the complexes by the addition of excess ethane-1,2-diamine. 

Compound 384 derived from the reaction of two molecules of benzonitrile oxide (341) with one of BCP (3). Its formation can be explained with the cycloaddition of a second molecule of 341 to the isoxazoline Ml to give the isoxazolidine M5, which undergoes a thermal rearrangement to 384 (Scheme 54). 

Benzocyclobutene, when generated by oxidation of its iron tricarbonyl complex, can function as the dipolarophile in 1,3-dipolar cycloaddition reactions with arylnitrile oxides (Scheme 113).177 Unfortunately the synthetic versatility of this type of process is limited because of the unreactivity of other 1,3-dipolar species such as phenyl azide, benzonitrile N-phenylimide, and a-(p-tolyl)benzylidenamine N-oxide.177... 

In particular, the reactions of electrophilically activated benzonitrile A-oxides with 3-methylenephthalimidines with formation of 2-isoxazolines and oximes and the cycloaddition between alkynyl metal(O) Fischer carbenes and nitrones leading to 4-isoxazolines have been investigated by density functional theory methods <06JOC9319 06JOC6178>. 

Analogously, the mesoionic jV-methyl thiazol-5-ones and l,3-dithiol-4-ones afforded A-methyl-4-pyridones and thiapyran-4-ones when reacting with diphenyl cyclopropenone and its thione261. Benzonitrile oxide apparently gives a 1,3-dipolar cycloaddition to the C=0 group of diphenyl cyclopropenone rationalizing the formation of triphenyl-l,3-oxazin-6-one 41626i ... 

Formation of mixtures of the above type, which is common with internal olefins, do not occur with many functionalized alkenes. Thus, tertiary cinnamates and cinnamides undergo cycloadditions with benzonitrile oxides to give the 5-Ph and 4-Ph regioisomers in a 25-30 75-70 ratio. This result is in contrast to that obtained when methyl cinnamate was used as the dipolarophile (177). 1,3-Dipolar cycloaddition of nitrile oxides to ethyl o -hydroxycinnamate proceeds regiose-lectively to afford the corresponding ethyl fra s-3-aryl-4,5-dihydro-5-(2-hydro-xyphenyl)-4-isoxazolecarboxylates 36 (178). Reaction of 4-[( )-(2-ethoxycarbo-nylvinyl)] coumarin with acetonitrile oxide gives 37 (R = Me) and 38 in 73% and 3% yields, respectively, while reaction of the same dipolarophile with 4-methoxy-benzonitrile oxide affords only 37 (R = 4-MeOCr>H4) (85%) (179). 

Cycloaddition of 2-alkoxy-l,3-butadienes, H2C=C(OAlk)CH=CH2, and nitrile oxides to give isoxazolines 51 proceeds with the participation of only one of the conjugated C=C bonds. With benzonitrile oxide, only the vinyl group in alkoxydienes participates in cycloaddition reactions while in the case of phenyl-glyoxylonitrile oxide both double bonds react (222). Nitrile oxides RC=NO react with iron complexed trienes 52. The reaction proceeds with good yield and diastereoselectivity ( 90/10) to give isoxazolines 53 (223). 

Cycloalkene Derivatives Cyclopropenes readily interact with nitrile oxides. Reactions of a broad series of 3,3-disubstituted cyclopropenes with 4-substituted benzonitrile, methoxycarbonyl- and cyanoformonitrile oxides (229) as well as with di(isopropoxy)phosphorylformonitrile oxide (230) give 2-oxa-3-azabicyclo[3.1.0]hexene derivatives 62. Stereoselectivity of the cycloaddition is governed by both steric and polar factors. In particular, steric factors are supposed to prevail for 3-methyl-3-phenylcyclopropene affording 62 [R1 =... 

Similarly, other cycloadducts of nitrile oxides with C6o were synthesized. The cycloadducts were characterized by 13C NMR spectroscopy and high-resolution fast atom bombardment (FAB) mass spectrometry. It should be mentioned that X-ray structure determination of the 3-(9-anthryl)-4,5-dihydroisoxazole derivative of C6o, with CS2 included in the crystals, was achieved at 173 K (255). Cycloaddition of fullerene C60 with the stable 2-(phenylsulfonyl)benzonitrile oxide was also studied (256). Fullerene formed with 2-PhSC>2C6H4CNO 1 1 and 1 2 adducts. The IR, NMR, and mass spectra of the adducts were examined. Di(isopropoxy)phosphorylformonitrile oxide gives mono- and diadducts with C60 (257). Structures of the adducts were studied using a combination of high performance liquid chromatography (HPLC), semiempirical PM3 calculations, and the dipole moments. 

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