Isoxazoles nitrile ylide

For isoxazoles the first step is the fission of the weak N—O bond to give the diradical (51) which is in equilibrium with the vinylnitrene (52). Recyclization now gives the substituted 2//-azirine (53) which via the carbonyl-stabilized nitrile ylide (54) can give the oxazole (55). In some cases the 2H-azirine, which is formed both photochemically and thermally, has been isolated in other cases it is transformed quickly into the oxazole (79AHC(2.5)U7). 

MNDO results suggest that the activation energies are similar for the gas phase thermal isomerization of isoxazole to oxazole via either a nitrile ylide or a keteneimine, through an azirine intermediate. The first step is rate limiting, which is in good agreement with experimental results (90JPO611). 

Oxazoles are the products of the rearrangement of isoxazoles and of C-acylazirines, these processes being intimately related (81MI41800, 76ACR37I, 77H(6)143). Photolysis of 3-acylazirines gives nitrile ylides which cyclize thermally to oxazoles (equation 131). Flash vacuum pyrolysis of 3,5-diphenylisoxazole yields as major products 2,5-diphenyloxazole, 1,2-diphenylazirine, 2-phenylindole and benzamide. 13C labelling experiments indicate that the first two compounds are formed as shown in Scheme 31. 

One case where an azirine intermediate is believed not to arise in the isox-azole photorearrangement has been reported by Padwa and coworkers. When 4-benzoyl-5-methyl-3-phenyl-isoxazole (158) or 4-acetyl-3,5-diphenyliso-xazole (159) was thermolyzed (230°C), a 2/f-azirine is presumably formed which subsequently opens to the nitrile ylide 160. Subsequent closure of 160 affords the isomeric oxazoles 161 and 162 in a ratio of 3 4. 

In sharp contrast to the thermal results, the photolysis of 158 affords only oxazole 161. The authors postulated that the nitrile ylide 160 is formed directly from the excited isoxazole in the conformation 160a. Ring closure occurs before rotation around the C-N bond, yielding only oxazole 161. Some recent MiNDo/3 calculations by Dewar and Turchi indicate that the CNC angle of nitrile ylides is less than 180° and that rotation about the C-N bond in 169 is indeed slow relative to ring closure. ... 

Isoxazole-oxazole photoisomerization was studied by irradiation of matrix-isolated 3,5-dimethylisoxazole (18) at 222 nm. 2-Acetyl-3-methyl-2H-azirine (20) was obtained, likely through an acetyl vinyl nitrene intermediate 19 as primary photoproduct, while upon longer time UV irradiation, two additional photoproducts were identified as acetyl nitrile ylide 21 and 2,5-dimethyloxazole (22) (13JOC10657). Analogously, 3,5-diphenylisoxazole and 2-benzoyl-3-phenyl-2f/-azirine behaved as precursors to triplet vinyl nitrene (of type 19) through laser flash photolysis (13JOC11349). Reductive heterocycle—heterocycle transformations of (2-nitrophenyl)isoxazole precursors, such as 23 and 26, afforded 4-amino quinolines of type 24, quinolin-4(lfJ)-ones 25, and 3-acylindoles 27. Che-moselective heterocyclizations were observed from 3,4-,4,5-, and 3,4-bis(2-nitrophenyl)isoxazoles (13OL2062). 

The addition of stabilized ylides, e.g. (63), to nitrile imides or oxides gave pyrazoles or isoxazoles respectively (Scheme 23), in extremely clean reactions which probably proceed by electrophilic attack of the dipole at the y-carbon of the phosphorane.66... 

Indoles have been prepared from reactions of o-aminophenylketones with reactive , or stable " arsonium ylides. Oxo-stabilized ylides reacted with 2-chloro-oximes to give trans-5-acyl-A -isoxazolines, and isoxazoles have been obtained from reactive arsonium ylides and a-isonitrosoketones, and from triphenylarsonium methylide and nitrile oxides The latter ylide reacts similarly with nitrile imines to give pyrazoles. With triphenylarsonium benzylides and benzoylylides,benzene diazonium salts give 1,3,4,6-substituted 1,4-dihydro-1,2,4,5-tetrazines in a reaction in which initial coupling of the reagents is followed by a dimerisation. ... 

A full account has appeared of the reactions of acyl azides with jS-keto-alkylidenephosphoranes. These phosphoranes with nitrile oxides gave isoxazoles (54) and the stable ylides (56) or (57), formed as shown via the quinquecovalent 1 1 adducts (55). ... 

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