Oxaziridines, 2-acyl

In the oxaziridines (1) ring positions 1, 2 and 3 are attributed to oxygen, nitrogen and carbon respectively. The latter almost always is in the oxidation state of a carbonyl compound and only in rare cases that of a carboxylic acid. Oxaziridinones are not known. The nitrogen can be substituted by aryl, alkyl, H or acyl the substituent causes large differences in chemical behavior. Fused derivatives (4), accessible from cyclic starting materials (Section 5.08.4.1), do not differ from monocyclic oxaziridines. 

An investigation of acylaziridines was carried out by comparison of IR, NMR and MS data and included some 1,2-dibenzoylaziridines as well as 2-p-nitrobenzoyl-3-phenyl-oxaziridine (68IZV1530). Amide conjugation in acylated nitrogen-containing three-membered rings is weaker than in open chain acid amides. 

V-Acylation of oxaziridine (54) is of more importance, yielding 2-acyloxaziridines which were unaccessible otherwise until recently. Oxaziridines (54) derived from cyclohexanone, butanone or benzaldehyde are acylated readily by acetic anhydride, acid chlorides or isocyanates. Oxaziridines from aliphatic aldehydes, too unstable to be isolated, may be trapped in situ by benzoylation (67CB2593). 

Oxaziridines are powerful oxidizing agents. Free halogen is formed from hydrobromic acid (B-67MI50800). Reduction by iodide in acidic media generally yields a carbonyl compound, an amine and two equivalents of iodine from an oxaziridine (1). With 2-alkyl-, 2-acyl and with N-unsubstituted oxaziridines the reaction proceeds practically quantitatively and has been used in characterization. Owing to fast competing reactions, iodide reduction of 2-aryloxaziridines does not proceed quantitatively but may serve as a hint to their presence. 

Ring enlargement of A-acyl compounds, generally observed with oxaziridines, is observed only occasionally with diaziridines. Under more forced conditions of acylation with acetic anhydride, oxadiazolines like (139) were obtained (76MIP50800). A 4-nitrobenzoyl derivative rearranged at room temperature (76JOC3229). 

Oxaziridines unsubstituted at nitrogen as well as some iV-acylated oxaziridines offer synthetic potentialities due to their ability to transfer their nitrogen function to nucleophiles (Section 5.08.3.1.4). The simplicity of preparation of some aziridines from alkenes and the Spiro oxaziridine (S2) equals the simplicity of epoxidation. Aziridine (299), for example, is obtained by simple heating of indene with (52) in toluene (74KGS1629). 

Evans succeeded in oxidizing A-acyl oxazolidinone enolate 143 or 145 using oxaziridine 141 as the oxidant (Scheme 4-55).110 Representative results are summarized in Table 4-19. 

N-Acetyl derivatives of 3-phenyloxaziridine can also transfer their nitrogen function to nucleophiles. 2-(4 -Nitrobenzoyl)-3-phenyloxaziridine (69) converts piperidine to the acyl-hydrazine (101) in 92% yield within some minutes at room temperature (67JPR(36)86). Since (69) is stable in the absence of a nucleophile a nitrene is not involved in the reaction, which is assumed to occur by nucleophilic attack of the amine on the oxaziridine nitrogen. 

Nucleophiles react with /V-H and Al-acyl oxaziridines with transfer of NH and /V-acyl, respectively. Much of this chemistry (91S327) has been carried out with cyclohexanespiro-3 -oxaziridine (26) attack at the NH group gives intermediate (27) which gives cyclohexanone and animation of the nucleophile. Transfers of NH to N-, 0-, S-, and C-nucleophiles, enable the syntheses of hydrazines, /V-amino-peptides, hydroxyamines, sulfenamides, thiooximes, sulfonamides, aziridines, and a-amino acids. 

A variety of different sources of radicals have been used in several heteroaromatic substitution reactions [2] these include acyl peroxides, oxaziridines, thiohydroxa-mic Barton esters, the Gif reaction, alkyl xanthates, and ketones/H202 (Scheme 8). 

Another substrate class, for which the outcomes of a radical and a carbocationic process are opposite, are indoles (Fig. 85) [418], Indeed, when oxaziridines 315a or 315c were treated with indoles 314c in the presence of 2 or 10 mol% of C11CI2/ TBAC oxazolidinoindolines 316c were obtained as the exclusive products in 53-90% yield. The reaction is applicable to 2-, 3-, and 2,3-disubstituted indoles. Chiral indole derivatives acylated with (S)-proline units at nitrogen underwent asymmetric diastereoselective aminohydroxylation reactions with 86-91% de. Tricyclic hemiaminals derived from tryptamine derivatives could be transformed to pyrrolidinoindolines, which are core structures of a number of alkaloids. 

Treatment of NH-oxaziridine 50 withp-nitrobenzoyl chloride 51 in methylene chloride in the presence of DMAP at room temperature resulted in dihydrodioxazoles 53 and 54 in 63% yield as a 1 1 mixture of diastereoisomers <2000JOC4204>. iV-Acyl oxaziridine 52 was believed to have been formed first which rearranged to products 53 and 54. 

Zong eta/, reported a new method for preparing A -acyloxaziridines 359 via the tandem 0,N-addition of hydroxamic acids 357 to methyl propiolate 358 (Equation 14) <1998TL6227>. The reaction was carried out in the presence of a catalytic amount of A -methyl morpholine. The desired A -acyl oxaziridines were obtained in good to excellent yields (Table 32). 

In what appears to be a related reaction, benzimidazole Af-oxides give rise to ben-zimidazolinones as by-products when treated with an acyl halide in the presence of alkali. With tosyl chloride the sole product is the benzimidazolinone (111) which may be formed as in Scheme 50. The N rearrangement could also take place via the oxaziridine (112) <73JCS(P 1)705). 

Oxaziridines with no substituent on the ring nitrogen may be stabilized as the fV-acyl derivatives. Indeed, the presence of an acylating agent, that is, benzoyl chloride, is necessary for the trapping of such oxaziridines derived from aliphatic aldehydes (Table 2). ... 

A 3-acyl oxaziridine, a rare stable derivative of its kind, was made photochemi-cally from the isomeric nitrone to which it reverted upon standing. Further irradiation led both to rearrangement with acyl migration and to nitrene elimination (see Section IV.3).i ... 

Pyrazine Al-oxides and 2,3-dihydropyrazines also rearrange photochem-ically into imidazoles. From 2,5-disubstituted pyrazine 1-oxides (73) two products, 2-acyl(or aroyl) 4-substituted imidazole (74) and 2,4-disubstituted imidazole (75), result. " " The reaction (Scheme 16) presumably takes place through two isomeric oxaziridine derivatives. 

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