Oxaziridine — Amide

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. 

The isomerization of oxaziridines (1) to acid amides with migration of a substituent from C to N is a general reaction and is always observed when no other reactions predominate under the relatively harsh conditions (heating to above 150 °C or photolysis). Even then one can make acid amide formation the main reaction by working at 300 °C (57JA5739) and by dilution techniques. For example, caprolactam (63) is formed in 88% yield by flash pyrolysis of oxaziridine (52) at about 300 °C, whereas decomposition of (52) at lower temperatures gives almost no (63) (77JPR274). 

Diaryloxaziridines are even less stable. With oxaziridines (66 Ar = Ph or 4-Me2NC6H4) acid amide formation at 25 °C proceeded in the course of 66 and 10 h respectively in the latter case there were equal amounts of H and aryl migration. Ethanol as solvent again accelerated the reaction, in the latter case by a factor of lO. ... 

In some cases acid amide formation was observed on attempted deprotonation at oxaziridine ring carbon. 2-r-Butyl-3-(4 -nitrophenyl)oxaziridine (67) was converted to the anion of acid amide (68) by sodium amide (69TL3887), while 2-(4 -nitrobenzoyl)-3-phenyl-oxaziridine (69) afforded the diacylimide (70) by addition of cyclohexylamine to its benzene solution at room temperature (67CB2593). 

Homolytic oxaziridine decomposition can be easily initiated by iron(II) ion in acidic media. Catalytic amounts are sufficient because chain reactions proceed. The reaction proceeds obviously in the case of 2-r-alkyloxaziridines like (56), where it yields the isomeric acid amide (111) (57JA5739). 

When )3-scission can occur in the radical, further reactions compete with acid amide formation. Thus oxaziridine (112) with iron(II) ion and acid yields stabilization products of the isopropyl radical. If a-hydrogen is present in the Af-alkyl group, radical attack on this position in (113) occurs additionally according to the pattern of liquid phase decomposition. 

There are differences in the high temperature behavior. While oxaziridines almost always isomerize to acid amides, a similar reaction of diaziridines, which should lead to amidines, has not been observed. Sensitivity towards bases, often encountered in oxaziridines, is observed only in some special substituted diaziridines. The tendency of some classes of oxaziridines to transfer the nitrogen function also lacks in the diaziridine field. On homolytic reactions of diaziridines there are only a few observations. 

Cleavage of N—N by potassium f-butoxide to give amidine (164) was observed with diaziridine (134). This is the only known analog of the generally observed acid amide formation from oxaziridines (74JPR999). 

From N-oxides of aromatic bases oxaziridines were obtained only at very low temperatures, but oxaziridines were often postulated as intermediates in the photoconversion of such N-oxides (Section 5.08.3.1.2). Isolation of the more stable photoisomers of nitrones also causes some problems due to their thermal and photochemical instability leading to acid amides, e.g. (69TL2281), or, by fragmentation, to carbonyl compounds and products of stabilization of nitrenes, e.g. from (260) (69ZN(B)477). 

Nitrones in general undergo a four-electron photocyclization to afford the corresponding oxaziridines. The process is stereospecific,47 proceeds via the excited singlet state, and is in certain instances photochemically reversible.48 Theoretical studies support this proposed pathway49 The nitrones 52, on direct irradiation, afford the oxaziridines 53, which on further irradiation are converted into the isomeric amides 54.so In contrast, triplet... 

For the first time, the primary nitrone (formaldonitrone) generation and the comparative quantum chemical analysis of its relative stability by comparison with isomers (formaldoxime, nitrosomethane and oxaziridine) has been described (357). Both, experimental and theoretical data clearly show that the formal-donitrones, formed in the course of collision by electronic transfer, can hardly be molecularly isomerized into other [C,H3,N,0] molecules. Methods of quantum chemistry and molecular dynamics have made it possible to study the reactions of nitrone rearrangement into amides through the formation of oxaziridines (358). 

Davis et al.111 developed another method for reagent-controlled asymmetric oxidation of enolates to a-hydroxy carbonyl compounds using (+)-camphor-sulfonyl oxaziridine (147) as the oxidant. This method afforded synthetically useful ee (60-95%) for most carbonyl compounds such as acyclic keto esters, amides, and a-oxo ester enolates (Table 4-20). 

The method is also successful for carboxylic esters167 and N,N-disubstituted amides,168 and can be made enantioselective by the use of a chiral oxaziridine.169 Dimethyldioxirane also oxidizes ketones (through their enolate forms) to a-hydroxy ketones.169 ... 

A transformation of this type also occurs in the photochemical rearrangement of the acyclic nitrone (177). to the amide (178) and an intermediate oxaziridine may. be, involved in the photochemical conversion149 of aryl oximes into the corresponding amides [Eq. (42)]. 

ASYMMETRIC OXIDATION OF LITHIUM ENOLATES OF ESTERS AND AMIDES USING (+)-(2R.8aS)-10-(CAMPHORYLSULFONYL)OXAZIRIDINE... 

Diarylnitrone (31) formation from N-substituted, diaromatic imines has been recognized to require the presence of NADPH/O2, and has been proposed to proceed via the intermediacy of an oxaziridine3 possibly arising from reaction of the parent imines with the putative P-450 [FeO]3+ species in analogy to the oxidation of olefins118. Ring cleavage of the oxaziridine then yields nitrone or amide (equation 10). 

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