Nitrones, synthesis oxaziridines

The photochemical synthesis of optically active oxaziridines from prochiral nitrones was driven by an interest in examining the configurational stability of the oxaziridin nitrogen atom. Nitrone 7 was irradiated at — 78°C in a 1 1 mixture of ( + )- or (— )-2,2,2-trifluorophenylethanol (8) and fhiorotrichloromethane yielding nitrone 9lent-9 in 30% ee (absolute stereochemistry unknown) [17,18]. At room temperature this selectivity decreased to 5% ee. Less bulky residues also reduced the selectivity. An exchange of f-butyl by /-propyl led to 20% ee at — 78°C (Scheme 5). 

The reported synthesis and properties of an oxaziridine by the thermal isomerization of the C7-trityl ester of 3-ac/nitrocamphor bears reinvestigation, particularly in view of the recent report that irradiation of nitronate salts yields hydrox-amic acids but that oxaziridine intermediates could not be detected.) A -Sulfonyl-oxaziridines also rearrange, thermally to nitrones that further decompose to products, but photochemically they yield amides. ... 

The synthesis of oxaziridines can be accomplished from imines, nitrones or carbonyl compounds ... 

The Oxone-acetone system has also been employed for the synthesis of simple oxaziridines fromiV-aLkylaldimines (eq 19). Interestingly, the A-phenyl analogs produce the isomeric nitrones rather than the oxaziridines (eq 20). It is noteworthy that MeCN can replace acetone as the solvent in this procedure. 

Cyclization. A new approach to the synthesis of oxaziridines involves the reaction of tosyl chloride in aqueous alkaline solution with a cyclic nitrone this reaction appears to be mechanistically similar to the cyclization of diol monotosylates in epoxide synthesis. This method has been applied to heterocyclic steroidal nitrones (276). ° Photo-oxidation of cyclohexylamine may... 

Oxaziridines easily convert to transient nitrones, which can undergo a [3 -t- 2] cycloaddition reaction in the presence of a Lewis acid catalyst. On the basis of this concept, Yoon and coworkers developed a new method for the synthesis of A-nosyl-l,2-isoxazolidines with a variety of substituents in good to excellent yields. It involves transformation of oxaziridine to nitrone and Lewis acid-assisted 1,3-cycloaddition with alkene [22]. In all reactions of styrene investigated, the cycloaddition shows high activities and diastereoselectivities. Cis- or... 

The synthesis of the protected tetrapeptide Ph-Ala-Gly-Val by rearrangement of the nitrone function to the corresponding oxaziridines has been reported. In turn oxaziridines rearrange to the amide, generally under acid catalysis. This is a significant example of the application of a well known reaction into a practical synthetic methodology. In what appears to be a seminal paper, opening new perspectives for the synthesis of polypeptides, the proof of concept of this method has been achieved, with the indication that several limitations of the present approach may be overcome. 

Larock and coworkers uncovered a facile synthesis of dihydrobenzisoxazoles by the insertion of arynes into C-O o-bond of oxaziridines. Notably, in this reaction, the bulky tertiary butyl group present on oxaziridine moiety was the key to success for the generation of dihydrobenzisoxazoles 75 with high yields (Scheme 32) [55]. This reaction was carried out in the presence of CsF, in DME at 90 °C with stoichiometric amounts of Na2C03. Mechanistically, the reaction can be considered in two ways. In pathway a, the nitrones intermediate 74 generated from 73 xmdergoes an efficient [3+2] cycloaddition reaction to afford 75. Alternatively, the insertion of arynes into the C-O o-bond of oxaziridines 73 can also furnish the desired product (pathway b). It is noteworthy that this reaction can lead to (hetero) aryl-, alkyl-, and naphthyl-substituted dihydrobenzisoxazoles. 

---