Oxaziridines rearrangement reactions

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. 

Irradiation of the unsymmetrically substituted 2,3,4,6-tetraphenylpyridine 1-oxide (5) under these conditions gives 2,4,6,7-tetraphenyl-l, 3-oxazepine (7) in 30 % yield, together with 2,4,5,6-tetraphenylpyridin-3-ol (10) in 37% yield and 2,3,4,6-tetraphenylpyridine (30%).11 It has been suggested that the reaction proceeds by way of the oxaziridines 6 (which yields 7) and 8 (which yields the isomeric oxazepine 9) the latter rearranges to the pyridinol 10. 

En gros, the N insertion reactions can be subdivided into a Beckmann type and a Schmidt-type rearrangement part. Furthermore, some photochemical rearrangements of chiral oxaziridines are known to generate a range of optically active lactams. 

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). 

Photochemical Rearrangement Isomerization of nitrones to oxaziri-dines is a general reaction of various cyclic and acyclic nitrones (447-449). When this reaction is reversible, many transformations of nitrone to oxaziridine and back to nitrone can be carried out without decomposition. This reaction is of special interest in view of light energy accumulation (450, 451). 

Thioxo-1,2,4-dithiazolidines can be obtained from thioxo-l,2,4-thiadiazolidines by Dimroth rearrangement (Scheme 47) or reversibly by addition and elimination of acetone (Scheme 22). 1,2,4-Dithiazole type products are also obtained from thiocarbonyl isothiocyanates (154) by reaction with CI2 <84CHEC-I(6)897>, PhMgBr, Sj, or CS2. Other routes include reactions of carbonyl isothiocyanates and thiocarbonyl isocyanates with P4S10 or Sg <84Chec-I(6)897> and sulfonyl isocyanates with dialkyl thioketenes. Phenylisothiocyanate heated with N,C-disubstituted oxaziridines affords 3,5-diimino-l,2,4-dithiazolidines (226, 227). Other miscellaneous syntheses of 1,2,4-dithiazoline derivatives include cyclization of A7-thioacyl hexafluoroacetonimine to 5,5-bis(trifluoromethyl)-... 

A -Arylimincs (21a) can be oxidatively rearranged to fonnamides (21b) with sodium perborate.42 The reaction works best for secondary or aryl R groups. An oxaziridine intermediate is proposed. Results with chiral secondary R groups indicate epimeriza-tion, suggested to occur via equilibration of (21a) with its enamine tautomer. 

Considering that the present paper does not intend to analyze the chemical reactions of oxaziridines, we refer only to some publications in this field published in recent years. Certain oxaziridines undergo stereoelectronically controlled photochemical rearrangement into lactams (equation 49)204-2i9... 

They have further pointed out that the lower regioselectivity observed in the thermal rearrangement of oxaziridines does not rule out the above stereoelectronic requirement. In this case, the energy required for the reaction in sufficient to induce both nitrogen inversion in the starting oxaziridine and migration of the C-substituents. 

Other relevant described reactions, which affect the stability [72] and are related to some adverse effects of these compounds (see below) [73], have been the photochemical transformations. In fact, QDO undergoes rearrangements in the presence of UV-irradiation, passing through an oxaziridine intermediate, like an acyclic nitrone (Fig. 8). The final products depend on the QDO 2,3-substitutions and reaction conditions [72,74,75]. 

White et a/, reported that ring-closing metathesis (RCM) of oxaziridine diene 37 afforded amide 38 and cycloalk-ene 39 in 7% and 36% yields, respectively <20010L413>. Under these conditions, oxaziridine-to-amide rearrangement is promoted. On reaction of oxaziridine 40 with KMn04 in acetone in the presence of 10% H2SO4, formamide acid 41 was isolated in 30% yield <2002T9431>. 

Xanthate 169 with oxaziridine 33 gave -benzyl 0-isopropyl carbonothioate 172 and iJ-benzyl 0-isopropyl carbono(dithioperoxoate) 173 in a ratio of 93 7 <1997J(P1)2019>. The reaction is believed to go through sulfur oxidation to give sulfine intermediate 170 that rearranges to an oxathiirane 171 intermediate (Scheme 5). 

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