Reactivity of Oxaziridines

Reactions of oxaziridines with conservation of the three-membered ring 

There are only few reactions known introducing substituents to the H-bearing nitrogen of oxaziridines. (V-Alkylation of l-oxa-2-azaspiro[2.5]octane (3,3-pentamethylene-oxaziridine 52) with r-butyl chloride to give (53) was carried out for structure proof of (52). This reaction is of no preparative importance, since N-alkylated oxaziridines are easily obtained by ring synthesis. 

---

The addition of oxygen across the C—N double bond is a common and synthetically useful process. The product oxaziridines are of interest for theoretical reasons (largely due to the high configurational stability of the chiral nitrogen), as reagents (such as oxygen transfer moieties), and as synthetic intermediates. The stereochemical aspects of oxaziridine synthesis and reactivity have been reviewed. ... 

The formation and the oxidative properties of an oxaziridinium salt have been reported. With methyl fluorosulphonate the oxaziridine (30) led to the oxaziridinium salt (36) which was stable as a crystalline product at room temperature, but unstable in solution, giving (37), also obtained from (38) with methyl fluorosulphonate. NaBHt reduction of (36) led to (35). Peroxidic reactivity of (36) was shown by oxygen transfer from (36) to the imine (38) with formation of the nitrone (39) (Scheme 5). 

Compounds containing bivalent sulfur react rapidly with N—H and iV-methyl oxaziridines to form sulfenamides (R1—S—NH—R2), the stability of which depends on the reactivity of the substrate and the product. Ring closure and sulfenimine (R—S—N=CR2) formation via intermediate (52), are frequently observed products with thioamides and thioureas. Sulfinates (ArS02 Na+) are aminated to sulfonamides in excellent yield. These animations, explored in detail by Schmitz and co-workers with spirooxaziridine (51), have been reviewed <91S327> and only a few illustrative examples are given in Table 4. 

Secondary alcohols are oxidized to ketones with high regio- and stereoselectivity on treatment with perfluoro oxaziridine (64a) at room temperature, (Equation (11)) <92TL7245>. Yields are excellent and the reactivity of this oxaziridine is reported to be comparable to that of dioxiranes. 

The interaction of oxaziridines (84) and phenyl isothiocyanate is also rationalized in terms of the formation of iminothiaziridines (85) as the reactive intermediates (see Section II,A,3). The reaction yields carbodiimides, but produces the 1,2,4-thiadiazolidines 86 and/or 87 under mild conditions, probably by a mechanism outlined in Scheme 6. Members of series 86 are... 

The presence and the nature of a functional group at position 12 on imine derivatives of 5a,20(N)-conene (24) changed the reactivity of the imino-group towards peracids." By the action of one mole of p-nitroperbenzoic acid on some derivatives of 5o,2(XN)-conene (24) (with various substituents at position 12), the (20R)-oxaziridine (25), the(20S)-oxaziridine(26),and the nitrone (27) were obtained... 

Thiaziridines have been postulated as reactive intermediates in the photochemical rearrangement of thiazoles, isothiazoles, -and 4-aryl-l,3,2-oxathiazolium S-oxide," and in the conversion of oxaziridines into imines and elemental sulphur on treatment with thiourea, potassium thiocyanate, or potassium ethyl xanthate. Irradiation of a mixture of 7V-sulphinyl-aniline and diphenyldiazomethane gave iV-diphenylmethyleneaniline, which was probably formed by extrusion of sulphur monoxide from 2,3,3-triphenyl-thiaziridine 1-oxide formed as an intermediate. ... 

Three groups of workers have studied the reactivity of thiourea towards a -unsaturated ketonesThe notable lability in the reaction course was demonstrated by the simultaneous or alternative formation of different open-chain as well as cyclic products, thus clearly indicating the occurrence of nucleophilic attacks of both the sulphur and the nitrogen atoms of thiourea on both the carbonyl carbon and the 3-carbon atom of the a 3-unsaturated ketone. Other papers reporting on the nucleophilic activity of thioureas deal with reactions of the latter with oxirans, oxaziridines," acryloyl chloride," o 3-unsaturated acids," acetylenedicarboxylic acid esters, " ethyl thiocyanoacetate," and isocyanates. ... 

Extensive investigations of these compounds have revealed their unusual reactivity. This, undoubtedly, is related to the strained three-membered ring and a relatively weak N—O bond. A consequence of these features is the low basicity of the oxaziridine nitrogen compared to that of amines. Another remarkable property of some oxaziridines is that they possess a configurationally stable nitrogen atom at ordinary temperatures200. 

Oxaziridines show a diversity of reactivities perhaps the most synthetically useful behavior is their selective oxidizing ability. For example, fluoro-cA-2,3-dialky loxaziridines 141 function as effective reagents for the selective oxidation of ethers to carbonyl compounds (e.g., 142 - 143). This protocol was used for the oxidation of methoxy residues on various classes of steroids [95JOC2314]. 

The chiral oxaziridine is very reactive, even at low temperature, leading us to query its stability. Since we were proposing to carry out the preparation of the oxaziridine in a steel vessel, we investigated the thermal stability of the chiral oxaziridine on its own, in the presence of stainless steel and in the presence of ferric ion. The stability test was carried out in a RADEX safety calorimeter. The results are summarized in Figure 5. 

It is of importance to note that, using this method, inversion barriers may be computed for molecules which Eire too reactive or too unstable (for instance, H2N—SiH3, H2N—F, oxaziridine, CH2=N—H etc... ) or have barriers too high for experimental determinations to be performed. In addition it is possible to study the geometry (which cannot be obtained... 

---