Oxaziridine

Oxaziridine derivatives were first reported in the mid-1950s by Emmons and subsequently by Krimm and Horner and Jürgens. All noted that oxaziridine underwent unusual reactions, with both nitrogen and oxygen acting contrary to their usual polarity. The peroxide process for the industrial production of hydrazine through the oxidation of ammonia with hydrogen peroxide in the presence of ketones was developed in the early 1970s. In the late 1970s and early 1980s Franklin A. Davis synthesized the first N-sulfonyloxaziridines, which act exclusively as oxygen transfer reagents, and are the most predominantly used class of oxaziridines today. Chiral camphorsulfonyloxaziridines proved useful in the syntheses of complex products, such as taxol which is marketed as a chemotherapy agent. Both the Holton Taxol total synthesis and the Wender Taxol total synthesis feature asymmetric α-hydroxylation with camphorsulfonyloxaziridine. Additionally, Forsyth implemented the transformation in his synthesis of the C3-C14 (substituted 1,7-Dioxaspiro[5.5]undec-3-ene) System of okadaic acid. == Structure and reactivity ==

Whereas oxygen and nitrogen typically act as nucleophiles due to their high electronegativity, oxaziridines allow for electrophilic transfer of either heteroatom. The unusual reactivity occurs because the central three-membered ring has high strain, producing a relatively weak N-O bond. Some oxaziridines inhibit nitrogen inversion at room temperature, with an energy barrier of 100 to 130 kJ/mol. Enantiopure oxaziridines where stereochemistry is entirely due to configurationally stable nitrogen are reported. Nucleophiles tend to attack at the aziridine nitrogen when the nitrogen substituent is small (R1= H), and at the oxygen atom when the nitrogen substituent has greater steric bulk. Hydrazine production Oxaziridines are intermediates in the peroxide process for hydrazine. Many millions of kilograms of hydrazine are produced annually by this method that involves a step wherein ammonia is oxidized in the presence of methyl ethyl ketone to give the oxaziridine: :Me(Et)C=O + NH3 + H2O2 → Me(Et)CONH + 2H2O In subsequent steps the oxaziridine is converted to the hydrazone, which is the immediate in the way to hydrazine: :Me(Et)CONH + NH3 → Me(Et)C=NNH2 + H2O Oxygen transfer α-Hydroxylation of enolates N-sulfonyloxaziridines oxidize enolates to acyloins with high chiral induction, better than (e.g.) MoOPH. Chiral induction has been demonstrated with many chiral auxiliaries, including SAMP and RAMP; Further investigation into these reactions may be required before levels of enantiometic excess become practical for large scale synthesis. Oxaziridines can also form highly acid-sensitive epoxides, Hydroxylation of unactivated hydrocarbons Perfluorinated oxaziridines hydroxylate unactivated hydrocarbons with remarkable regio- and diastereospecificity. Nitrogen transfer Oxaziridines with unsubstituted or acylated nitrogens are capable of nitrogen atom transfer, although this reactivity has received considerably less attention. Amination of N-nucleophiles Hydrazines may be derived from the amination of secondary or tertiary amines, hydroxylamine and thiohydroxamines may be formed from their corresponding alcohols and thiols, sulfimides may be formed from thioethers and α-aminoketones may be formed by attack of corresponding enolates. N-acylamidation The transfer of acylated amines is more difficult than that of unsubstituted amines. Unlike amine transfer by oxaziridines, there are no alternative methods that directly transfer acylated amines. The migrating substituent is determined by a stereoelectronic effect where the group trans to the lone pair on the nitrogen will always be the predominant migration product. In light of this effect, it is possible to take advantage of the chiral nitrogen due to high inversion barrier to direct the rearrangement. This phenomenon is demonstrated by observed selectivities in the rearrangements below. In the rearrangement on the left the thermodynamically unfavorable product is observed exclusively, while in the reaction on the right the product derived from the less stable radical intermediate is favored. It is also notable that oxaziridines will thermally rearrange to nitrones. Cis-trans selectivity of the resulting nitrone is poor, however, yields are good to excellent. It is thought that some oxaziridines racemize over time through a nitrone intermediate. Cycloadditions with heterocumulenes Oxaziridines undergo cycloaddition reactions with heterocumulenes to afford a number of unique five membered heterocycles, as shown in the figure below. This reactivity is due to the strained three membered ring and weak N-O bond. ==Synthesis==

N-H, N-alkyl, N-aryloxaziridines The two main syntheses of N-H, N-alkyl, and N-aryloxaziridines are imine oxidation with peracids (A) and carbonyl amination (B). Oxidation of chiral imines and oxidation of imines with chiral peracids may yield enantiopure oxaziridines. While originally synthesized with mCPBA and the phase transfer catalyst benzyltrimethylammonium chloride, an improved synthesis using oxone as the oxidant is now most prevalent. Perfluorinated oxaziridines With highly electron withdrawing perfluoroalkyl substituents, oxaziridines react more similarly to dioxiranes . Notably, perfluoroalkyloxaziridines hydroxylate certain C-H bonds with high selectivity. Perfluorinated oxaziridines may be synthesized by subjecting a perfluorinated imine to perfluoromethyl fluorocarbonyl peroxide and a metal fluoride to act as an HF scavenger. ==References==