An oxaziridine is an organic molecule
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...

 that features a three-membered heterocycle
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....

 containing oxygen, nitrogen, and carbon.


Oxaziridine derivatives were first synthesized in the mid 1950s by Emmons
William D. Emmons
William D. Emmons was an American chemist and published together William S. Wadsworth a modifications to the Wittig-Horner reaction using phosphonate-stabilized carbanions now called the Horner-Wadsworth-Emmons reaction or HWE reaction or Horner-Wittig reaction-Life:Emmons studied at the...

 and subsequently by Krimm and Horner and Jürgens. Whereas oxygen and nitrogen typically act as nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

s due to their high electronegativity
Electronegativity, symbol χ , is a chemical property that describes the tendency of an atom or a functional group to attract electrons towards itself. An atom's electronegativity is affected by both its atomic number and the distance that its valence electrons reside from the charged nucleus...

, oxaziridines allow for electrophilic
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...

 transfer of both heteroatoms. This unusual reactivity is due to the presence of the highly strained three membered ring and the relatively weak N-O bond. 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
Steric effects
Steric effects arise from the fact that each atom within a molecule occupies a certain amount of space. If atoms are brought too close together, there is an associated cost in energy due to overlapping electron clouds , and this may affect the molecule's preferred shape and reactivity.-Steric...

. The unusual electronics of the oxaziridine system may be exploited to perform a number of oxygen and nitrogen transfer reactions including, but not limited to: α-hydroxylation of enolates, epoxidation
An epoxide is a cyclic ether with three ring atoms. This ring approximately defines an equilateral triangle, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in...

 of alkenes, selective oxidation of sulfide
A sulfide is an anion of sulfur in its lowest oxidation state of 2-. Sulfide is also a slightly archaic term for thioethers, a common type of organosulfur compound that are well known for their bad odors.- Properties :...

s and selenide
A selenide is a chemical compound in which selenium serves as an anion with oxidation number of −2 , much as sulfur does in a sulfide. The chemistry of the selenides and sulfides are similar....

s, amination
Amination is the process by which an amine group is introduced into an organic molecule. Enzymes which catalyse this reaction, are termed aminases. This can occur in a number of ways including reaction with ammonia or another amine such as an alkylation, reductive amination and the Mannich reaction...

 of N-nucleophiles and N-acylamidation.

Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 oxaziridine reagents have been developed, which allow for stereospecific
In chemistry, stereospecificity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one of the stereoisomers."Overlap Control of Carbanionoid Reactions. I. Stereoselectivity in Alkaline...

 transfer of heteroatoms. Chirality in oxaziridine compounds may be derived from the structure of the substituents on the oxaziridine, or from the conformationally locked nitrogen atom. Oxaziridines are unique in their exceptionally high inversion barrier for nitrogen to retain its stereochemical configuration. Chiral camphorsulfonyloxaxiridines were synthesized by F. A. Davis in the 1970s have become a cornerstone of asymmetric synthesis. Among many prominent total syntheses employing oxaziridines, both the Holton Taxol total synthesis
Holton Taxol total synthesis
The Holton Taxol total synthesis, published by Robert A. Holton and his group at Florida State University in 1994 was the first total synthesis of Taxol ....

 and the Wender Taxol total synthesis
Wender Taxol total synthesis
The Wender Taxol total synthesis in organic chemistry describes a Taxol total synthesis by the group of Paul A. Wender at Stanford University published in 1997. This synthesis has much in common with the Holton Taxol total synthesis in that it is a linear synthesis starting from a naturally...

 feature asymmetric α-hydroxylation with camphorsulfonyloxaxiridine as a key step in the synthesis of Taxol, a complicated natural product marketed as a chemotherapy agent.

N-H, N-Alkyl, N-Aryloxaziridines

The two main approaches to synthesis of N-H, N-Alkyl, and N-Aryloxaziridines are oxidation of imine
An imine is a functional group or chemical compound containing a carbon–nitrogen double bond, with the nitrogen attached to a hydrogen atom or an organic group. If this group is not a hydrogen atom, then the compound is known as a Schiff base...

s with peracids
Peroxy acid
A peroxy acid is an acid which contains an acidic -OOH group. The two main classes are those derived from conventional mineral acids, especially sulfuric acid, and the organic derivatives of carboxylic acids...

 (A) and amination of carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....

s (B).
Additionally, oxidation of chiral imines and oxidation of imines with chiral peracids may yield enantiopure oxaziridines. Some oxaziridines have the unique property of configurationally stable nitrogen atoms at room temperature due to an inversion barrier of 24 to 31 kcal/mol. Enantiopure oxaziridines where stereochemistry is entirely due to configurationally stable nitrogen are reported.


In the late 1970s and early 1980s F. A. Davis synthesized the first N-Sulfonyloxaziridines, which act exclusively as oxygen transfer reagents, and are the most predominantly used class of oxaziridines today. While originally synthesized with mCPBA
Meta-Chloroperoxybenzoic acid
meta-Chloroperoxybenzoic acid is a peroxycarboxylic acid used widely as an oxidant in organic synthesis. mCPBA is often preferred to other peroxy acids because of its relative ease of handling...

 and the phase transfer catalyst benzyltrimethylammonium chloride, an improved synthesis using oxone as the oxidant is now most prevelent.

There are many N-sulfonyloxaziridines used today, each with slightly different properties and reactivity. A summary of some of these reagents may be found in the table below.

Perfluorinated oxaziridines

Perfluorinated oxaziridines display an interesting reactivity scheme unique from hydrocarbon
In organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons from which one hydrogen atom has been removed are functional groups, called hydrocarbyls....

 based oxaziridines. The highly electron withdrawing perfluoroalkyl substituents cause oxaziridines of this class to have reactivity more similar to dioxirane
A dioxirane is a molecule containing a three-membered ring composed of one carbon and two oxygens. Somewhat unstable, they are used in organic synthesis as oxidizing reagents. The only dioxirane in common use is dimethyldioxirane , the oxirane derived from acetone....

s than typical oxaziridines. Notably, perfluoroalkyloxaziridines have the ability to 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.

α-Hydroxylation of enolates

α-hydroxyketones, or acyloin
Acyloins are a class of organic compounds in organic chemistry sharing a common functional group consisting of a hydroxyl group placed on the α-position of a carbonyl group.- Nomenclature :Common types of ketols include:...

s, are an important synthetic motif present in many natural products. α-hydroxyketones have been synthesized in many ways, including reduction of α-diketones, substitution of a hydroxyl for a leaving group and direct oxidation of an enolate. Oxodiperoxymolybdenum(pyridine)-(hexamethylphosphoric triamide) (MoOPH) and N-sulfonyloxaziridines are the most common electrophilic sources of oxygen implemented in this process. One advantage of using N-sulfonyloxaziridines is that higher chiral induction is almost invariably observed relative to MoOPH and other oxidants. High yield (77-91%) and dr (95:5 - 99:1) are reported for α-hydroxylation with the Evans' chiral auxiliary with N-sulfonyloxaziridine as the electrophile. Chiral induction has been demonstrated with many other chiral ketones and ketones with chiral auxiliaries
Chiral auxiliary
A chiral auxiliary is a chemical compound or unit that is temporarily incorporated into an organic synthesis so that it can be carried out asymmetrically with the selective formation of one of two enantiomers...

, including SAMP and RAMP.
Davis has performed extensive work on asymmetric hydroxylation of prochiral enolates with camphorsulfonyloxaziridine derivatives, achieving moderate to high enantiomeric excess
Enantiomeric excess
The enantiomeric excess of a substance is a measure of how pure it is. In this case, the impurity is the undesired enantiomer .-Definition:...

. The commonly accepted proposed transition state that justifies this stereochemical outcome involves an open transition state where the steric bulk of R1 determines the face of approach.
Interestingly, the selectivity of some hydroxylations may be drastically improved in some cases with the addition of coordinating groups alpha to the oxaziridine ring as oxaxiridines 3b and 3c in the table above. In these instances it is proposed that the reaction proceeds through a closed transition state where the metal oxyanion is stabilized by chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....

 from the sulfate and coordinating groups on the camphor skeleton.
α-Hydroxylation with oxaziridines has been widely implemented in total synthesis. It is a key step in both the Holton Taxol total synthesis
Holton Taxol total synthesis
The Holton Taxol total synthesis, published by Robert A. Holton and his group at Florida State University in 1994 was the first total synthesis of Taxol ....

 and the Wender Taxol total synthesis
Wender Taxol total synthesis
The Wender Taxol total synthesis in organic chemistry describes a Taxol total synthesis by the group of Paul A. Wender at Stanford University published in 1997. This synthesis has much in common with the Holton Taxol total synthesis in that it is a linear synthesis starting from a naturally...

. 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
Okadaic acid
Okadaic acid is a toxin that accumulates in bivalves and causes diarrheal shellfish poisoning. The molecular formula of okadaic acid, which is a derivative of a C38 fatty acid, is C44H68O13.-History:...


Epoxidation of alkenes

Epoxidation of alkenes is a versatile synthetic technique in organic synthesis. Epoxides may be derivatized to a number of useful functional groups and motifs. Classically, epoxidation is carried out with mCPBA or other peracids. Oxaziridines have been found to perform similar chemistry, and are useful for the formation of highly acid sensitive epoxides. Papeo et al. performed a synthesis of (-)-Chaetominine that utilized oxaziridine epoxidation as a late stage transformation as seen below.
Another transformation of high synthetic utility is asymmetric epoxidation. There exist a number of asymmetric epoxidations in the literature, including the Sharpless epoxidation
Sharpless epoxidation
The Sharpless Epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols....

, the Jacobsen-Katsuki epoxidation
Jacobsen epoxidation
The Jacobsen Epoxidation, sometimes also referred to as Jacobsen-Katsuki Epoxidation is a chemical reaction which allows enantioselective epoxidation of unfunctionalized alkyl- and aryl- substituted olefins. It is complementary to the Sharpless epoxidation...

 and the Juliá-Colonna Epoxidation
Juliá-Colonna epoxidation
The Juliá-Colonna epoxidation is an asymmetric poly-leucine catalyzed nucleophilic epoxidation of electron deficient olefins in a triphasic system...

. These methods have one major drawback in that they require very specific functionality in order to achieve selectivity. The Sharpless epoxidation is specific to allylic alcohols, the Jacobsen epoxidation requires cis-disubstituted aryl alkenes, and the Juliá epoxidation requires α-β unsaturated ketones
An enone is an unsaturated chemical compound or functional group consisting of a conjugated system of an alkene and a ketone. The simplest enone is methyl vinyl ketone or CH2=CHCOCH3....

. Epoxidation with asymmetric oxaziridine reagents is among a select few transformations that are stereospecific to unfunctionalized alkenes with sufficient asymmetric induction
Asymmetric induction
Asymmetric induction in stereochemistry describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment...

 to provide steric differentiation between faces. It has even been shown to be possible to produce stereospecific epoxidation catalytic in the oxaziridine chiral unit. Further investigation into these reactions may be required before levels of enantiometic excess become practical for large scale synthesis. Lusinichi et al. have investigated asymmetric epoxidation with a chiral oxaziridinium salt using oxone as the stoichiometric oxidant seen below.

Hydroxylation of unactivated hydrocarbons

Perfluorinated oxaziridines are known to hydroxylate unactivated hydrocarbons with remarkable regio, and diastereospecificity. This is a highly coveted transformation, and similar reactivity and specificity is seldom rivaled, especially considering the nonmetallic nature of the oxidant. Perfluorinated oxaziridines show high selectivity toward tertiary hydrogens. Hydroxylation of primary carbons and dihydroxylation of a compound with two oxidizable sites have never been observed. Retention of stereochemistry is very high, often 95 - 98%. (retenton of stereochemistry may be further enhanced by the addition of a fluoride salt).

Nitrogen transfer

Considerably less attention has been given to oxaziridines as nitrogen transfer reagents. Oxaziridines with unsubstituted or acylated nitrogens are capable of performing this chemistry. The first instance of nitrogen transfer was recorded in 1964 by Ohme and Schmitz.

Amination of N-nucleophiles

Amination of nucleophiles with N-unsubstituted oxaziridines is quite versatile in the breadth of possible nucleophiles and corresponding products. Hydrazine
Hydrazine is an inorganic compound with the formula N2H4. It is a colourless flammable liquid with an ammonia-like odor. Hydrazine is highly toxic and dangerously unstable unless handled in solution. Approximately 260,000 tons are manufactured annually...

s may be derived from the amination of secondary or tertiary amines, hydroxylamine and thiohydroxamines may be formed from their corresponding alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

s and thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...

s, sulfimides may be formed from thioether
A thioether is a functional group in organosulfur chemistry with the connectivity C-S-C as shown on right. Like many other sulfur-containing compounds, volatile thioethers have foul odors. A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen...

s and α-aminoketones may be formed by attack of corresponding enolates.


The transfer of acylated amines is more difficult than that of unsubstituted amines, although, unlike amine transfer by oxaziridines, there are no alternative methods that directly transfer acylated amines. Acylamine transfer has primarily been performed using amines and hydrazines as nucleophiles. Very few transfers of acylated nitrogens to carbon nucleophiles have been successfully performed, although some do exist in the literature.


Oxaziridines have been found to undergo rearrangement reactions via a radical mechanism
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...

 when irradiated with UV light or in the presence of a single elctron transfer reagent such as CuI. spirocylic
Spiro compound
A spiro compound is a bicyclic organic compound with rings connected through just one atom. The rings can be different in nature or identical. The connecting atom is also called the spiroatom, most often a quaternary carbon...

 oxaziridines undergo ring expansions to the corresponding lactam
A lactam is a cyclic amide. Prefixes indicate how many carbon atoms are present in the ring: β-lactam , γ-lactam , δ-lactam...

. Interestingly, 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
Thermodynamics is a physical science that studies the effects on material bodies, and on radiation in regions of space, of transfer of heat and of work done on or by the bodies or radiation...

 unfavorable product is observed exclusively, while in the reaction on the right the product derived from the less stable radical intermediate is favored.
Aubé takes advantage of this rearrangement as the key step in his synthesis of (+)-yohimbine
Yohimbine is an alkaloid with stimulant and aphrodisiac effects found naturally in Pausinystalia yohimbe . It is also found naturally in Rauwolfia serpentina , Alchornea floribunda , along with several other active alkaloids...

, a natural medicine classified by the NIH
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

 as possibly effective in the treatment of erectile dysfunction
Erectile dysfunction
Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....

 and the sexual problems caused by selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

It is also notable that oxaziridines will thermally rearrange to nitrone
A nitrone is the N-oxide of an imine and a functional group in organic chemistry. The general structure is R1R2C=NR3+O- where R3 is different from H.A nitrone is 1,3-dipole in 1,3-dipolar cycloadditions...

s. 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.

Cycloaddions with heterocumulenes

Oxaziridines undergo cycloaddition
A cycloaddition is a pericyclic chemical reaction, in which "two or more unsaturated molecules combine with the formation of a cyclic adduct in which there is a net reduction of the bond multiplicity." The resulting reaction is a cyclization reaction.Cycloadditions are usually described by the...

 reactions with heterocumulene
A cumulene is a chemical compound with two or more cumulative double bonds, for example butatriene , H2C=C=C=CH2. Unlike alkanes and most alkenes, cumulenes tend to be rigid, which makes them appealing for molecular nanotechnology. Polyynes are another kind of rigid carbon chains...

s to afford a number of unique five membered heterocycles, as depicted in the figure below. This reactivity is due to the strained three membered ring and weak N-O bond.
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