page:  = <unk> = 
   
   An <unk> is an organic molecule that features a three @-@ membered <unk> containing oxygen , nitrogen , and carbon . In their largest application , <unk> are intermediates in the industrial production of hydrazine . <unk> derivatives are also used as specialized reagents in organic chemistry for a variety of oxidations , including alpha hydroxylation of <unk> , epoxidation and <unk> of olefins , and other heteroatom transfer reactions . <unk> also serve as precursors to amides and participate in [ 3 + 2 ] cycloadditions with various <unk> to form substituted five @-@ membered <unk> . Chiral <unk> derivatives effect asymmetric oxygen transfer to <unk> <unk> as well as other substrates . Some <unk> also have the property of a high barrier to inversion of the nitrogen , allowing for the possibility of chirality at the nitrogen center . 
   
   = = History = = 
   
   <unk> derivatives were first reported in the mid @-@ 1950s by Emmons and subsequently by <unk> and Horner and Jürgens . Whereas oxygen and nitrogen typically act as nucleophiles due to their high electronegativity , <unk> allow for electrophilic 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 . <unk> tend to attack at the <unk> nitrogen when the nitrogen substituent is small ( R1 = H ) , and at the oxygen atom when the nitrogen substituent has greater steric bulk . The unusual electronics of the <unk> system may be exploited to perform a number of oxygen and nitrogen transfer reactions including , but not limited to : α @-@ hydroxylation of <unk> , epoxidation of alkenes , selective oxidation of sulfides and selenides , amination of N @-@ nucleophiles and N @-@ <unk> . 
   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 . 
   Chiral <unk> proved useful in the syntheses of complex natural product , 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 <unk> . 
   
   = = Synthesis = = 
   
   
   = = = N @-@ H , N @-@ <unk> , N @-@ <unk> = = = 
   
   The two main approaches to synthesis of N @-@ H , N @-@ alkyl , and N @-@ <unk> are oxidation of <unk> with <unk> ( A ) and amination of carbonyls ( B ) . 
   Additionally , oxidation of chiral <unk> and oxidation of <unk> with chiral <unk> may yield <unk> <unk> . Some <unk> have the unique property of <unk> stable nitrogen atoms at room temperature due to an inversion barrier of 24 to 31 kcal / mol . <unk> <unk> where stereochemistry is entirely due to <unk> stable nitrogen are reported . 
   
   = = = N @-@ <unk> = = = 
   
   In the late 1970s and early 1980s Franklin A. Davis synthesized the first N @-@ <unk> , which act exclusively as oxygen transfer reagents , and are the most predominantly used class of <unk> today . While originally synthesized with <unk> and the phase transfer catalyst <unk> chloride , an improved synthesis using <unk> as the oxidant is now most prevalent . 
   Many N @-@ <unk> are used today , each with slightly different properties and reactivity . These reagents are summarized in the table below . 
   
   = = = <unk> <unk> = = = 
   
   With highly electron withdrawing <unk> substituents , <unk> exhibit reactivity more similar to that of <unk> than typical <unk> . Notably , <unk> <unk> certain C @-@ H bonds with high selectivity . <unk> <unk> may be synthesized by subjecting a perfluorinated imine to <unk> <unk> peroxide and a metal fluoride to act as an HF scavenger . 
   
   = = Reactions of <unk> = = 
   
   
   = = = <unk> production = = = 
   
   <unk> are intermediates in the Peroxide process for the production of 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 <unk> : 
   Me ( Et ) C = O + NH3 + H2O2 → Me ( Et ) <unk> + H2O 
   In subsequent steps the <unk> is converted to the <unk> , which is the immediate en route to hydrazine : 
   Me ( Et ) <unk> + NH3 → Me ( Et ) C = <unk> + H2O 
   
   = = = Oxygen transfer = = = 
   
   
   = = = = α @-@ <unk> of <unk> = = = = 
   
   α @-@ <unk> , or <unk> , are an important synthetic motifs present in many natural <unk> α @-@ <unk> have been synthesized in many ways , including reduction of α @-@ <unk> , substitution of a hydroxyl for a leaving group and direct oxidation of an <unk> . <unk> ( pyridine ) - ( <unk> <unk> ) ( <unk> ) and N @-@ <unk> are the most common electrophilic sources of oxygen implemented in this process . One advantage of using N @-@ <unk> is that higher chiral induction is almost invariably observed relative to <unk> 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 @-@ <unk> as the <unk> . Chiral induction has been demonstrated with many other chiral ketones and ketones with chiral auxiliaries , including <unk> and <unk> . 
   Extensive work has been reported on asymmetric hydroxylation of <unk> <unk> with <unk> derivatives , achieving moderate to high enantiomeric excess . The commonly accepted proposed transition state that justifies this <unk> outcome involves an open transition state where the steric bulk of R1 determines the face of approach . 
   The selectivity of some <unk> may be drastically improved in some cases with the addition of coordinating groups alpha to the <unk> ring as <unk> 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 from the sulfate and coordinating groups on the camphor skeleton . 
   α @-@ <unk> with <unk> has been widely implemented in total synthesis . It is a key step in both the Holton Taxol total synthesis and the Wender Taxol total synthesis . Additionally , Forsyth implemented the transformation in his synthesis of the C3 @-@ C14 ( Substituted 1 @,@ 7 @-@ <unk> [ 5 @.@ 5 ] <unk> @-@ 3 @-@ ene ) System of <unk> acid . 
   
   = = = = <unk> of alkenes = = = = 
   
   <unk> of alkenes is a common reaction because epoxides can be <unk> in a number of useful ways . Classically , laboratory epoxidation is carried out with <unk> or other <unk> . <unk> have been found to be useful for the formation of highly acid sensitive epoxides . ( − ) <unk> was synthesized via <unk> epoxidation as a late stage transformation as seen below . 
   Another transformation of high synthetic utility is asymmetric epoxidation . A number of asymmetric <unk> exist : the Sharpless epoxidation , the Jacobsen @-@ <unk> epoxidation , and the Juliá @-@ Colonna <unk> . These methods require specific functionality in order to achieve selectivity . The Sharpless epoxidation is specific to <unk> alcohols , the Jacobsen epoxidation requires cis @-@ disubstituted aryl alkenes , and the Juliá epoxidation requires α @-@ β unsaturated ketones . Chiral <unk> act <unk> on many <unk> alkenes . It has even possible to effect <unk> epoxidation catalytically in the <unk> chiral unit . Further investigation into these reactions may be required before levels of <unk> excess become practical for large scale synthesis . <unk> et al. have investigated asymmetric epoxidation with a chiral <unk> salt using <unk> as the stoichiometric oxidant seen below . 
   
   = = = = <unk> of unactivated hydrocarbons = = = = 
   
   <unk> <unk> are known to <unk> unactivated hydrocarbons with remarkable regio , and <unk> . This is a highly coveted transformation , and similar reactivity and specificity is seldom rivaled , especially considering the nonmetallic nature of the oxidant . <unk> <unk> show high selectivity toward tertiary hydrogens . <unk> of primary carbons and <unk> of a compound with two <unk> sites have never been observed . Retention of stereochemistry is very high , often 95 - 98 % . ( <unk> of stereochemistry may be further enhanced by the addition of a fluoride salt ) . 
   
   = = = Nitrogen transfer = = = 
   
   <unk> with unsubstituted or acylated nitrogens are capable of nitrogen atom transfer , although this reactivity has received considerably less attention . 
   
   = = = = <unk> of N @-@ nucleophiles = = = = 
   
   <unk> of nucleophiles with N @-@ unsubstituted <unk> is quite versatile in the breadth of possible nucleophiles and corresponding products . <unk> may be derived from the amination of secondary or tertiary amines , <unk> and <unk> may be formed from their corresponding alcohols and thiols , <unk> may be formed from thioethers and α @-@ <unk> may be formed by attack of corresponding <unk> . 
   
   = = = = N @-@ <unk> = = = = 
   
   The transfer of acylated amines is more difficult than that of unsubstituted amines , although , unlike amine transfer by <unk> , there are no alternative methods that directly transfer acylated amines . <unk> transfer has primarily been performed using amines and <unk> as nucleophiles . Very few transfers of acylated nitrogens to carbon nucleophiles have been successfully performed , although some do exist in the literature . 
   
   = = = <unk> = = = 
   
   <unk> have been found to undergo rearrangement reactions via a radical mechanism when irradiated with UV light or in the presence of a single electron transfer reagent such as <unk> <unk> <unk> undergo ring expansions to the corresponding lactam . Interestingly , the migrating substituent is determined by a <unk> 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 <unk> 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 . 
   <unk> takes advantage of this rearrangement as the key step in his synthesis of ( + ) <unk> , a natural medicine classified by the NIH as possibly effective in the treatment of erectile dysfunction and the sexual problems caused by selective serotonin reuptake inhibitors . 
   It is also notable that <unk> will thermally rearrange to <unk> . Cis @-@ trans selectivity of the resulting <unk> is poor , however , yields are good to excellent . It is thought that some <unk> <unk> over time through a <unk> intermediate . 
   
   = = = <unk> with <unk> = = = 
   
   <unk> undergo <unk> reactions with <unk> to afford a number of unique five membered <unk> , as depicted in the figure below . This reactivity is due to the strained three membered ring and weak N @-@ O bond . 
   
   