Preparation of aziridines

One method widely used for the synthesis of aziridines is the addition of nitrenes to olefins. Along these lines, sulfonamides serve as convenient nitrene precursors, which can be converted 

An intriguing electrochemical aziridination is based on the selective anodic oxidation of N-aminophthalimide (136, oxidation potential +1.60 V) in the presence of olefins. Thus, trans-hex- 

4-en-3-one 137 is converted to the corresponding aziridine 138 in acetonitrile solution using a platinum electrode at a constant potential of +1.80 volts. The reaction mixture is buffered using triethylammonium acetate, since the cathodic process reduces proton to hydrogen gas. The use of platinum at the anode is critical, as graphite electrodes yielded no aziridination products 04PAC603 . 

Just as epoxides can be prepared from carbonyl compounds, aziridines can be accessed through the addition of amphophilic carbon centers onto imines, and sulfur ylides are frequently used as carbon donors in this regard. Thus, S-allyl tetrahydrothiophenium bromide 139 is smoothly deprotonated with strong base to provide an ylide which adds to a variety of N-protected imines. For the A-tosyl aldimine 140 derived from isovaleraldehyde, the corresponding vinyl aziridine 141 is formed in fair yield as a mixture of stereoisomers 04TL1589 . 

Chiral induction can also be quite effective when the locus of asynunetry is attached to the sulfur ylide itself The sutfonium salt 147 derived from Eliel s oxathiane can be used to deliver a benzylic center to tosyhmines (e.g., 148) and efficiently produces phenylaziridines with a very high degree of asymmetric induction. The method is amenable to gram-quantity synthesis, and the chiral auxihary can be easily recovered. In general, cisitrans mixtures are obtained, depending upon the steric bulk of the imine substituent 04JOC1409 . 

Olefin aziridination catalysts derived from other transition metals continue to be developed. Simple non-heme iron complexes have been reported to serve as effective 

Intramolecular copper-catalyzed aziridinations of sulfamates have been reported in yields up to 86% and up to 84% ee using (4 V,4 S)-2,2 -(propane-2,2-diyl)bis(4-/erf-buty 1-4,5-dihydro-l,3-oxazole), 43 07S1251 . 

Aziridines can be readily prepared utilizing 1,2-amino leaving groups as precursors. Traditionally an amine lone pair or an amide anion facilitates an intramolecular nucleophilic displacement to generate the aziridine ring. Utilization of enantiomerically pure 1,2-amino leaving groups renders the possibility of enantiopure aziridines via asymmetric synthesis. 

A facile phase-transfer catalysis protocol was reported for the conversion of p-hydroxy-a-amino esters into enantiomerically pure /V-tosyl aziridine-2-carboxylates 07TL6509 . Utilization of the same methodology allowed for preparation of an aziridine carboxamide in essentially quantitative yield. 

Asymmetric variants of imine reduction have also been developed towards enantiopure aziridines. Reduction of chiral /V-tert-butanesulfinyl a-halo imines afforded enantiopure aziridines in good to excellent yields 07JOC3211 . Enantioselective catalytic reduction of a-chloroimines utilizing metal-free L-valine-derived formamide 45 followed by base-mediated ring closure provided aziridines with preserved enantiopurity 07AG(I)3722 . 

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H -hydroxyandrost-5-en-3-one acetate and 4-methyl-6 -acetyI-H -hydroxyandrost-5-en-3-one acetate from 4-methylandrosta-3,5-diene-3,17-diol diacetate, 342 Preparation of aziridines... 

Although this variant often gives yields of less than 50%, it is a general method for the preparation of aziridines, especially of aziridinecarboxylic esters such as 7. 

Preparation of Aziridine-2-carbo>cflates and Aziridine-2-phosphonates I 75... 

In 1999, Bob Atkinson wrote [1] that aziridination reactions were epoxida-tion s poor relation , and this was undoubtedly true at that time the scope of the synthetic methods available for preparation of aziridines was rather narrow when compared to the diversity of the procedures used for the preparation of the analogous oxygenated heterocycles. The preparation of aziridines has formed the basis of several reviews [2] and the reader is directed towards those works for a comprehensive analysis of the area this chapter presents a concise overview of classical methods and focuses on modern advances in the area of aziridine synthesis, with particular attention to stereoselective reactions between nitrenes and al-kenes on the one hand, and carbenes and imines on the other. 

Those reactions that have found general use for the preparation of aziridines can be grouped into two broad classes addition and cyclization processes, and each of these categories can be further divided. Addition processes can be classified as being C2+N1 reactions (addition of nitrenes, or nitrene equivalents [ nitrenoids ], to alkenes Scheme 4.1) or (J N1+C1 reactions (addition of carbenes or carbenoids to imines Scheme 4.2). 

Thus, the key reason for the paucity of methods available by analogy with epox-idation methods is the comparative inertness of N-O and N-N bonds relative to the peroxide bond. This means that the synthetic methods that have been developed for preparation of aziridines are distinct from those that have evolved for epoxide synthesis. 

An alternative preparation of aziridines reacts an alkene with iodine and chloramine-T (see p. 1056) generating the corresponding A-tosyl aziridine. Bromamine-T (TsNBr Na ) has been used in a similar manner." Diazoalkanes react with imines to give aziridines." Another useful reagent is NsN=IPh, which reacts with alkenes in the presence of rhodium compounds or Cu(OTf)2 to give N—Ns aziridines. Manganese salen catalysts have also been used with this reagent. ... 

It may be concluded that the conversion of functionalized oxiranes into the corresponding aziridines by an azide ring opening followed by a Staudinger ring closure with triphenylphosphine constitutes a general method for the preparation of aziridines with high enantiopurity. 

An attractive and useful method for the preparation of aziridine-2-carboxylic esters makes use of the readily available amino acids serine and threonine. Essentially, this synthesis involves the ring closure of 1,2-amino alcohols. 

Oxide 1, when treated with primary amines like n-butyl-, cyclohexyl-, or benzylamine, gives trans-9,10-amino alcohols (264). These amino alcohols have been utilized for the preparation of aziridine 265 by treatment with trialkyl- or triarylphosphines.156... 

Several of preparations of aziridines have been reported. The aza-Darzens reaction of an fV-bromoacylcamphorsultam with iV-diphenylphosphinylimines, ArCH=N—P-(=0)Ph2, gives cz s-aziridine derivatives, except if the aryl is o-substituted, which gives significant trans product, and even 100% trans- with o-CF3.61 While steric (g) factors play a role in this inversion of selectivity, electronic effects are also important o-methyl gives a 50 50 ratio of products. 

Several studies on the reactions and preparation of aziridines have been published. The ring opening of 2-substituted aziridines, accomplished by first converting them into aziridinium salts by reaction with a benzyl bromide and then attack of the bromide counter ion, gave only one bromide in a regio- and stereo-specific reaction.43 Since attack by the bromide ion of the aziridinium salt only occurred at the most substituted carbon with an inversion of stereochemistry, it was concluded the reaction occurred by an SN2 mechanism. This was supported by calculations at the MPWBlK/6-31+G(d) level of theory for reactions featuring two solvating acetonitrile molecules embedded in an acetonitrile matrix. 

This reaction sequence allows the preparation of aziridines from 1,2-amino alcohols. 

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