Aziridination, of alkenes

So far aziridination reactions have, in some ways, had more in common with cyclopropanation reactions (see Section 9.1) than with epoxidation reactions. Nevertheless, the aziridination reaction is more synthetically akin to epoxidation, and on that basis, is included in the present chapter. Aziridines maybe prepared by nitrene transfer to alkenes or by carbene transfer to imines and both approaches have been performed in an enantioselective sense using enantiomerically pure metal-based catalysts. 

Most manganese(III)(salen) complexes have generally been found to be less effective for aziridination than for epoxidation, both in terms of enantioselectivity and yield. However, the salen complex (4.149) has been shown to give high enantioselectivity for some simple alkenes such as styrene (4.75) that undergo 

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These reagents may be considered to be one of the elusive aza-analogues of peroxyacids, and there are significant mechanistic similarities between the Rees-Atkinson reaction and the Bartlett epoxidation. Chiral Q-reagents have been used to effect highly stereoselective aziridination of alkenes (Scheme 4.13) [1],... 

Since the mid-1990s, synthetic attention has been directed more towards the use of metal-stabilized nitrenes as synthetic effectors of alkene aziridination. In 1969 it was reported that Cu(i) salts were capable of mediating alkene aziridination when treated with tosyl azide, but the method was limited in scope and was not adopted as a general method for the synthesis of aziridines [12]. Metaloporphyrins [13] were shown to be catalysts for the aziridination of alkenes in the presence of the nitrene precursor N-tosyliminophenyliodinane [14] in the early 1980s, but the reaction did... 

Chloramine-T also functions as a nitrene source in the presence of heteropoly acids (HPAs) such as phosphomolybdic and phosphotungstic acids. The aziridination of alkenes by treatment with the combination of HPA and chloramine-T is... 

Bromamine-T can also be utilized as a nitrene source, as reported by Zhang et al. [27]. Fe(in) porphyrins such as Fe(TPPC)Cl (Figure 4.2) thus catalyze the aziridination of alkenes when bromamine-T is used, whereas chloramine-T was inactive and iodinanes were inefficient reagents. 

A dinuclear iron(ll/Ill) complex bearing a hexadentate phenol ligand displayed moderate activity toward aziridination of alkenes with PhlNTs a large excess of alkene (2,000 equiv. vs PhlNTs) was required for good product yields (Scheme 22) [76]. It is noteworthy that complex 4 is active in the aziridination of aliphatic alkenes, affording higher product yields than copper (11) catalysts with tetradentate macrocyclic ligands [77]. 

The aziridination of alkenes catalysed by [CuCl(IPr)] complex 150 was used in a key step of the total synthesis of (+)-agelastatin 152 (Scheme 5.39) [44], The aziridination occurs in presence of 50 mol% of 150 in 52% yield. It is important to note that 150 was the only complex able to promote the aziridination of 149, an electron-deficient cyclopentene. 

Aziridination of alkenes can be carried out using N-(p- to I ucncsu I I o n y I i m i n o) phenyliodinane and copper triflate or other copper salts.257 These reactions are mechanistically analogous to metal-catalyzed cyclopropanation. Rhodium acetate also acts as a catalyst.258 Other arenesulfonyliminoiodinanes can be used,259 as can chloroamine T260 and bromoamine T.261 The range of substituted alkenes that react includes acrylate esters.262... 

Che et al. have reported that chiral Ru11(salen)s (54a) and (54b) are efficient catalysts for aziridination of alkenes (up to 83% ee) and amidation of silyl enol ethers (up to 97% ee), respectively (Scheme 39).163... 

F. Aziridination of Alkenes with Chiral Diimine-based Catalysts. 119... 

Iodine was found to be an efficient catalyst for the aziridination of alkenes (Scheme 6) utilizing chloramine-T (A-chloro-A-sodio-p-toluenesulfonamide) as the nitrogen source. For example, when 2 equiv. of styrene (45a) were added to chloramine-T in the presence of a catalytic amount of iodine (10mol%) in a 1 1 solvent mixture of acetonitrile and neutral buffer, the corresponding aziridine (46) was obtained in 91% yield. The reaction proved to work with other acyclic and cyclic alkenes, such as oct-l-ene and cyclohexene. The aziridination of para-substituted styrene derivatives (45b-e) demonstrated that, as expected for an electrophilic addition, electron-rich alkenes reacted faster than electron-poor alkenes. However, with 1 equiv. of I2, mainly iodohydrin (47) was formed. A catalytic cycle has been proposed to account for the fact that only a catalytic amount of iodine is required (Scheme 1) ... 

There have also been significant advances in the imido chemistry of ruthenium and osmium. A variety of imido complexes in oxidation states +8 to +6 have been reported. Notably, osmium (VIII) imido complexes are active intermediates in osmium-catalyzed asymmetric aminohydroxyl-ations of alkenes. Ruthenium(VI) imido complexes with porphyrin ligands can effect stoichiometric and catalytic aziridination of alkenes. With chiral porphyrins, asymmetric aziridination of alkenes has also been achieved. Some of these imido species may also serve as models for biological processes. An imido species has been postulated as an intermediate in the nitrite reductase cycle. " ... 

The mechanism of the copper-catalyzed aziridination of alkenes using 44 as the nitrene source has been described with the steps shown in Scheme 12.10 contributing... 

A general method for direct aziridination of alkenes, discovered nearly thirty years ago, involved oxidation of a number of A-aminoheterocyclic compounds, such as 240, with lead tetraacetate (LTA) in the presence of the alkene to give 241 375. The intermediates in these aziridinations were originally believed to be the corresponding TV-nitrenes but have recently been shown to be (at least for A-aminoquinazolinone 240 and A-aminophthalimide) the corresponding A-acetoxyamino compounds 242375. 

For example, Jacobsen has studied the asymmetric aziridination of alkenes using (diimine)-copper(I)-catalysts 85. The results support the intermediacy of a discrete Cu(III)-nitrene intermediate and thus suggests mechanistic similarity (particularly regarding transition state geometry) to asymmetric cyclopropanation [95JA5889]. 

Metal-catalysed aziridination of alkenes by [(Ar-tosylimino)iodo]benzene... 

Heterogeneous asymmetric aziridination of alkenes with CuHY... 

In this paper we have described a design approach for heterogeneous enantioselective catalysts. The approach is based upon modification of the counter-cation of zeolites or mesoporous alumino-silicates with a suitable chiral ligand.7 We have demonstrated the approach with two examples (a) enantioselective aziridination of alkenes using Cu2+-exchanged zeolite Y modified with chiral oxazolines and (b) the modification of... 

The nitrogen source for the aziridination of alkenes, a nitrene or nitrenoid, can be generated in various ways (1) oxidation of a primary amine (2) base-induced -elimination of HX from an amine or amide with an electronegative atom X (X = halogen, O) attached to the NH group or by -elimination of metal halides from metal A-arenesulfonyl-A-haloamides (3) metal-catalyzed reaction of [A-(alkane/arenesulfonyl)imino]aryliodanes (4) thermolytic or photolytic decomposition of organyl azides and (5) thermally induced cycloreversion reactions . 

Several reagents will effect the aziridination of alkenes directly, for example, electrophilic alkenes react with diphenylsulfilimine (1) in good yield, with the elimination of diphenyl sulfide (Scheme l). A similar reaction using the chiral sulfilimine (R)-(-t-)-(3) gives product (2 96%) as the (2R.3S) form shown (64%). accompanied by the enantiomer (32%). Cephalosporin substrates (4) react with achiral (1) to give pn ucts (5), as single diastereoisomers in 52-63% yields. ... 

Gabriel and Wenker type syntheses are thoroughly viable for IV-alkylaziridines, and diere are examples of aziridination of alkenes, via vic-dihalides etc., where by use of a chiral amine a kinetic induction of chirality in the aziridine nucleus has been achieved. 2-Iodoalkyl aades react with alkyl and aryl dichloroboranes, forming aziridines (Scheme 17). Sequences resembling the Wittig and Wittig-Hor-... 

Terminal epoxides of high enantiopurity are among the most important chiral building blocks in enantioselective synthesis, because they are easily opened through nucleophilic substitution reactions. Furthermore, this procedure can be scaled to industrial levels with low catalyst loading. Chiral metal salen complexes have also been successfully applied to the asymmetric hydroxylation of C H bonds, asymmetric oxidation of sulfides, asymmetric aziridination of alkenes, and the asymmetric alkylation of keto esters to name a few. 

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