Aziridination of imines

An alternative approach to aziridine synthesis involves transfer of a carbenoid species to imines. Jacobsen achieved the first asymmetric aziridination of imines by transfer of copper carbenoids derived from copper bis-oxazohne catalysts and ethyl diazoacetate onto imines, but this process only proceeds with moderate yield and selectivity. Better results have been achieved by addition of ethyl diazoacetate to imines in the presence of enantiopure Lewis acids such as the boron-based catalysts prepared from vaulted biaryls such as VAPOL (4.154) and B(OPh)3. A range of aryl and alkyl N-benzylaldimines, for example (4.155) and (4.156), undergo aziridination to give ds-aziridines with high ee using this procedure. 

The sulfoniutn ylide-mediated epoxidation procedure developed by Aggarwal (see Section 4.8) has been adapted to the enantioselective synthesis of aziridines from imines bearing electron withdrawing groups on nitrogen. The 

Colladon, A. Scarso, P. Sgarbossa, R. A. Michelin andG. Strukul, J. Am. Chem. Soc,. 

Mukaiyama, T. Yamada, T. Nagata and K. Imagawa, Chem.Lett., 1993, 327. 

Watanabe, Y. Kobayashi, T. Arai, H. Sasai, M. Bougauchi and M. Shibasaki, Tetrahedron Lett., 1998, 39,7321. 

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A variety of methods for the asymmetric syntheses of aziridine-2-carboxylates have been developed. They can be generally classified into eight categories based on the key ring-forming transformation and starting materials employed (i) cyclization of hydroxy amino esters, (ii) cyclization of hydroxy azido esters, (iii) cyclization of a-halo- and ot-sulfonyloxy-(3-amino esters, (iv) aziridination of ot, 3-unsaturated esters, (v) aziridination of imines, (vi) aziridination of aldehydes, (vii) 2-carboxylation of aziridines, and (viii) resolution of racemic aziridine-2-carboxylates. 

The synthesis of aziridines through reactions between nitrenes or nitrenoids and alkenes involves the simultaneous (though often asynchronous vide supra) formation of two new C-N bonds. The most obvious other alternative synthetic analysis would be simultaneous formation of one C-N bond and one C-C bond (Scheme 4.26). Thus, reactions between carbenes or carbene equivalents and imines comprise an increasingly useful method for aziridination. In addition to carbenes and carbenoids, ylides have also been used to effect aziridinations of imines in all classes of this reaction type the mechanism frequently involves a stepwise, addition-elimination process, rather than a synchronous bond-forming event. 

Williams and Johnston have reported the first use of proton catalysis in the aziridination of imines by diazoesters (Scheme 4.30) [38]. A range of aryl and ali-... 

Rh-catalysed aziridinations of imines with [2.2.2] bicyclic sulfide ligand. 

A review has appeared on the synthesis of enantiomerically enriched aziridines by the addition of nitrenes to alkenes and of carbenes to imines.45 A study of the metal-catalysed aziridination of imines by ethyl diazoacetate found that mam group complexes, early and late transition metal complexes, and rare-earth metal complexes can catalyse the reaction.46 The proposed mechanism did not involve carbene intermediates, the role of the metal being as a Lewis acid to complex the imine lone pah. Ruthenium porphyrins were found to be efficient catalysts for the cyclopropana-tion of styrenes 47 High diastereoselectivities in favour of the //-product were seen but the use of chiral porphyrins gave only low ees. 

The aziridination of imines catalyzed by the CpFe(CO)2+ fragment by carbene transfer is a most remarkable reaction [26], The imine is consumed first to form both the cis and trans products. The catalyst then coordinates predominantly to the trans product and leads to its decomposition, leaving the cis product untouched [27]. 

Aggarwal, V. K. Ferrara, M. Highly selective aziridination of imines using trimethylsilyl-diazomethane and applications of C-silylaziri-dines in synthesis. Org. Lett. 2000, 2, 4107-4110. 

General Procedure for Aziridination of Imines using Chiral Sulfide Catalyst [49] (p. 378)... 

Finally, analogous to the epoxides, aziridines can also be prepared by the addition of carbenoid centers to a carbon-nitrogen double bond. In this arena, Aggarwal and co-workers have reported a highly diastereoselective aziridination of imines with trimethylsilyldiazo-methane (TMSD). Thus, tosylimine 146 was converted to the cis aziridine 147 in 65% yield <02JOC2335>. 

Reaction of 7V-benzylidine-o-anisidine with ethyl diazoacetate as the carbene-donor fragment in the presence of SnCU as the catalyst (5 mol %) gives the cw-aziridine selectively as the catalyst in reasonable yields (Eq. 65) [98], In the presence of SnCU no reaction occurs. This imine-SnC intermediate gives important information about the reaction course for the Lewis acid-catalyzed aziridination of imines. 

DFT has been used to study the copper(l)-catalysed aziridination of imines by diazoacetate. ... 

Note (5)-VAPOL is an organic derivative of phosphoric acid that acts as an exceptional chiral organocatalyst promoting Diels-Alder and aldol reactions as well as aziridination of imines. The mechanism of its catalytic activity has been studied by physico-chemical and computational methods, but is still not completely... 

Stereoselective aldol reactions, allylations, and aziridinations of imines, including activated imines, have been reported." The Sakurai-Hosomi reaction of aUylsilane with imine in the presence of tetrabutylammonium fluoride is found not to be strictly catalysed by fluoride rather, a fluoride-triggered autocatalytic route is suggested. 

Scheme 20.14 Aziridination of imines for the synthesis of vinyl aziridines.

Aziridines can be formed by nitrene (-like) additions to double bonds, or by carbene (-like) additions to imines. Both processes especially the latter one can also occur by a stepwise addition-elimination process [172]. Similar to cyclopropa-nations, aziridinations of imines can foUow two protocols alkylation-deprotonation-substitution and sulfide reactions with metallocarbenes. 

Table 7.22 Diastereoselective aziridination of imines catalyzed by dimethylsulfide (137)...

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