Enantiomerically enriched aziridines

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. 

Another example of the C + C=N" pathway involves the addition of stabilized sulfonium ylides onto A-tosylimines. This is operationally a straightforward procedure under phase-transfer conditions <97TL7225>, and the use of a chiral auxiliary allows the preparation of enantiomerically enriched aziridines, as illustrated by the reaction of A -sulfonylimine 132 with chiral sulfonium propargylide 133 to give the chiral aziridine 134 <97AG(E)1317>. 

Metal salt catalyzed conjugate addition of nitrogen nucleophiles has attracted considerable interest as means to access valuable intermediates for the preparation of P-amino acid, P-lactams, isoxazolidinones, aziridines, and so on. However, enantios-elective Cu(II)-catalyzed reactions of this type are limited. Cardillo and coworkers reported the Cu(OTf)2/Bn-BOX (32)-catalyzed additions of O-benzylhydroxylamine (230) and N,0-bis(trimethylsilyl)hydroxylamine (232) to alkylidene malonates (219) (Scheme 17.49) [68]. Yields and enantioselectivities ofthedesired P-amino carbonyl compounds (231) and (233) are moderate to good under optimized conditions. In the latter case the conjugate addition products are readily converted to enantiomerically enriched aziridines (234) in good yields. 

A-Sulfonylaldimines produced by condensation of SES-NFI2 with various aldehydes are converted into enantiomerically enriched aziridines upon reaction with certain sulfur ylides. The same types of aldimines undergo [3 4- 2] cycloaddition reactions with 2,3-butadienoates in the presence of triphenylphosphine to give 2,5-dihydrop3TToles, while that derived from SES-NSO and ethyl glyoxylate reacts efficiently with chiral sulfonimidoyl substituted bis(allyl)titaniumcorr5)lexes to give /3-alkyl-)/,5-unsaturated a-amino acid derivatives. ... 

Activated aziridines should be as useful as epoxides for carbon-carbon bond formation, with the advantage that the product will already incorporated the desired secondary aminated stercocentcr. To date, a general enantioselective method for the aziridination of alkcncs has not been developed. Eric Jacobsen of Harvard University (Angew. Chem. hit. Ed. 2004,43, 3952) has explored an interim solution, based on the resolution of racemic epoxides such as I. The cobalt catalyst that selectively hydrolyzes one enantiomer of the epoxide also promotes the addition of the imidc to the remaining enantiomerically-enriched epoxide. As expected, the aziridine 4 is opened smoothly with dialkyl cuprates. 

Suitable enamines can react with (ethoxycarbonyl)nitrene, generated from ethyl 7V-(4-nitrophenylsulphoxy)carbamate, giving relatively unstable aziridines103. Diaster-eoselective attack of this nitrene on the double bond of chiral enamine 98 and opening of the intermediate aziridine (197) afforded enantiomerically enriched 2-ethoxycarbony-laminocyclohexanone 198104,105 (equation 42). 

Cyclic and acyclic enol derivatives 480 can be asymmetrically aziridinated with (A -tosylimino)iodobenzene 481 using a chiral copper catalyst prepared in situ from [Cu(MeCN)4]PF6 and the optically active ligand 479. Collapse of the aminal (i.e., 482) leads to the formation of enantiomerically enriched Q-amino carbonyl compounds 483, although ee s to date are modest <2000EJ0557>. Similarly, dienes can be selectively aziridinated using the chiral Mn-salen complex 484 to give vinyl aziridines 486 in scalemic form (Scheme 124) <2000TL7089>. 

Diels-Alder reactions of enantiomerically enriched 2H-azirine 3-phosphon-ates (281), a new class of chiral iminodienophiles, and dienes stereoselectively furnish optically pure, bicyclic aziridine adducts (282). Hydrogenation of (282) results in a ring opening that affords the first examples of optically pure quaternary piperidine phosphonates. Two step synthesis of an enantiomeric pure cyclic phosphite (283) and its application as a chiral phosphorus nucleophile in the asymmetric Michael addition to nitroalkenes (284) provides an efficient... 

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