Cinchona aziridination

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

Aziridination of Enones Using Cinchona-Based Chiral Phase-Transfer Catalyst... 

In 2004, Fioravanti, Pellacani, and Tardella reported the asymmetric aza-Michael-initiated ring closure additions of ethyl nosyloxycarbamate to 2-(phenylsulfanyl)-2-cycloalkenones using the cinchona-based PTCs 11 or 29, affording the corresponding aziridines with moderate ee values (Scheme 5.25) [31]. Interestingly, this reaction afforded the same enantiomer, regardless of which pseudoenantiomer of the cinchona-derived catalyst was employed. However, the absolute configuration of the products was not determined in this study. 

Minakata and coworkers also reported the asymmetric aziridination reactions of electron-deficient olefins using cinchona-based PTCs 33-37 and N-chloro-N-sodio carbamate as an oxidant [32]. Moderate values of the ee were obtained. Comparative experiments revealed that the electron-deficient olefin bearing both the dimethylpyr-azole and the di-isopropylpyrazole groups turned out to be a better Michael acceptor than that bearing the oxazolidinone substituent. The modification of the R-substit-uent of the cinchona-derived anthracenylmethylated ammonium salts 35-37 did not have any effect on the enantioselectivity (Scheme 5.26). 

In 2008, Dixon and coworkers reported catalytic enantioselective a-alkylations of [i-keto carbonyl derivatives with aziridines by using a cinchona-derived catalyst 79 (Scheme 6.23) [48]. [3-Keto carbonyl substrates 76 were reacted with N-protected... 

Aziridinations of enones using Cinchona-hased phase-transfer conditions are so far rare and have not been as successful and generally applicable as is the case for epoxidation reactions. In contrast, iminium catalysis using primaiy Cinchona-derived amines again provided excellent solutions for enone aziridination. 

Nakamura et al. reported the first highly enantioselective desymmetrisation of aziridines with phosphites catalysed by Cinchona alkaloid amides in combination with Et2Zn (Scheme 15.15). The reaction proceeds in benzene with optimally 10 mol% of both Et2Zn and iV-(2-picolinoyl)-9-amino-9-deoxy-epi-cinchonine 2, affording p-aminophosphonates in up to 90% yield and in up to 99% ee. 

The first organocatalytic asymmetric aziridination reactions of electron-deficient olefins made use of either (i) a chiral tertiary amine combined with a 0-phosphinyl or sulfonyl hydroxylamine for the in situ generation of aminimides as aziridination reagents [133, 134], or (ii) a quaternary salt of cinchona alkaloids in phase-transfer catalysis in combination with ethyl nosyloxycarbamate [135], A-acyl A-aryl... 

The second class of chiral organocatalysts recently involved in domino Michael reactions of other-than-C-nucleophiles is constituted by the cinchona alkaloid family. In this area, Melchiorre et al. have involved a chiral primary amine salt derived from 9-amino-(9-deoxy)-epz-hydroquinine to induce chirality in aziridinations of enones. This domino iminium-enamine intramolecular sequence afforded a series of chiral protected aziridines derived from both... 

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