TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 12 (2001) 3349–3365 Pergamon Asymmetric synthesis of N -aryl aziridines Joa ˜o Aires-de-Sousa, a Sundaresan Prabhakar, a, * Ana M. Lobo, a Ana M. Rosa, a,† Ma ´rio J. S. Gomes, a Marta C. Corvo, a,‡ David J. Williams b and Andrew J. P. White b a Secc ¸a ˜o de Quı ´mica Orga ˆnica Aplicada, Departamento de Quı ´mica, Centro de Quı ´mica Fina e Biotecnologia and SINTOR -UNINOVA, campus Faculdade de Cie ˆncias e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829 Monte de Caparica, Portugal b Department of Chemistry, Imperial College of Science, Technology and Medicine, South Kensington, London SW72AY, UK Received 19 November 2001; accepted 30 November 2001 Abstract—The reactions of a variety of N-arylhydroxamates as nitrogen transfer reagents to acryloyl derivatives of (-)-8-phenyl- menthol, (-)-quinine and (-)-Oppolzer’s sultam acting as Michael acceptors was studied. Poor to modest diastereoselection was observed in the formation of aziridines. The absolute structure of one of the pure diastereomers secured from Oppolzer’s auxiliary was established by X-ray crystallography and hence the absolute configuration of the derived methyl-N-phenylaziridine-2-car- boxylate could be assigned. Whilst only poor facial selectivity was observed for chiral hydroxamic acid prepared from dehydroabietic acid, moderate to good enantioselection of aziridines could be achieved with the chiral quaternary salts based on cinchona alkaloids, especially with that of cinchonine. A model is presented to explain the origin of enantioselection and a mechanism is proposed for the aziridination reaction. © 2002 Elsevier Science Ltd. All rights reserved. 1. Introduction Aziridines are valuable compounds in organic synthesis due to the regio- and stereoselective ring opening reac- tions that they undergo. 1 Chiral aziridines are of greater interest because they often serve as important synthetic precursors for many biologically useful substances. 2 We have previously described the aziridination of a variety of electron-deficient olefins with aryl hydrox- amic acids (Eq. (1), Scheme 1) and showed that the process is stereoselective. 3 Subsequently, the method was applied to a number of Michael acceptors in the presence of quaternary salts of cinchona alkaloids under phase transfer conditions (CPTC) 4 to provide chiral aziridines with varying degrees of asymmetric induction. We report herein full details pertaining to the above work and also describe various experiments made to improve the enantioselectivity of the process. Further- more, other methods consisting of addition of chiral hydroxamic acids to prochiral olefins (Eq. (3)) and vice versa (Eq. (4)) were examined and the results compared with those obtained using CPTC (Eq. (2)). Scheme 1. * Corresponding author. Tel.: +351-21-2948387; fax: +351-21- 2948550; e-mail: sp@dq.fct.unl.pt † Present address: A ´ rea Departamental de Quı ´mica, Faculdade de Cie ˆncias e Tecnologia, Universidade do Algarve, campus de Gam- belas, 8000 Faro, Portugal. ‡ In partial fulfilment of the requirements of the graduate course. 0957-4166/01/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0957-4166(01)00548-1