Sterically Hindered Ketiminium Salts: a New Generation of Phase-Transfer Catalysts S. Gmouh, a J. Jamal-Eddine a, * and J. Y. Valnot b,² a Universite  Hassan II Aõ Èn-Chock, Faculte  des Sciences, UFR de Chimie Organique. B.P. 5366 Maa Ãrif-Casablanca, Morocco b Laboratoire des Fonctions Azote Âes et Oxyge Âne Âes Complexes IRCOF-UPRESA 6014 76821 Mont Saint Aignan Ce Âdex, France Received 6 June 2000; revised 8 August 2000; accepted 23 August 2000 Abstract ÐSterically hindered hydrazone 2 undergoes an unpredicted N±N bond scission via a methiodination sequence leading to iminium salt 5. This latter compound was found to be remarkably stable under basic and acidic conditions and it proved to be able to promote C-alkylation of the glycine derived imine 7 under classical catalytic liquid±liquid phase-transfer conditions. Both the reaction cleavage and the catalytic potential are discussed. q 2000 Elsevier Science Ltd. All rights reserved. Introduction Asymmetric phase-transfer catalysis (PTC) has attracted considerable attention as a convenient technique for the synthesis of chiral molecules. 1 The effectiveness of phase- transfer catalysts derived from cinchona alkaloids in different types of asymmetric reactions has triggered the development of a variety of modi®ed quaternary ammonium salts either to improve the optical yields or to determine the geometrical factors that control the observed stereo- selectivities. 2 As part of an ongoing research programme aimed to develop new phase-transfer agents and to contribute to original ideas in the ®eld, we recently suggested non-cinchona alkaloid catalysts based on benzophenone proline hydrazonium salts. 3 These species have been designed following a methodology of ion-pair structure control approach. Although they possess high catalytic properties in the alkyl- ation of Schiff bases, their low resistance to hydrolysis resulted in erratic enantioselective alkylation reproduci- bility. In order to further explore the catalytic potency of such a system it appeared essential to strengthen the ketimine moiety by providing more steric hindrance as it has been shown that sterically crowded imines resist hydrolysis. 4 Molecular models indicated that the introduction of two naphthyl groups in the ketimine part provides a structure which not only respects the required steric and electronic environment, but also might possess further stereoface differentiating ability. Unfortunately, the catalyst candidate could not be prepared because of an unpredicted methyl iodide-mediated N±N bond cleavage during the quaternisa- tion step, leading to an iminium salt instead. This latter showed high stability and was found to possess a great deal of potential as a phase-transfer catalyst. Before dis- closing these catalytic properties, we shall ®rst focus on the hydrazone cleavage. Results and Discussion The preparation of sterically hindered 1-bisnaphthylmethyl- idenamino-2-(S)-hydroxymethylpyrrolidine 2 has been carried out following a modi®ed transimination protocol between bisnaphthylmethylidenamine 1 and 1-amino-2- (S)-hydroxymethylpyrrolidine 5 (Scheme 1). The best result was obtained by slowly adding the hydrazine to a re¯uxing solution of imine 1 in 1,2-dichloroethane. This mode of addition results in the formation of a substantial amount of hydrazone during the ®rst hours of the reaction and probably limits the side reactions that competed with transimination under standard conditions. 6 The course of the quaternisation step proved to be highly solvent dependent since no reaction has been observed in benzene, benzene/ethanol mixture or in methyl iodide. Thus, heating hydrazone 2 with excess methyl iodide in acetonitrile for a period of 30 h led to a dark heterogeneous reaction medium. Filtration of the less soluble material and recrystallisation from acetonitrile surprisingly gave the N,N-dimethyl-bisnaphthylmethylidenammonium iodide 5 as a yellow solid. This compound was unambiguously characterised by comparison with an authentic sample prepared independently in 67% yield by methiodination of Tetrahedron 56 (2000) 8361±8366 Pergamon TETRAHEDRON 0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(00)00779-1 Keywords: hydrazone; cleavage reaction; phase-transfer; iminium salt; amino acids. * Corresponding author. Tel.: 1212-2-23-06-80; fax: 1212-2-23-06-74; e-mail: j.eddine@facsc-achole.ac.ma ² Fax: 133-2-35-52-29-71; e-mail: jean-yves.valnot@univ-rouen.fr.