The use of chiral nonracemic onium salts and crown ethers as effective phase-transfer catalysts have been studied intensively primarily for enantioselective carbon-carbon or carbon-heteroatom bond-forming reactions under mild biphasic conditions. An essential issue for optimal asymmetric catalysis is the rational design of catalysts for targeted reaction, which allows generation of a well-defined chiral ion pair that reacts with electrophiles in a highly efficient and stereoselective manner. This concept, together with the synthetic versatility of phase-transfer catalysis, provides a reliable and general strategy for the practical asymmetric synthesis of highly valuable organic compounds.

A series of C(2)-symmetric chiral quaternary ammonium bromides 10 and 11 have been designed as a new, purely synthetic chiral phase-transfer catalyst, and readily prepared from commercially available optically pure 1,1'-bi-2-naphthol as a basic chiral unit. The details of the synthetic procedures of each requisite chiral binaphthyl subunit have been disclosed, and the structures of the assembled N-spiro chiral quaternary ammonium bromides 11a and 11f were unequivocally determined by single-crystal X-ray diffraction analysis. The reactivity and selectivity of these chiral ammonium bromides as chiral phase-transfer catalysts have been evaluated in the asymmetric alkylation of the benzophenone Schiff base of glycine ester 7 under mild liquid-liquid phase-transfer conditions, and the optimization of the reaction variables (solvent, base, and temperature) has also been conducted. Further, the scope and limitations of this asymmetric alkylation have been thoroughly investigated with a variety of alkyl halides, in which the advantage of the unique N-spiro structure of 11 and dramatic effect of the steric as well as the electronic properties of the aromatic substituents on the 3,3'-position of one binaphthyl moiety have been particularly emphasized. Finally, the potential synthetic utility of the present method for the practical asymmetric synthesis of structurally diverse natural and unnatural alpha-amino acids has been demonstrated by its successful application to the facile asymmetric syntheses of (S)-N-acetylindoline-2-carboxylate, a key intermediate in the synthesis of the ACE inhibitor, and l-Dopa (l-3,4-dihydroxyphenylalanine) ester and its analogue.

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Despite the increasing importance and usefulness of phase transfer catalysis (PTC) in synthetic organic reactions, 1 catalytic asymmetric synthesis utilizing chiral phase-transfer catalysts remains poorly studied. [2][3][4] Yet, since the pioneering work of O 'Donnell et al. in 1989, asymmetric synthesis of R-amino acids by phase-transfer enantioselective alkylation of a prochiral protected glycine derivative 1 using a chiral catalyst has provided an attractive method for the preparation of both natural and unnatural amino acids. 5 Recently, the Corey 6 and Lygo groups 7 independently reported an impressive departure from the previous results in terms of enantioselectivity and general applicability. However, almost all of the elaborated chiral phase-transfer catalysts reported so far have been restricted to cinchona alkaloid derivatives, which unfortunately constitutes a major difficulty in rationally designing and fine-tuning catalysts to attain sufficient reactivity and selectivity for various chemical transformations under phase-transfer catalyzed conditions. 3,4 In this paper, we wish to describe a new, rational approach to this subject, i.e., the molecular design of a C 2 -symmetric chiral quaternary ammonium salt and its successful application to the highly efficient, catalytic enantioselective alkylation of tert-butyl glycinate-benzophenone Schiff base 1 under mild phase-transfer conditions.