Development of Chiral Nucleophilic Catalysts

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A new chiral nucleophilic catalyst was developed, which consists of 4-pyrrolidinopyridine moiety as a an active site and 2-naphthylmethyl group as a stereo-controlling site. The catalyst promotes the kinetic resolution of racemic secondary alcohols through enantioselective acylation at ambient temperature. Treatment of several racemic alcohols with 5 mol % of the catalyst and 0.7 mol equivalent of isobutyric anhydride gave enantiomerically pure (>99% ee) recovered alcohols at -70 % conversion (selectivity factor (s) - 9 21).The mechanism of the catalytic asymmetric acylation was investigated by means of NOB studies of the catalyst as well as the reactive acylpyridinium intermediate. The catalyst adopts a conformation in which the pyridine ring does not interact with the naphthalene ring in its ground state. Thus, a facile reaction takes place with acid anhydride. On the other hand, close proximity of the pyridine ring with the naphthalene ring was observed in the acylpyridinium intermediate, which would be caused by the attractive pi-pi interaction between electron-deficient acylpyridinium pi-system and the electron-donating naphthalene ring. Informative NOE's suggest that the enantio-face of the carbonyl group of the acylpyridinium ion is totally controlled. The reorganization of the catalyst triggered by binding of the specific substrate (acid anhydride) is referred to as an "induced-fit" process. The process would be the key for the catalyst to show high enantio-differentiating ability without retarding its high catalytic activity.