New atropisomeric biaryl derivatives of 4-aminopyridine identification of an improved nucleophilic catalyst for asymmetric acylation of sec-alcohols

The synthesis, CSP-HPLC resolution, and absolute configuration assignment of a series of 4-dialkylaminopyridine-based atropisorneric biaryls are described. Screening of these enantiomerically pure catalysts, which differ only in the nature of the 4-dialkylamino substituent, for the kinetic resolution of 1-(1-naphthyl)ethanol reveals the importance of this group on the selectivity of catalysis. The di-n-butylamino derivative displays the most favourable catalytic profile. The utility of this catalyst for the kinetic resolution of a selection of sec-alcohols, including a precursor for the synthesis of the antidepressant fluoxetine hydrochloride (Prozac(R)) are reported. The possible role of the dialkylamino group in chirality transfer is discussed. (C) 2004 Elsevier Ltd. All rights reserved.