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 atropisomeric 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®) are reported. The possible role of the dialkylamino group in chirality transfer is discussed.