Rapid, room-temperature acylative kinetic resolution of sec-alcohols using atropisomeric 4-aminopyridine/triphenylphosphine catalysis

Two new atropisomeric 4-aminopyridine-based nucleophilic catalysts containing terphenyl ‘blocking groups’ have been prepared and evaluated for kinetic resolution (KR) of aryl alkyl sec-alcohols. One of these biaryls is shown to be the most selective atropisomeric catalyst yet prepared for several sec-alcohols but its low reactivity makes it non-optimal for use at room temperature (rt). Optimisation of the conditions for conducting KRs at rt using a previously described catalyst (containing a phenyl blocking group) at the 1 mol% level indicates that PPh3 (1 equiv) is beneficial for enantioselectivity and allows KR of (±)-1-(naphthyl)ethanol in less than 30 min with s>15 (i.e., ∼40% recovered alcohol with >95% ee). These conditions constitute a convenient and practical method for rapid KR of sec-alcohols and are anticipated to facilitate a detailed kinetic study of this catalytic manifold by calorimetry.