Chiral Mitsunobu reactions with (1 S)-(+)-ketopinic acid: kinetic resolutions of secondary alcohols

Abstract

Several secondary alcohols undergo the Mitsunobu reaction with triphenylphosphine, diethyl azodicarboxylate and (1 S)-(+)-ketopinic acid (0.5 equiv. each relative to alcohol) in CH 2Cl 2 solution at −23°C, to furnish the chiral secondary alcohol and its ketopinate ester (d.e. >95%). Chromatographic separation of these and subsequent hydrolysis of the ketopinate ester (KOH/EtOH/0°C) provides the chiral secondary alcohol in overall yields of ∼75% and e.e. of ∼80%. When the above Mitsunobu reaction is performed with 1 equiv. of all the reactants, an effective dynamic kinetic resolution of the alcohol is observed in two cases, the ketopinate esters being isolated in 63 and 75% yields and >95% d.e.