Kinetic Resolution of α-Substituted Alkanoic Acids Promoted by Homobenzotetramisole

A new method for catalytic nonenzymatic kinetic resolution of alpha-substituted alkanoic acids has been developed, which relies on their activation with DCC followed by enantioselective alcoholysis of the intermediate symm-anhydrides in the presence of the amidine-based catalyst homobenzotetramisole (HBTM). Moderate to excellent selectivity factors (s = 5-96) have been obtained in the case of several classes of substrates, namely, alpha-aryl-, alpha-aryloxy/alkoxy-, alpha-halo-, alpha-azido-, and alpha-phthalimido-alkanoic acids. Under similar conditions, alpha-(arylthio/alkylthio)-alkanoic acids undergo dynamic kinetic resolution providing corresponding esters in up to 92% ee and up to 93% yield.