Kinetic resolution of α-substituted alkanoic acids promoted by homobenzotetramisole

Abstract

A new method for catalytic nonenzymatic kinetic resolution of α-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, α-aryl-, α-aryloxy/alkoxy-, α-halo-, α-azido-, and α-phthalimido-alkanoic acids. Under similar conditions, α-(arylthio/alkylthio)-alkanoic acids undergo dynamic kinetic resolution providing corresponding esters in up to 92% ee and up to 93% yield.