Cinchoninium Boronate Ion Pair-Catalyzed Enantioselective Desymmetrization of 1,3-Diols

The combination of a chiral cationic phase-transfer catalyst (ccPTC) and inorganic bases for asymmetric synthesis has been well demonstrated. However, this strategy is inapplicable for the asymmetric functionalization of weakly acidic pronucleophiles such as diols, in which weak bases are unable to efficiently activate the alcohol but strong bases lead to a racemic background reaction. To resolve the dilemma, a catalytic system of ccPTC with readily available achiral hemiboronic and borinic acids capable of activating diols under mild conditions was thus developed. Herein, an enantioselective O-alkylative desymmetrization of 2-substituted and 2,2-disubstituted 1,3-diols by merging cinchoninium with achiral boron catalysts was achieved. Moreover, the synergistic cooperation between them was supported by 11B NMR analysis, the Rotating-frame Overhauser Enhancement Spectroscopy (ROESY) experiment, and kinetic studies, providing detailed mechanistic insights into the catalytic and stereocontrol model.