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.