Resin-Immobilized Palladium Acetate and Alcohol Dehydrogenase for Chemoenzymatic Enantioselective Synthesis of Chiral Diarylmethanols.

Abstract

The enantioselective synthesis of chiral diarylmethanols is highly desirable in synthetic chemistry and the pharmaceutical industry, but it remains challenging, especially in terms of green and sustainable production. Herein, a resin-immobilized palladium acetate catalyst was fabricated with high activity, stability, and reusability in Suzuki cross-coupling reaction of acyl halides with boronic acids, and the coimmobilization of alcohol dehydrogenase and glucose dehydrogenase on resin supports was also conducted for asymmetric bioreduction of diaryl ketones. Experimental results revealed that the physicochemical properties of the resins and the immobilization modes played important roles in affecting their catalytic performances. These two catalysts enabled the construction of a chemoenzymatic cascade for the enantioselective synthesis of a series of chiral diarylmethanols in high yields (83-90%) and enantioselectivities (87-98% ee). In addition, the asymmetric synthesis of the antihistaminic and anticholinergic drugs (S)-neobenodine and (S)-carbinoxamine was also achieved from the chiral diarylmethanol precursors, demonstrating the synthetic utility of the chemoenzymatic cascade.