Catalytic Asymmetric Hydration of Alkenes

Abstract

The asymmetric Markovnikov hydration of alkenes to alcohols, transforming abundant feedstock chemicals and water into synthetically versatile building blocks, has long remained inaccessible. The reaction is inherently reversible because of unfavorable entropy, preventing asymmetric induction. While lowering the temperature should favor product formation in principle, such conditions are normally incompatible with the required protonation of simple alkenes and with maintaining a homogeneous reaction mixture. Here we show that this long-standing limitation is overcome by making catalytic activity viable under cryogenic conditions. Using confined strong Bro̷nsted acid catalysts and solvent-organized hydrogen-bonding networks that facilitate protonation of otherwise unreactive alkenes, we achieve a highly enantioselective hydration of electronically neutral alkenes with water. This thermodynamic temperature dependence also allows conversion of racemic tertiary alcohols into enantioenriched forms through a one-pot formal deracemization. Experimental and computational studies indicate that perfluorinated solvents form extended hydrogen-bonding networks that enhance both reactivity and stereocontrol. These findings establish a general strategy for overcoming fundamental constraints imposed by reversibility.