Key Points
- World’s first successful synthesis of alcohols with controlled molecular “hand” orientation using only feedstock chemicals and water.
- Achieved stereocontrol—previously considered impossible in principle—by applying a counterintuitive approach that works best at extremely low temperatures.
- The hydrogen-bonding network between the catalyst and perfluorinated solvent—key to stereocontrol—was elucidated through crystallographic and computational analysis.
Overview
A research group led by Specially Appointed Assoc. Professor Nobuya Tsuji and Specially Appointed Prof. Benjamin List at WPI-ICReDD, Hokkaido University has achieved a world-first success in precisely controlling the “right-handed or left-handed” (chirality) configuration of molecules when synthesizing alcohols by directly adding water to alkenes, which are feedstock chemicals. While the idea of “mixing feedstocks with water to produce alcohols stereoselectively” may sound far-fetched, this is the essence of this research. Alkenes, which are obtained in large quantities during petroleum refining, are a rich resource with great potential for conversion into high-value-added compounds such as pharmaceuticals and fragrances. Since the pharmacological effects and safety of the resulting alcohols vary significantly depending on their chirality, controlling the “handedness” has become a critical challenge in manufacturing. While the reaction of synthesizing alcohols by adding water to alkenes has been known for a long time, controlling it has been extremely difficult due to a fundamental thermodynamic constraint: the reaction tends to proceed backwards easily. In particular, precise control of chirality was long considered “impossible in principle”.
In this study, a counterintuitive idea—that “the colder it is, the better it works”—proved to be the breakthrough. In this reaction, where two molecules combine into one, lowering the temperature weakens the tendency toward the reverse reaction, allowing the reaction to proceed stably. Under cryogenic conditions, racemization due to the reverse reaction is thermodynamically suppressed, and by combining the “IDPi catalysts”—which feature strong acidity and a precise three-dimensional structure—with perfluorinated solvents, the researchers simultaneously achieved high yields and high enantioselectivity (up to 97.5 : 2.5). The hydrogen-bonding network between the catalyst and the perfluorinated solvent, which is key to stereocontrol, was elucidated through crystal structure analysis and computational chemistry. Furthermore, the method has been successfully applied to the synthesis of natural products and the one-pot conversion (deracemization) of racemic alcohols, and is expected to contribute to a wide range of industrial fields, including drug discovery, fragrances, and functional materials. These research findings were published online in the Journal of the American Chemical Society on Tuesday, June 2, 2026.
