ja0c11815_si_001.pdf (9.97 MB)
Download file

Bio-inspired Water-Driven Catalytic Enantioselective Protonation

Download (9.97 MB)
journal contribution
posted on 13.01.2021, 19:34 authored by Si Joon Park, In-Soo Hwang, Young Jun Chang, Choong Eui Song
Catalytic enantioselective protonation of a prochiral carbanion in water is a common transformation in biological systems, but has been beyond the capability of synthetic chemists since unusually rapid movement of a proton in water leads to uncontrolled racemic protonation. Herein we show a crucial role of water, which enables a highly enantioselective glyoxalase I-mimic catalytic isomerization of hemithioacetals which proceeds via enantioselective protonation of an ene-diol intermediate. The use of on-water condition turns on this otherwise extremely unreactive catalytic reaction as a result of the strengthened hydrogen bonds of water molecules near the hydrophobic reaction mixture. Furthermore, under on-water conditions, especially under biphasic microfluidic on-water conditions, access of bulk water into the enantio-determining transition state is efficiently blocked, consequently enabling the enantioselective introduction of a highly ungovernable proton to a transient enediol intermediate, which mimics the action of enzymes.