Biomimetic Catalytic Retro-Aldol Reaction Using a Cation-Binding Catalyst: A Promising Route to Axially Chiral Biaryl Aldehydes.

Here we describe a biomimetic catalytic retro-aldol reaction of racemic α-substituted ß-hydroxy ketones utilizing a chiral oligoEG cation-binding catalyst as a type-II aldolase mimic. Our investigation of various aldol substrates has demonstrated that our biomimetic retro-aldol protocol enables rapid access to highly enantiomerically enriched aldols with a selectivity factor (s) of up to 70. Additionally, we have demonstrated the synthetic strategy's feasibility for accessing diverse and valuable axially chiral aldehydes.

Bio-inspired Water-Driven Catalytic Enantioselective Protonation.

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.

Hydrophobic chirality amplification in confined water cages.

The manipulation of the transition states of a chemical process is essential to achieve the desired selectivity. In particular, transition states of chemical reactions can be significantly modified in a confined environment. We report a catalytic reaction with remarkable amplification of stereochemical information in a confined water cage. Surprisingly, this amplification is significantly dependent on droplet size. This water-induced chirality amplification stems from the hydrophobic hydration effects, which ensures high proximity of the catalyst and substrates presumably at the transition state, leading to higher enantioselectivity. Flow and batch reactors were evaluated to confirm the generality of this water-induced chirality amplification. Our observation on efficient chiral induction in confined water cages might lead to an understanding of the chirality amplification in the prebiotic era, which is a key feature for the chemical evolution of homochirality.