Background: Conducting organic reactions in water as a solvent have attracted chemists
because of its environmentally benign property. However, it often suffers practical difficulties since
most of organic compounds are insoluble in water. One promising methodology to improve the reactivity
in water is to use surfactants that emulsify the organic/water mixture. Efficient extraction from
the emulsified mixture is necessary to reduce the usage of organic solvent.
Methods: We designed polymer micelle that can be turned on and off by temperature-stimuli. Poly(Nisopropyl
acrylamide), known as thermoresponsive polymer, was copolymerized with the acrylate ester of 4-hydroxy-Lproline
using a reversible addition/fragmentation chain transfer polymerization (RAFT) reagent that contains a
poly(ethylene glycol) (PEG) chain to obtain a polymer-tethered organocatalyst. The L-proline moieties were immobilized
on a thermoresponsive amphiphilic diblock copolymer that consists of poly(N-isopropyl acrylamide) (PNIPAAm) and linear
PEG fragments. The copolymer dissolved in water to form clear solution at room temperature, whereas the solution
turned opaque at 50 °C, indicating the micelle formation.
Results: The aldol reaction of 4-nitrobenzylaldehyde and cyclohexanone was catalyzed with the copolymer micelles, and
the product was obtained in good yield with excellent diastereo- and enantioselectivity. Both the yield and stereoselectivity
were superior to those obtained by using our previously developed proline-immobilized “broom”-type PNIPAAm-b-
PEG copolymer catalysts. The Michael reaction was also catalyzed by the “linear”-type PNIPAAm-b-PEG catalyst and
resulted in moderate yields with good stereoselectivity.
Conclusion: We have synthesized a series of “linear” thermoresponsive block copolymers on which L-proline moieties
were immobilized. The polymer catalyst formed micelles at 50 °C. The aldol reaction was catalyzed by the copolymer in
water with high diastereo- and enantioselectivity. The catalytic performance of the linear copolymer was superior to that
of the similar “broom”-type copolymer. The polymer catalyst also catalyzed the enantioselective Michael addition reaction.