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Current Organocatalysis


ISSN (Print): 2213-3372
ISSN (Online): 2213-3380

Asymmetric Aldol and Michael Reactions in Water Using Organocatalysts Immobilized on a Thermoresponsive “Linear” Block Copolymer

Author(s): Noriyuki Suzuki, Ryuji Akebi, Takahiro Inoue, Masahiro Rikukawa and Yoshiro Masuyama

Volume 3, Issue 3, 2016

Page: [306 - 314] Pages: 9

DOI: 10.2174/2213337203666160304194141


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.

Keywords: L-proline, organocatalyst, polymer micelle, reaction in water, thermoresponsive polymer, N-isopropyl acrylamide.

Graphical Abstract

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