Thiourea was introduced into (R,R)-1,2-diphenylethylenediamine as an organocatalyst to promote the reaction between isobutyraldehydes and maleimides. Enantioselective Michael addition reaction was carried out as an eco-friendly method using water as the solvent. As a result of the reaction between isobutyraldehyde and maleimide, ≥97% yield and 99% enantioselectivity were obtained at a low catalyst loading of 0.01 mol%. The solvent effect can be explained by theoretical calculations that indicate the participation of a transition state, in which the CF3 substituent of the catalyst is a hydrogen bond activated by the surrounding water molecules. This discovery enabled the use of low catalyst loading in the organic reactions of chiral substances for pharmaceutical applications. Furthermore, a solvent effect for Michael reaction of the organocatalysts was proposed, and the organic reaction mechanisms were determined through quantum calculations.
Bibliographical noteFunding Information:
Funding: This study was supported by the National Research Foundation (NRF) and funded by the Korean government (MSIT) (2021R1A6A3A01087948); by the Bio & Medical Technology Development Program of the NRF and funded by the Korean government (MSIT) (2021M3A9G1097744); and by a Korea University grant.
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- Michael addition
ASJC Scopus subject areas
- Analytical Chemistry
- Chemistry (miscellaneous)
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery
- Physical and Theoretical Chemistry
- Organic Chemistry