Enantioselective Organocatalyzed Michael Addition of Isobutyraldehyde to Maleimides in Aqueous Media |
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Authors: | Jae Ho Shim Seok Hyun Cheun Hyeon Soo Kim Deok-Chan Ha |
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Institution: | 1.Department of Anatomy, College of Medicine, Korea University, 73, Goryeodae-ro, Seongbuk-gu, Seoul 02481, Korea;2.Department of Chemistry, College of Science, Korea University, 145 Anam-ro, Seoul 02481, Korea; (S.H.C.); (D.-C.H.) |
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Abstract: | 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. |
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Keywords: | organocatalyst enantioselectivity Michael addition aldehydes succinimides spironolactone |
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