{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:29:03Z","timestamp":1790958543272,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Research Foundation (NRF) and funded by the Korean government (MSIT)","award":["2021R1A6A3A01087948"],"award-info":[{"award-number":["2021R1A6A3A01087948"]}]},{"name":"the Bio &amp; Medical Technology Development Program of the NRF and funded by the Korean government (MSIT)","award":["2021M3A9G1097744"],"award-info":[{"award-number":["2021M3A9G1097744"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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, \u226597% 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.<\/jats:p>","DOI":"10.3390\/molecules27092759","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T02:14:39Z","timestamp":1650939279000},"page":"2759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Enantioselective Organocatalyzed Michael Addition of Isobutyraldehyde to Maleimides in Aqueous Media"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9861-6521","authenticated-orcid":false,"given":"Jae Ho","family":"Shim","sequence":"first","affiliation":[{"name":"Department of Anatomy, College of Medicine, Korea University, 73, Goryeodae-ro, Seongbuk-gu, Seoul 02481, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok Hyun","family":"Cheun","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Korea University, 145 Anam-ro, Seoul 02481, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Korea University, 73, Goryeodae-ro, Seongbuk-gu, Seoul 02481, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deok-Chan","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Korea University, 145 Anam-ro, Seoul 02481, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nature07367","article-title":"The advent and development of organocatalysis","volume":"455","author":"MacMillan","year":"2008","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.1002\/anie.200400650","article-title":"In the golden age of organocatalysis","volume":"43","author":"Dalko","year":"2004","journal-title":"Angew. 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