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In doing so, the substrate breadth for this emerging methodology has been significantly broadened. The method is also no longer beholden to proline-based catalyst templates, e.g., commercially available O-t-Bu-L-threonine is advantageous for acyclic ketones. The key insight was to exploit water-based mediums under conventional (in-water) and non-conventional (deep eutectic solvents) conditions. With few exceptions, high aldol-to-Knoevenagel chemoselectivity (&gt;10:1) and good product profiles (yield, dr, and ee) were observed, but only in DESs (deep eutectic solvents) in conjunction with ball milling did short reaction times occur.<\/jats:p>","DOI":"10.3390\/molecules29010004","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T04:18:37Z","timestamp":1702959517000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Enantioselective Catalytic Aldol Reactions in the Presence of Knoevenagel Nucleophiles: A Chemoselective Switch Optimized in Deep Eutectic Solvents Using Mechanochemistry"],"prefix":"10.3390","volume":"29","author":[{"given":"Hanaa","family":"Al Beiruty","sequence":"first","affiliation":[{"name":"School of Science, Constructor University, Campus Ring 1, 28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiia-Stefaniia","family":"Zhylinska","sequence":"additional","affiliation":[{"name":"School of Science, Constructor University, Campus Ring 1, 28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nino","family":"Kutateladze","sequence":"additional","affiliation":[{"name":"School of Science, Constructor University, Campus Ring 1, 28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9479-1186","authenticated-orcid":false,"given":"Hayley Kay Tinn","family":"Cheong","sequence":"additional","affiliation":[{"name":"School of Science, Constructor University, Campus Ring 1, 28759 Bremen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1605-2292","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"\u00d1\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Organic Synthesis (ISO), University of Alicante, P.O. 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