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Enantioselective hydrogenation of \u03b2-amino ketones provides a straightforward and powerful tool for the synthesis of chiral \u03b3-amino alcohols, but the asymmetric transformation is synthetically challenging. Here, a series of tridentate ferrocene-based phosphine ligands bearing modular and tunable unsymmetrical vicinal diamine scaffolds were designed, synthesized, and evaluated in the iridium-catalyzed asymmetric hydrogenation of \u03b2-amino ketones. The system was greatly effective to substrates with flexible structure and functionality, and diverse \u03b2-tertiary-amino ketones and \u03b2-secondary-amino ketones were hydrogenated smoothly. The excellent reactivities and enantioselectivities were achieved in the asymmetric delivery of various chiral \u03b3-amino alcohols with up to 99% yields, &gt;99% ee values, and turnover number (TON) of 48,500. The gram-scale reactions with low catalyst loading showed the potential application in industrial synthesis of chiral drugs, such as (<jats:italic>S<\/jats:italic>)-duloxetine, (<jats:italic>R<\/jats:italic>)-fluoxetine, and (<jats:italic>R<\/jats:italic>)-atomoxetine.<\/jats:p>","DOI":"10.1038\/s42004-022-00678-4","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T10:05:28Z","timestamp":1652954728000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Iridium-catalyzed enantioselective synthesis of chiral \u03b3-amino alcohols and intermediates of (S)-duloxetine, (R)-fluoxetine, and (R)-atomoxetine"],"prefix":"10.1038","volume":"5","author":[{"given":"Chengyu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyue","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1171-2308","authenticated-orcid":false,"given":"Ruihua","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-6807","authenticated-orcid":false,"given":"Jinxing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"678_CR1","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1021\/jm00402a027","volume":"31","author":"DW Robertson","year":"1988","unstructured":"Robertson, D. 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