手性α-立体异构氧杂环丁醇和氮杂环丁醇 烯丙基乙酸酯的醇介导还原偶联：对称酮加成中的对映异位π-面选择
Chiral α-Stereogenic Oxetanols and Azetidinols Alcohol-Mediated Reductive Coupling of Allylic Acetates: Enantiotopic π-Facial Selection in Symmetric Ketone Addition.
作者信息
Stafford Nicholas P, Cheng Melinda J, Dinh Duong Nguyen, Verboom Katherine L, Krische Michael J
机构信息
University of Texas at Austin, Department of Chemistry, 105 E 24th St. Austin, TX 78712, USA.
出版信息
ACS Catal. 2022 May 20;12(10):6172-6179. doi: 10.1021/acscatal.2c01647. Epub 2022 May 9.
Abstract
Iridium-tol-BINAP-catalyzed reductive coupling of allylic acetates with oxetanones and azetidinones mediated by 2-propanol provides chiral α-stereogenic oxetanols and azetidinols. As illustrated in 50 examples, complex, nitrogen-rich substituents that incorporate the top 10 -heterocycles found in FDA-approved drugs are tolerated. In addition to 2-propanol-mediated reductive couplings, oxetanols and azetidinols may serve dually as reductant and ketone proelectrophiles in redox-neutral C-C couplings via hydrogen auto-transfer, as demonstrated by the conversion of - and - to adducts and , respectively. The present method delivers hitherto inaccessible chiral oxetanols and azetidinols, which are important bioisosteres.
摘要
铱-手性联萘膦催化的烯丙基乙酸酯与氧杂环丁酮和氮杂环丁酮在异丙醇介导下的还原偶联反应可提供手性α-立体异构氧杂环丁醇和氮杂环丁醇。如50个实例所示，该反应能够耐受包含FDA批准药物中排名前十的杂环的复杂富氮取代基。除了异丙醇介导的还原偶联反应外，氧杂环丁醇和氮杂环丁醇还可通过氢自动转移在氧化还原中性的碳-碳偶联反应中同时作为还原剂和酮前亲电试剂，分别将-和-转化为加合物和即可证明这一点。本方法可提供迄今难以获得的手性氧杂环丁醇和氮杂环丁醇，它们是重要的生物电子等排体。
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