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通过铁介导的光催化单电子转移实现烯烃双(三氟甲基)羟甲基化反应合成烷基双(三氟甲基)甲醇

Synthesis of Alkyl Bis(trifluoromethyl)carbinols via Fe-LMCT-Enabled Hydrobis(trifluoromethyl)carbinolation of Alkenes.

作者信息

Guo Huaixuan, Lai Wenting, Ni Jie, Xu Peng

机构信息

Department of Chemistry, College of Sciences, Shanghai University, 99 Shangda Road, Shanghai 200444, P. R. China.

出版信息

Org Lett. 2024 Nov 8;26(44):9568-9573. doi: 10.1021/acs.orglett.4c03609. Epub 2024 Oct 30.

Abstract

Bis(trifluoromethyl)carbinols are valuable pharmacophores, yet their synthesis is challenging, largely due to a scarcity of safe and effective bis(trifluoromethyl)carbinolation reagents. Here, we realized the hydrobis(trifluoromethyl)carbinolation of alkenes, utilizing stable and readily accessible 2,2-bis(trifluoromethyl)glycolic acid as a source of both the bis(trifluoromethyl)carbinol unit and a hydrogen atom. This process leverages a photoinduced Fe-LMCT-enabled radical decarboxylation process that generates a key bis(trifluoromethyl)carbinol radical intermediate. Our mild protocol facilitates the synthesis of a diverse range of alkyl bis(trifluoromethyl)carbinols, including structurally complex molecules with pharmaceutical relevance.

摘要

双(三氟甲基)甲醇是有价值的药效基团,但其合成具有挑战性,主要原因是缺乏安全有效的双(三氟甲基)羟甲基化试剂。在此,我们利用稳定且易于获得的2,2-双(三氟甲基)乙醇酸作为双(三氟甲基)甲醇单元和氢原子的来源,实现了烯烃的氢双(三氟甲基)羟甲基化反应。该过程利用了光诱导的铁-配体中心电荷转移引发的自由基脱羧过程,生成关键的双(三氟甲基)甲醇自由基中间体。我们的温和方案有助于合成多种烷基双(三氟甲基)甲醇,包括具有药物相关性的结构复杂分子。

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