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金属催化光还原策略使醇脱氧芳基化
作者:小柯机器人 发布时间:2021/9/4 20:25:31

美国普林斯顿大学MacMillan, David W. C.团队报道了金属催化光还原策略使醇脱氧芳基化。相关研究成果于2021年8月31日发表在国际顶尖学术期刊《自然》。

金属催化交叉偶联是有机合成的主要方法,广泛用于C-C键的形成,特别是在不饱和支架的生产中。然而,使用天然sp3杂化官能团(如醇)的烷基交叉偶联仍然相对不足。特别是,一种用于醇的直接脱氧偶联的稳健且通用的方法将对有机合成领域产生重大影响。游离醇直接脱氧交叉偶联的一般方法必须克服几个挑战,最显著的是强C–O键的原位裂解,同时将允许获得大量商用、结构多样的醇作为偶联伙伴。

研究人员在该文中报道了一种基于metallaphotoredox反应的交叉偶联平台,其中自由醇被N-杂环卡宾盐原位活化,用于与芳基卤化物偶联伙伴形成碳-碳键。该方法温和、稳健、选择性好,最重要的是,能够适应广泛的伯、仲、叔醇以及医药相关的芳基和杂芳基溴化物和氯化物。该转变的力量已经在许多复杂的环境中得到证明,包括紫杉醇的后期功能化和抗糖尿病药物Januvia的模块化合成。该技术代表了原位乙醇活化与过渡金属催化相结合的通用策略。

附:英文原文

Title: Metallaphotoredox-enabled deoxygenative arylation of alcohols

Author: Dong, Zhe, MacMillan, David W. C.

Issue&Volume: 2021-08-31

Abstract: Metal-catalysed cross-couplings are a mainstay of organic synthesis and are widely used for the formation of C-C bonds, particularly in the production of unsaturated scaffolds1. However, alkyl cross-couplings using native sp3-hybridized functional groups such as alcohols remain relatively underdeveloped2. In particular, a robust and general method for the direct deoxygenative coupling of alcohols would have major implications for the field of organic synthesis. A general method for the direct deoxygenative cross-coupling of free alcohols must overcome several challenges, most notably the in situ cleavage of strong C–O bonds3, but would allow access to the vast collection of commercially available, structurally-diverse alcohols as coupling partners4. We report herein a metallaphotoredox-based cross-coupling platform in which free alcohols are activated in situ by N-heterocyclic carbene salts for carbon-carbon bond formation with aryl halide coupling partners. This method is mild, robust, selective, and most importantly, capable of accommodating a wide range of primary, secondary, and tertiary alcohols as well as pharmaceutically-relevant aryl and heteroaryl bromides and chlorides. The power of the transformation has been demonstrated in a number of complex settings, including the late-stage functionalization of Taxol and a modular synthesis of Januvia, an antidiabetic medication. This technology represents a general strategy for the merger of in situ alcohol activation with transition metal catalysis.

DOI: 10.1038/s41586-021-03920-6

Source: https://www.nature.com/articles/s41586-021-03920-6

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:42.778
官方网址:http://www.nature.com/