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.

金属催化的交叉偶联是有机合成的支柱，广泛用于形成 C-C 键，特别是在不饱和支架的生产中¹。然而，使用天然sp ³杂化官能团（如醇）的烷基交叉偶联仍然相对不发达²。特别是，一种稳健且通用的醇直接脱氧偶联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，最值得注意的是强 C-O 键的原位裂解³，但将允许使用大量可商购的、结构多样的醇作为偶联伙伴⁴. 我们在此报告了一种基于金属光氧化还原的交叉偶联平台，其中游离醇被 N-杂环卡宾盐原位活化，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，最重要的是，能够适应各种伯醇、仲醇和叔醇以及药学相关的芳基和杂芳基溴化物和氯化物。这种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。该技术代表了原位醇活化与过渡金属催化相结合的一般策略。