Stache Erin E, Ertel Alyssa B, Tomislav Rovis, Doyle Abigail G
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
ACS Catal. 2018 Dec 7;8(12):11134-11139. doi: 10.1021/acscatal.8b03592. Epub 2018 Oct 18.
Despite the prevalence of alcohols and carboxylic acids as functional groups in organic molecules and the potential to serve as radical precursors, C-O bonds remain difficult to activate. We report a synthetic strategy for direct access to both alkyl and acyl radicals from these ubiquitous functional groups via photoredox catalysis. This method exploits the unique reactivity of phosphoranyl radicals, generated from a polar/SET crossover between a phosphine radical cation and an oxygen-centered nucleophile. We show the desired reactivity in the reduction of benzylic alcohols to the corresponding benzyl radicals with terminal H atom trapping to afford the deoxygenated products. Using the same method, we demonstrate access to synthetically versatile acyl radicals, which enables the reduction of aromatic and aliphatic carboxylic acids to the corresponding aldehydes with exceptional chemoselectivity. This protocol also transforms carboxylic acids to heterocycles and cyclic ketones via intramolecular acyl radical cyclizations to forge C-O, C-N, and C-C bonds in a single step.
尽管醇类和羧酸类作为有机分子中的官能团普遍存在，并且有潜力作为自由基前体，但碳 - 氧键仍然难以活化。我们报道了一种通过光氧化还原催化从这些普遍存在的官能团直接获得烷基和酰基自由基的合成策略。该方法利用了由膦自由基阳离子与以氧为中心的亲核试剂之间的极性/单电子转移交叉产生的磷酰基自由基的独特反应性。我们展示了在将苄醇还原为相应的苄基自由基并通过末端氢原子捕获得到脱氧产物方面所需的反应性。使用相同的方法，我们证明了可以获得具有合成通用性的酰基自由基，这使得能够以优异的化学选择性将芳香族和脂肪族羧酸还原为相应的醛。该方案还通过分子内酰基自由基环化将羧酸转化为杂环和环状酮，从而在一步中形成碳 - 氧键、碳 - 氮键和碳 - 碳键。
