配体促进的掩蔽脂肪族醇的β-亚甲基 C(sp )-H 芳基化反应。
Ligand-Enabled β-Methylene C(sp )-H Arylation of Masked Aliphatic Alcohols.
机构信息
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA, 02142, USA.
出版信息
Angew Chem Int Ed Engl. 2020 May 11;59(20):7783-7787. doi: 10.1002/anie.202000632. Epub 2020 Mar 11.
Abstract
Despite recent advances, reactivity and site-selectivity remain significant obstacles for the practical application of C(sp )-H bond functionalization methods. Here, we describe a system that combines a salicylic-aldehyde-derived L,X-type directing group with an electron-deficient 2-pyridone ligand to enable the β-methylene C(sp )-H arylation of aliphatic alcohols, which has not been possible previously. Notably, this protocol is compatible with heterocycles embedded in both alcohol substrates and aryl coupling partners. A site- and stereo-specific annulation of dihydrocholesterol and the synthesis of a key intermediate of englitazone illustrate the practicality of this method.
摘要
尽管最近取得了一些进展，但反应性和位点选择性仍然是 C(sp )-H 键功能化方法实际应用的重大障碍。在这里，我们描述了一种系统，该系统将水杨酸衍生的 L，X 型导向基团与缺电子的 2-吡啶酮配体结合使用，从而实现了以前不可能的脂肪族醇的β-亚甲基 C(sp )-H 芳基化。值得注意的是，该方案与醇底物和芳基偶联物中嵌入的杂环均兼容。二氢胆固醇的位点和立体特异性环化以及恩格列酮关键中间体的合成说明了该方法的实用性。
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