Copper-catalysed dehydrogenation or lactonization of C(sp3)-H bonds

• 成果类型: Article
• 署名作者: Zhou, Shupeng; Zhang, Zi-Jun; Yu, Jin-Quan
• 署名单位: Scripps Research Institute
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5067
• DOI: 10.1038/s41586-024-07341-z
• 发表日期: 2024-05-09
• 页码: 363-+
• 关键词: c-h bonds; alkyl radicals; oxidation; hydroxylation; functionalization; desaturation; mechanisms; chemistry; enzymes

摘要

Cytochrome P450 enzymes are known to catalyse bimodal oxidation of aliphatic acids via radical intermediates, which partition between pathways of hydroxylation and desaturation(1,2). Developing analogous catalytic systems for remote C-H functionalization remains a significant challenge(3-5). Here, we report the development of Cu(I)-catalysed bimodal dehydrogenation/lactonization reactions of synthetically common N-methoxyamides through radical abstractions of the gamma-aliphatic C-H bonds. The feasibility of switching from dehydrogenation to lactonization is also demonstrated by altering reaction conditions. The use of a readily available amide as both radical precursor and internal oxidant allows for the development of redox-neutral C-H functionalization reactions with methanol as the sole side product. These C-H functionalization reactions using a Cu(I) catalyst with loading as low as 0.5mol.% is applied to the diversification of a wide range of aliphatic acids including drug molecules and natural products. The exceptional compatibility of this catalytic system with a wide range of oxidatively sensitive functionality demonstrates the unique advantage of using a simple amide substrate as a mild internal oxidant.