美国斯克里普斯研究所Yu, Jin-Quan团队报道了铜催化的C（sp³）H键脱氢或内酯化。相关研究成果发表在2024年3月28日出版的国际学术期刊《自然》。

已知细胞色素P450酶通过在羟基化和去饱和途径之间，分配的自由基中间体催化脂肪酸双峰氧化。开发用于远程CH功能化的类似催化体系仍然是一个重大挑战。

该文中，研究人员报道了通过γ-脂族CH键的自由基提取，Cu（I）催化合成常见N-甲氧基酰胺的双峰脱氢/内酯化反应的发展。通过改变反应条件也证明了从脱氢转变为内酯化的可行性。使用易得的酰胺作为自由基前体和内部氧化剂，能够开发以甲醇作为唯一副产物的氧化还原中性CH官能化反应。

使用负载低至0.5mol%的Cu（I）催化剂的这些CH官能化反应，已经应用于包括药物分子和天然产物的广泛的脂肪酸多样化。该催化体系具有广泛的氧化敏感功能和非凡的兼容性，证明了使用简单的酰胺底物作为温和的内氧化剂的独特优势。

附：英文原文

Title: Copper-catalyzed dehydrogenation or lactonization of C(sp3)H bonds

Author: Zhou, Shupeng, Zhang, Zi-Jun, Yu, Jin-Quan

Issue&Volume: 2024-03-28

Abstract: Cytochrome P450 enzymes are known to catalyze bimodal oxidation of aliphatic acids via radical intermediates, which partition between pathways of hydroxylation and desaturation5,6. Developing analogous catalytic systems for remote CH functionalization remains a significant challenge14,15,16. Here we report the development of Cu(I)-catalyzed bimodal dehydrogenation/lactonization reactions of synthetically common N-methoxyamides via radical abstractions of the γ-aliphatic CH bonds. The feasibility of switching from dehydrogenation to lactonization has also been demonstrated by altering reaction conditions. The use of a readily available amide as both radical precursor and internal oxidant allowed for the development of a redox-neutral CH functionalization reactions with methanol as the sole side product. These CH functionalization reactions using Cu(I) catalyst of loading as low as 0.5 mol% have been 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 simple amide substrate as the mild internal oxidant.

DOI: 10.1038/s41586-024-07341-z

Source: https://www.nature.com/articles/s41586-024-07341-z