近日，浙江工业大学李坚军团队研究了利用水作为可持续氧源的非活化脂肪族C-H键的光电催化氧化。该项研究成果发表在2025年11月3日出版的《美国化学会志》上。

脂肪族C-H键的氧化是合成化学中的一个关键转变，因为它将无处不在的烷烃原料转化为有价值的酮和醇。然而，选择性地实现这种转变仍然是一个巨大的障碍，因为C-H键的固有惰性阻碍了它们的活化，而不同位点之间键离解能的细微差异使得实现高区域选择性变得困难。

研究组提出了一种使用水作为氧源的分子内引导策略，实现了N-烷基磺酰胺的电子光化学δ-C（sp³）-H氧化。这种无氧化剂的方案适应了各种底物上的一级、二级和三级C-H键，具有优异的官能团耐受性，使其能够成功应用于克级合成以及天然产物和药物衍生物的后期功能化。机理研究支持通过氧化自由基极性交叉进行的顺序氧化途径，其中初始羟基化事件之后是快速的后续氧化，以提供最终的酮产物。

附：英文原文

Title: Electrophotocatalytic Oxygenation of Unactivated Aliphatic C–H Bonds Using Water as a Sustainable Oxygen Source

Author: Chaodong Wang, Luwei Tong, Chenxi Gu, Zhi Chen, Jie Sun, Jianjun Li

Issue&Volume: November 3, 2025

Abstract: The oxygenation of aliphatic C–H bonds is a crucial transformation in synthetic chemistry, as it transforms ubiquitous alkane feedstocks into valuable ketones and alcohols. However, achieving this transformation selectively remains a formidable hurdle since the inherent inertness of C–H bonds hinders their activation, while the subtle differences in bond dissociation energies among various sites make achieving high regioselectivity difficult. Herein, we present an electrophotochemical δ-C(sp3)–H oxygenation of N-alkylsulfonamides enabled by an intramolecular guidance strategy using water as the oxygen source. This oxidant-free protocol accommodates primary, secondary, and tertiary C–H bonds across a diverse range of substrates with excellent functional group tolerance, enabling its successful application to gram-scale synthesis and the late-stage functionalization of natural products and drug derivatives. Mechanistic studies support a sequential oxidation pathway proceeding via an oxidative radical-polar crossover, wherein an initial hydroxylation event is followed by a rapid, subsequent oxidation to furnish the final ketone product.

DOI: 10.1021/jacs.5c12000

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c12000