四川大学余达刚团队报道了可见光光催化下三元C（sp³）-H键与CO₂的直接羧化反应——全碳四元羧酸的简易合成。相关研究成果于2024年10月7日发表在《美国化学会杂志》。

C-H键与CO₂的直接羧化是一种有吸引力的策略，可以合成具有高原子、台阶和氧化还原经济性的有价值的羧酸。尽管在这一领域取得了很大进展，但由于其固有的惰性和显著的空间位阻，叔C（sp³）-H键的催化羧化仍然具有挑战性。

该文中，研究人员报告了通过可见光光光氧化催化三元苄基C（sp³）-H键与CO₂的直接羧化。成功地以高产率获得了在药物化学中具有重要意义的各种全碳四元羧酸。这种直接羧化的特点是具有良好的官能团耐受性、广泛的底物范围和温和的操作条件。

此外，该方法能够高效快速地合成关键药物或生物活性分子，如碳正戊烷、焦糖芬和PRE-084（σ1受体激动剂），并利用靶羧酸的导向能力促进C（sp²）-H键的各种功能化，从而突出其实际应用。机理研究表明，碳负离子是与二氧化碳反应的关键中间体，是通过连续的光诱导电子转移过程，通过苄基自由基的单电子还原催化产生的。

附：英文原文

Title: Visible-Light Photoredox-Catalyzed Direct Carboxylation of Tertiary C(sp3)–H Bonds with CO2: Facile Synthesis of All-Carbon Quaternary Carboxylic Acids

Author: Yi Liu, Guan-Hua Xue, Zhen He, Jun-Ping Yue, Min Pan, Lei Song, Wei Zhang, Jian-Heng Ye, Da-Gang Yu

Issue&Volume: October 7, 2024

Abstract: Direct carboxylation of C–H bonds with CO2 represents an attractive strategy to synthesize valuable carboxylic acids with high atom, step, and redox economy. Although great progress has been achieved in this field, catalytic carboxylation of tertiary C(sp3)–H bonds still remains challenging due to their inherent inertness and significant steric hindrance. Herein, we report a direct carboxylation of tertiary benzylic C(sp3)–H bonds with CO2 via visible-light photoredox catalysis. Various all-carbon quaternary carboxylic acids, which are of significant importance in medicinal chemistry, are successfully obtained with high yields. This direct carboxylation is characterized by good functional group tolerance, broad substrate scope, and mild operational conditions. Furthermore, our methodology enables the efficient and rapid synthesis of key drug or bioactive molecules, such as carbetapentane, caramiphen, and PRE-084 (σ1 receptor agonist), and facilitates various functionalizations of C(sp2)–H bonds using the directing ability of target carboxylic acids, thus highlighting its practical applications. Mechanistic studies indicate that a carbanion, which serves as the key intermediate to react with CO2, is catalytically generated via a single electron reduction of a benzylic radical through a consecutive photoinduced electron transfer process.

DOI: 10.1021/jacs.4c09558

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c09558