Fu Hong, Wang Zuo-Shuai, Li Si-Jia, Zhu Lin-Yuan, Wang Xiao-Jian, Wang Hong-Chen, Han Bing
State Key Laboratory of Applied Organic Chemistry (SKLAOC), College of Chemistry and Chemical Engineering, Lanzhou University 222 South Tianshui Road Lanzhou 730000 People's Republic of China
Chem Sci. 2025 Feb 19;16(14):5849-5856. doi: 10.1039/d4sc08607d. eCollection 2025 Apr 2.
A transition-metal-free protocol for the unsymmetrical radical 1,3-difunctionalization of alkenes has been established for the first time in the form of 1,3-difluoroalkylcarboxylation by a photocatalytic radical three-component reaction of allyl formates, trifluoroacetanilides, and cesium formate. This reaction employs formate as the carboxylating reagent and trifluoroacetanilide as the difluoroalkylating reagent C-F bond activation. As a result, a series of previously inaccessible unsymmetrical difluorinated adipic acid derivatives can be easily and efficient prepared. Mechanism studies reveal that triple kinetic-controlled radical self-ordering is the key to this unique reaction. This radical sorting involves the fast initiation of a CO radical anion and its chemoselective addition and reduction, followed by the slow generation of a fluoroalkyl radical and its chemo-/regioselective addition. Notably, this strategy is also suitable for the 1,3-difluoroalkylcarboxylation of unsymmetrical and cyclic alkenes through diastereoselectively constructing two or three consecutive stereocenters.
首次通过烯丙基甲酸酯、三氟乙酰苯胺和甲酸钾的光催化自由基三组分反应，以1,3-二氟烷基羧化的形式建立了一种无过渡金属的烯烃不对称自由基1,3-双官能团化方法。该反应使用甲酸盐作为羧化试剂，三氟乙酰苯胺作为二氟烷基化试剂进行C-F键活化。结果，可以轻松高效地制备一系列以前无法获得的不对称二氟化己二酸衍生物。机理研究表明，三重动力学控制的自由基自排序是这一独特反应的关键。这种自由基排序涉及CO自由基阴离子的快速引发及其化学选择性加成和还原，随后是氟烷基自由基的缓慢生成及其化学/区域选择性加成。值得注意的是，该策略还适用于通过非对映选择性构建两个或三个连续的立体中心，对不对称和环状烯烃进行1,3-二氟烷基羧化反应。
