Giri Rahul, Zhilin Egor, Katayev Dmitry
Department of Chemistry, Biochemistry, and Pharmaceutical Sciences, University of Bern Freiestrasse 3 3012 Bern Switzerland
Chem Sci. 2024 Jun 6;15(27):10659-10667. doi: 10.1039/d4sc01084a. eCollection 2024 Jul 10.
Herein we present our studies on the solvent-controlled difunctionalization of alkenes utilizing chlorodifluoroacetic acid (CDFA) and α-halo carboxylic acids for the synthesis of γ-lactones, γ-lactams and α,α-difluoroesters. Mechanistic insights revealed that photocatalytic reductive mesolytic cleavage of the C-X bond delivers elusive α-carboxyl alkyl radicals. In the presence of an olefin molecule, this species acts as a unique bifunctional intermediate allowing for stipulated formation of C-O, C-N and C-H bonds on Giese-type adducts single electron transfer (SET) or hydrogen atom transfer (HAT) events. These protocols exhibit great efficiency across a broad spectrum of readily available α-halo carboxylic acids and are amenable to scalability in both batch and flow. To demonstrate the versatility of this concept, the synthesis of (±)-boivinianin A, its fluorinated analog and eupomatilone-6 natural products was successfully accomplished.
在此，我们展示了我们利用氯二氟乙酸（CDFA）和α-卤代羧酸对烯烃进行溶剂控制的双官能化反应，以合成γ-内酯、γ-内酰胺和α,α-二氟酯的研究。机理研究表明，光催化还原C-X键的中裂产生难以捉摸的α-羧基烷基自由基。在烯烃分子存在下，该物种作为一种独特的双官能中间体，允许在吉斯型加合物上通过单电子转移（SET）或氢原子转移（HAT）事件规定形成C-O、C-N和C-H键。这些方案在各种易于获得的α-卤代羧酸中都表现出很高的效率，并且适用于批量和连续流的放大生产。为了证明这一概念的通用性，成功完成了（±）-波维宁宁A及其氟化类似物和优巴替隆-6天然产物的合成。
