Trifluoromethylthiolation, Trifluoromethylation, and Arylation Reactions of Difluoro Enol Silyl Ethers

Abstract

This study reports a new application area of difluoro enol silyl ethers, which can be easily obtained from trifluoromethyl ketones. The main focus has been directed to the electrophilic fluoroalkylation and arylation methods. The trifluoromethylthiolation of difluoro enol silyl ethers can be used for the construction of a novel trifluoromethylthio-α,α-difluoroketone (−COCF 2 SCF 3 ) functionality. The −CF 2 SCF 3 moiety has interesting properties due to the electron-withdrawing, albeit lipophilic, character of the SCF 3 group, which can be combined with the high electrophilicity of the difluoroketone motif. The methodology could also be extended to difluoro homologation of the trifluoromethyl ketones using the Togni reagent. In addition, we presented a method for transition-metal-free arylation of difluoro enol silyl ethers based on hypervalent iodines.

Difluorinated Silyl Enol Ethers as Fluorine-Containing Building Blocks for the Synthesis of Organofluorine Compounds

“…为 拓 宽 二 氟 烯 醇 硅 醚 与 亲 电 试 剂 的 反 应 类 型 , Szabo 课题组 [32] 首次使用 N-三氟甲基硫代二苯磺酰亚胺 作为三氟甲基硫醇化试剂, 在 KF 为添加剂的作用下, 与二氟烯醇硅醚反应, 可以得到一系列新型的多氟烷基 化含硫化合物(Scheme 14A). 所引入的 SCF 3 基团是药 物分子中的核心结构单元之一, 利用其强吸电子特性和 高亲脂性可以显著改善目标分子的药物化学性质.…”

Decarboxylative arylation with diaryliodonium(iii) salts: alternative approach for catalyst-free difluoroenolate coupling to aryldifluoromethyl ketones

“…2b). 12,13 These methods require the use of organometallic species and transition metal catalysts, which increases costs and generates stoichiometric amounts of metallic byproducts containing zinc, boron, or silicon salts. Direct C–H bond functionalization of arenes (Fig.…”

Halotrifluoromethylation of 1,3-Enynes: Access to Tetrasubstituted Allenes

“…Thus, it is of great value to construct halogen-containing trifluoromethyl frameworks simultaneously through a one-pot procedure. By the complementary use of nucleophilic halide reagents and electrophilic CF 3 reagents, many elegant works have been well illustrated through a difunctionalization strategy that allows convenient and efficient access to the halogenated trifluoromethyl compounds. − In these reports, a variety of metal- or organocatalyzed systems were proven to be efficient for the halotrifluoromethylation, and their reactivity toward different multibond compounds, such as alkenes, alkynes, ,, and other unsaturated compounds, were investigated. In addition, for the terminal alkenes or (hetero)­arenes, a C­(sp 2 )–H trifluoromethylation may also occur .…”

“…On the basis of the previous observations and previous literature data, − a mechanism for the halotrifluoromethylation of 1,3-enynes has been proposed in Scheme . Initially, an electrophilic trifluoromethyl radical ( • CF 3 ) was generated from Togni’s reagent 2a via a single-electron-transfer (SET) caused by the copper­(II) complex with concomitant formation of copper­(III) species.…”

“…In conclusion, we have developed the first copper-mediated 1,4-halotrifluoromethylation of 1,3-enynes with an electrophilic trifluoromethylating reagent and a nucleophilic halide reagent (SOX 2 ), an approach that previously presented a formidable challenge. − Various halo- and CF 3 -containing tetrasubstituted allenes were formed with high yield and regioselectivity, which can be easily converted into some valuable molecules. This process is readily scaled up, and diverse transformations of 1,3-enynes are being pursued for the late-stage derivatization of biologically relevant compounds.…”