Extension to the SCF ₂ H , SCH ₂ F , and SCF ₂ R Motifs ( R = PO ( OEt ) ₂

Abstract

In this chapter, the recent and most significant progress made for the access to SCF2H, SCH2F, SCF2PO(OEt)2, SCF2COR, and SRf will be highlighted. The SCF2H MotifOver the last years, a strong interest was paid to the SCF2H group. Indeed, due to its unique properties such as a its lipophilicity, its H-bonding ability [4] and due to the presence of a more acidic proton compared with the one in the CF2H group, the development of new approaches for its introduction onto various classes of compounds was reported. Two main strategies were depicted, namely 1) the difluoromethylation of sulfur-containing molecules and 2) the direct C-SCF2H bond construction. In this section will be reported the most relevant advances made since 2016 [5]. Construction of the SCF2H MoietyDue to the importance of the SCF2H group, various strategies were elaborated to build up a S-CF2H bond. Until 2016, the use of difluorocarbene precursors was the main approach. Alternatives based on electrophilic and nucleophilic reagents or CF2H radical precursors were promising, although still in their infancy. A summary of the main reagents used in these transformations is depicted in the Scheme 3.6-1 [5]. Scheme 3.6-1 State of the art: reagents used for the difluoromethylation of sulfur-containing molecules until 2016.In this section, will be described the recent advances made since 2016 to construct a S-CF2H bond.In 2017, the group of Fu developed a methodology for the difluoromethylation of thiophenols under visible light photocatalysis [6]. Using the readily available difluorobromoacetic acid as a difluorocarbene precursor and an iridium complex as photocatalyst, a panel of thiophenols bearing halogens, ester, nitro as functional groups was functionalized in moderate to high yields (Scheme 3.6-2a). Note that even the difluoromethylation of 2-pyridinethiol was smoothly achieved . Scheme 3.6-2 Difluoromethylation of thiophenols under visible light photocatalysis.Another difluorocarbene precursor, namely the diethyl bromodifluoromethylphosphonate, was also used in combination with thiourea as the sulfur source [7]. With this system, Yi and coworkers successfully functionalized in a one-pot three-step sequence, a panel of heteroaromatic compounds (indoles, pyrroles) and electron-rich arenes (Scheme 3.6-3).Scheme 3.6-3 Difluoromethylation of heteroaromatic compounds and electron-rich arenes using diethyl bromodifluoromethylphosphonate and thiourea.

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

“…Despite these advances, synthetic challenges still need to be overcome. These synthetic tools are so far still restricted to some fluorinated moieties and extension to other high valueadded fluorinated residues [131,136,[193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208] is of high importance. Besides, in comparison with the functionalization of C(sp 2 ) centers on aromatic and vinylic derivatives, transitionmetal-catalyzed functionalization of C(sp 3 )-H bonds remains largely underexplored to date.…”

“…More recently, researchers became interested in the synthesis of molecules substituted with original and functionalized fluorinated moieties such as SCF 2 FG [128][129][130][131][132][133][134][135][136] (FG = functional group). In sharp contrast with the trifluoromethylthiolation reaction, only a handful of reports dealt with the incorporation of such high value-added fluorinated moieties onto C(sp 2 ) centers by transition-metal-catalyzed C-H bond activation.…”