Palladium-Catalyzed gem-Difluoroallylation Reaction between Aryltributyltin and Bromodifluoromethylated Alkenes

Abstract

A robust Stille gem-difluoroallylation of arylstannanes with 3-bromo-3,3-difluoropropenes has been established. The catalyst was found to exert critical effect on the reaction chemoselectivity. By using Pd­(OH)2/C as the catalyst, a series of 3-(hetero)­aryl/vinyl-3,3-difluoropropenes were obtained in high efficiency with α-substitution regioselectivity. The reaction has a broad substrate scope, and various substitution patterns were well tolerated in both substrates. Notably, the reaction can be easily extended to late-stage gem-difluoroallylation of many bioactive molecules with good chemoselectivity.

Visible light-mediated metal-free alkyl Suzuki–Miyaura coupling of alkyl halides and alkenylboronic acids/esters: a green method for the synthesis of allyl difluoride derivatives

“…Until now, various methods for the synthesis of allylic difluorides have been reported, including the transition metal-catalyzed C–H difluoroalkylation of alkenes, 5 C sp 2 –C sp 3 Suzuki–Miyaura coupling, 6 cross-coupling of difluoroalkylation and alkenyl halides, 7 decarboxylative difluoroalkylation of alkenes, 8 difluoroalkylation of alkynes 9 and others. 10 Among these, C sp 2 –C sp 3 Suzuki–Miyaura coupling is more attractive and has recently made great progress; 11 however, most of the reported examples require transition metal catalysts such as Pd, 12 Ni, 13 and Cu 14 complexes with designed ligands, which limit their application in the synthesis of drug-active molecules due to metal residue pitfalls (Scheme 1-1). In contrast, as a cheap, nontoxic, and environmentally friendly method to facilitate the assembly of biologically active compounds without metal residues, the metal-free C sp 2 –C sp 3 Suzuki–Miyaura coupling of sp 3 -hybridized carbon electrophiles has recently emerged as an attractive alternative in cross-coupling chemistry (Scheme 1-2).…”

Ruthenium-Catalyzed Ligand-Enabled Regiodivergent Difluoroallylation of Aryl C–H Bonds

“…Our group has previously developed a series of ruthenium-catalyzed ortho-or meta-selective C−H activations to build C−heteroatom bonds, 36−39 and we continue to be interested in ruthenium catalysis and the development of new difluoromethylation-related chemistry. 40,41 Herein we present a new method for regiodivergent difluoroallylation of arenes using ruthenium-catalyzed C−H bond activation (Figure 1d). 42−46 We initially investigated the reaction conditions for metaα,α-difluoroallyation (Supporting Information (SI) Table 1).…”

“…Although the use of palladium or manganese catalysts for γ-selective ortho -difluoroallylations has been established (Figure c, right), there has been no investigation into α-selective C–H difluoroallylation on both ortho and meta positions of arenes. Our group has previously developed a series of ruthenium-catalyzed ortho - or meta -selective C–H activations to build C–heteroatom bonds, − and we continue to be interested in ruthenium catalysis and the development of new difluoromethylation-related chemistry. , Herein we present a new method for regiodivergent difluoroallylation of arenes using ruthenium-catalyzed C–H bond activation (Figure d). − …”

Difluoromethylene insertion into fluoroalkyl copper complexes

“…1B). The synthetic methods of difluoromethylene compounds are relatively abundant, including the deoxyfluorination of ketones, 10 the nucleophilic transformation of difluoroenolates [11][12][13] and related nucleophiles, 14,15 regioselective difluoroallylation, [16][17][18][19][20] the addition of difluoroalkyl radical, [21][22][23] and the transfer of difluorocarbene. 24,25 The synthesis of tetrafluoroethylene bridged compounds has been achieved by the double deoxyfluorination of 1,2-diketone species; however, the reaction requires a large amount of corrosive fluorination reagents.…”