Synthesis of difluoromethyl carbinols from the Friedel–Crafts reaction of electron-rich arenes with difluorovinyl arylsulfonates

Abstract

α,α-Difluoromethyl carbinols are important structural motifs in many therapeutic agents and functional materials. Herein, we developed a sustainable and efficient method for the synthesis of a series of α,α-difluoromethyl carbinols...

Synthesis of Difluoromethylated Carbinols via a HFIP-Promoted Hydroxydifluoromethylation of Aniline, Indole, and Pyrrole Derivatives with Difluoroacetaldehyde Ethyl Hemiacetal

“…). 14 The crude products were purified by column chromatography with petroleum ether/ethyl acetate (30/1 to 10/1, v/v) as eluent to give compound 3e (yellow oily liquid, 42.9 mg, 0.18 mmol, 89% yield). 1 H NMR (400 MHz, CDCl 3 ): δ 7.25−7.21 (m, 2H), 6.92−6.88 (m, 2H), 5.72 (td, J = 56.2, 4.8 Hz, 1H), 4.66 (td, J = 10.3, 4.8 Hz, 1H), 3.17− 3.14 (m, 4H), 2.72 (s, 1H), 1.72−1.66 (m, 4H), 1.60−1.54 (m, 2H).…”

“…19 2,2-Difluoro-1-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)ethan-1-ol (3f). 14 The crude products were purified by column chromatography with petroleum ether/ethyl acetate (30/1 to 10/1, v/v) as eluent to give compound 3f (white solid, 39.9 mg, 0.16 mmol, 79% yield). Mp: 117−119 °C.…”

“…13 Very recently, Wu et al reported a new method for the synthesis of difluoromethylated carbinols from electron-rich arenes with difluorovinyl arysulfonates by Friedel−Crafts reaction (Scheme 1b). 14 Despite the impressive progress, some of them suffer from the multistep procedure, harsh reaction conditions, and expensive catalysts, which greatly restrict their applications. Thus, a milder and more convenient methodology for the construction of the difluoromethylated carbinol scaffold is needed.…”

“…For example, Liu and co-workers developed a metal- and ligand-free decarboxylative difluoromethylation reaction of the nucleophilic PhSO 2 CF 2 COOK with aldehyde to access difluoromethylated carbinol, and then, the difluoromethylated carbinol was obtained after cleavage of the C–S bond (Scheme a) . Very recently, Wu et al reported a new method for the synthesis of difluoromethylated carbinols from electron-rich arenes with difluorovinyl arysulfonates by Friedel–Crafts reaction (Scheme b) . Despite the impressive progress, some of them suffer from the multistep procedure, harsh reaction conditions, and expensive catalysts, which greatly restrict their applications.…”

Rh(iii)-catalyzed redox-neutral C–H alkenylation of benzamides with gem-difluorohomoallylic silyl ethers via β-H elimination

“…6 Environmentally benign and cost-effective approaches inspire researchers to develop new, selective methods, in particular those that use simple and readily available fluorinated building blocks. 7,8…”