Two-Step Synthesis of 2-Trifluoromethylated and 2-Difluoromethylated Benzoheteroles Starting from HFO-1224yd(Z) and HFO-1233yd(Z)

Abstract

An efficient two-step method for synthesizing 2-(trifluoromethyl)-and 2-(difluoromethyl)benzoheteroles bearing various substituents was developed. Commercially available HFO-1224yd(Z) or HFO-1233yd(Z) underwent the Suzuki−Miyaura coupling with arylboronic acids (acid esters) bearing a nucleophilic moiety at the ortho position to yield the corresponding β-fluoroβ-(trifluoromethyl)or β-fluoro-β-(difluoromethyl)styrenes, respectively. Treatment of the obtained styrenes with potassium phosphate induced nucleophilic 5-endo-trig cyclization to provide the corresponding 2-trifluoromethylated or 2-difluoromethylated indoles and benzofurans, as well as benzothiophenes.Letter pubs.acs.org/OrgLett

Recent advances in the synthesis of trifluoromethyl-containing heterocyclic compounds via trifluoromethyl building blocks

“…In 2022, Ichikawa and co-workers 32 introduced a two-step approach utilizing readily accessible HFO-1224yd(Z) or HFO-1233yd(Z) as starting materials, providing an efficient entry to the corresponding 2-(trifluoromethyl)-and 2-(difluoromethyl)benzoheteroles with different substituents (Scheme 15). The HFOs were used in a Suzuki-Miyaura coupling reaction with arylboronic acids (acid esters) containing a nucleophilic group at the ortho-position to produce β-fluoroβ-(trifluoromethyl)or β-fluoro-β-(difluoromethyl)styrenes.…”

C–H and C–F bond activation of fluorinated propenes at Rh: enabling cross-coupling reactions with outer-sphere C–C coupling

“…14,15 For uoroalkenes, C-C couplings have been less studied and examples include group 10 catalysts and the use of gem-diuoroalkenes. [16][17][18][19][20][21][22][23][24][25][26][27][28] The couplings proceed by an initial C-F bond oxidative additionin some cases using lithium salts to promote the activation stepor insertion of a uorinated olen into a metal-carbon bond followed by b-uorine elimination. Cao and Wu developed a Suzuki-Miyaura cross coupling arylation of gem-diuoroalkenes using a nickel catalyst, 21 whereas Tsui and Liu applied a palladium catalyst.…”