Palladium-Catalyzed Anti-Markovnikov Hydroalkylation of Homoallylic Alcohols Bearing β-Fluorines

Abstract

A palladium-catalyzed anti-Markovnikov hydroalkylation of β,β-difluorinated homoallylic alcohols with alkylzinc reagents has been developed. This method affords a wide range of synthetically useful gem-difluorinated compounds with good functional group compatibility.

3,3,3-Bromodifluoro-1-propene: The Mild Introduction of CF2

“…11 (F) Zhang and co-workers directly coupled 3,3,3-bromodifluoro-1-propene to arylboronic acids with high regioselectivity (α-substitution) and chemoselectivity (aldehydes were unreacted under the reaction conditions). 12 (G) Ichikawa and co-workers found conditions for a selective γ-attack (S N 2′) of 3,3,3-bromodifluoro-1-propene by 1,2-bromoheteroarenes to give 3,3-difluoroallylic compounds which could undergo an intramolecular radical cyclisation to gain access to 3-difluoromethylated dihydrobenzoheteroles.…”

“…(E) Lin and Qing showed that the difluorohomoallylic alcohols and amines (prepared from the reactions shown above) could undergo an anti-Markovnikov hydroalkylation in the presence of an organozincate under palladium catalysis with an oxidant (benzoquinone under an air atmosphere). 11 (F) Zhang and co-workers directly coupled 3,3,3-bromodifluoro-1propene to arylboronic acids with high regioselectivity (α-substitution) and chemoselectivity (aldehydes were unreacted under the reaction conditions). 12 (G) Ichikawa and co-workers found conditions for a selective γ-attack (S N 2′) of 3,3,3-bromodifluoro-1-propene by 1,2-bromoheteroarenes to give 3,3-difluoroallylic compounds which could undergo an intramolecular radical cyclisation to gain access to 3-difluoromethylated dihydrobenzoheteroles.…”

Vinylation of Iododifluoromethylated Alcohols via a Light-Promoted Intramolecular Atom-Transfer Reaction

“…19 F NMR (282 MHz, CDCl 3 ): δ = -108.3 (dt, J = 246.6, 10.5 Hz, 1 F), -110.4 (dt, J = 246.6, 10.5 Hz, 1 F). (2,2-Difluoro-1-hydroxybut-3-en-1-yl)benzoate (3b) 27 Yield: 220 mg (91%); white crystals; mp 53-54 °C.…”

“…2,2-Difluoro-1-(furan-2-yl)but-3-en-1-ol (3n) 30 Yield: 155 mg (89%); yellow oil. 2,2-Difluoro-1-(thien-2-yl)but-3-en-1-ol (3o) 27 Yield: 150 mg (79%); yellow oil. R f = 0.33 (hexanes/EtOAc, 5:1).…”