Regioselective Synthesis of α,α-Difluorocyclopentanone Derivatives: Domino Nickel-Catalyzed Difluorocyclopropanation/Ring-Expansion Sequence of Silyl Dienol Ethers

Abstract

Silyl dienol ethers prepared from α,β-unsaturated ketones underwent nickel-catalyzed difluorocyclopropanation of the electron-rich alkene moiety with trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate. The subsequent vinylcyclopropane-cyclopentene rearrangement afforded silyl 5,5-difluorocyclopent-1-en-1-yl ethers in good yields. The obtained five-membered silyl enol ethers were demonstrated to be versatile intermediates for the synthesis of di- and monofluorinated cyclopentanones and cyclopentenones. A nickel difluorocarbene complex is proposed as a key intermediate in the difluorocyclopropanation.

Chelating Bis(N‐Heterocyclic Carbene) Palladium‐Catalyzed Reactions

“…Additionally, compound 38 was also found to be an active catalyst in the Suzuki–Miyaura and Sonogashira reactions (with cocatalyst CuI) . Then, Ichikawa and co‐workers described the activity of complexes 37 and 38 in the difluorocyclopropanation of silyl enol ethers . Later, three pincer‐type palladium‐methyl complexes, such as 40 , were prepared by Cavell and co‐workers through transmetalation with [PdClMe(cod)] (cod=1,5‐cyclooctadienyl) as a precursor .…”

“…[25] Then, Ichikawaa nd co-workers described the activity of complexes 37 and 38 in the difluorocyclopropanation of silyl enol ethers. [26] Later,t hree pincer-type palladium-methyl complexes, such as 40,w ere prepared by Cavell and co-workers through transmetalation with [PdClMe(cod)] (cod = 1,5-cyclooctadienyl) as ap recursor. [27] Complex 40 (1.01 10 À3 mol %), with bulky Mes side arms, displayed the highest activity (TON % 6 10 4 )i n the coupling reactionb etween n-butyl acrylate and 4-bromoacetophenone.…”

Metal-free synthesis of α,α-difluorocyclopentanone derivatives via regioselective difluorocyclopropanation/VCP rearrangement of silyl dienol ethers

“…Trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate (TFDA) was prepared according to the literature. 13 All of silyl dienol ethers (starting materials) 1a-j were prepared according to the literature 7,17 and the spectral data were in good agreement with those in the literature. 7,17 1,8-Bis(dimethylamino)naphthalene (proton sponge) and 1,1,1,3,3,3-hexafluoro-2,2-di(p-tolyl)propane (internal standard for 19 F NMR) was purchased from Tokyo Chemical Industry Co., Ltd. Proton sponge was recrystalized from methanol/water.…”

“…7 The reaction involves sequential (i) nickel-catalyzed chemoselective difluorocyclopropanation of silyl dienol ethers via a difluorocarbene complex and (ii) regioselective vinylcyclopropane/cyclopentene (VCP) rearrangement. [8][9][10] This method is efficient because the introduction of fluorine substituents and the construction of the carbon skeleton are performed simultaneously.…”

N‐Difluorocyclopropyl‐Substituted Pyrazoles: Synthesis and Reactivity

“…While a number of papers describe synthetic approaches to the compounds having a gem ‐difluorocyclopropyl group attached to the carbon atom, as well as their chemical transformations,, the corresponding N ‐substituted analogues are much less studied. Most of them referred to the parent gem ‐difluorocyclopropylamine ( 5 ) or its derivatives (Scheme );, it should be noted that similar aliphatic amines (e.g.…”