A Novel and Highly Efficient Synthesis of gem-Difluorocyclopropanes

Abstract

[reaction: see text] A new and highly versatile source of difluorocarbene is reported. Trimethylsilyl fluorosulfonyldifluoroacetate (TFDA) undergoes decomposition in the presence of catalytic fluoride to form difluorocarbene under conditions that allow its addition to relatively electron deficient alkenes in high yield. For example, unprecedented CF2: addition to n-butyl acrylate proceeded in 73% yield.

Trimethylsilyl fluorosulfonyldifluoroacetate (TFDA): a new, highly efficient difluorocarbene reagent

“…On the basis of the ratios that were obtained, the following relative reactivities were obtained: 4.6. General procedure for preparation of n-butyl 2,2-difluorocyclopropanecarboxylate [14,15] A three-necked, round-bottomed flask was equipped with a magnetic stirrer, an addition funnel, and a water-cooled condenser bearing a nitrogen (N 2 ) inlet. The flask was charged with toluene, sodium fluoride (0.06 equivalent) and n-butyl acrylate.…”

“…Recently, we reported the discovery of a new difluorocarbene reagent, TFDA, that allows :CF 2 to be generated under conditions where it can add efficiently to even quite unreactive alkenes, such as acrylate esters [14,15].…”

“…TFDA, trimethylsilyl fluorosulfonyldifluoroacetate [16][17][18], can be conveniently prepared via the reaction of fluorosulfonyldifluoroacetic acid with trimethylsilylchloride [14,15]. The fluorosulfonyldifluoroacetic acid precursor remains expensive, but as shown below, deriving ultimately from the sultone formed by reaction of SO 3 with TFE [19], it can itself be prepared from the considerably less expensive fluorosulfonyldifluoroacetyl fluoride by treatment with water in a hydrocarbon solvent [19].…”

Chemistry of Difluorocarbene: Synthesis and Conversion of Difluoro(methylene)cyclopropanes

“…Recently, though, trimethylsilyl fluorosulfonyldifluoroacetate (FO 2 SCF 2 CO 2 SiMe 3 , TFDA), which can be easily prepared from considerably less expensive materials, has been reported to be a highly versatile source of difluorocarbene. [6] Dolbier and our group found that difluorocarbene generated from TFDA can add efficiently and effectively to a variety of alkynes and alkenes under mild conditions. [7] Difluoro(methylene)cyclopropane backbones might be directly accessible by difluorocarbene addition to allenic compounds or their equivalents, [8] and several attempts to explore this possibility have been made.…”

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

“…Recently, we have also developed an organocatalytic method for the generation of difluorocarbene by the decomposition of trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate (TFDA) [11][12][13] (Scheme 2). [14][15][16][17] The compound 1,8-bis(dimethylamino)naphthalene (proton sponge) was an efficient catalyst for the generation of difluorocarbene, with which silyl dienol ethers were chemoselectively transformed to the corresponding difluoro(vinyl)cyclopropanes, leading to the generation of α-fluorocyclopentenones via a fluorine-directed and -activated Nazarov cyclization (Scheme 3, Path A).…”