Deoxyfluorination of alcohols with 3,3-difluoro-1,2-diarylcyclopropenes

Abstract

Aromatic cation activation is a useful strategy to promote deoxyfunctionalization; however, the deoxyfluorination of alcohols with cyclopropenium cation remains an unsolved problem due to the weak nucleophilicity of fluoride ion. Here we report the use of 3,3-difluoro-1,2-diarylcyclopropenes (CpFluors) as easily accessible and reactivity-tunable deoxyfluorination reagents. The electronic nature of CpFluors is critical for fluorination of monoalcohols via alkoxycyclopropenium cations, and CpFluors with electron-rich aryl substituents facilitate the transformation with high efficiency; however, selective monofluorination of 1,2- and 1,3-diols, which proceeds via cyclopropenone acetals, is less dependent on the electronic nature of CpFluors. Moreover, CpFluors are more sensitive to the electronic nature of alcohols than many other deoxyfluorination reagents, thus fluorination of longer diols can be achieved selectively at the relatively electron-rich position. This research not only unveils the first example of deoxyfluorination reagents that contain an all-carbon scaffold, but also sheds light on the divergent reactivity of cyclopropenium cation in deoxyfunctionalization of alcohols.

Recent Developments in the Deoxyfluorination of Alcohols and Phenols: New Reagents, Mechanistic Insights, and Applications

“…The unique reactivity of CpFluor 42 is further illustrated by the outcome of its exposure to 1,2-and 1,3-diols 46 (Scheme 12). 22 Strikingly, in this situation monofluorinated products 47 are obtained in good to excellent yields. In addition, functionalities, such as alkyl halides and alkenes, are tolerated.…”

“…42 (Scheme 10), as a new class of deoxyfluorinating reagents. 22 It is notable that 42 bears an all-carbon skeleton, in contrast with most previous deoxyfluorinating reagents which tend to be based on heteroatoms (e.g., sulfur fluorides and their derivatives [SF reagents], or fluorinated alkylamines and their derivatives [NCF reagents]).…”

“…CpFluor 42b is an efficient deoxyfluorinating reagent, including with primary, secondary, and tertiary alcohols as substrates (Scheme 11). 22 Secondary alcohols react with inversion. Sensitive functional groups, such as aldehydes and ketones, are well tolerated (Scheme 11).…”

Fluolead (Ar-SF3) Deoxofluorination

“…Deoxofluorinating reagents are divided into next categories: a-fluorinated alkylamines (NCF reagents) and CpFluors [13,20,22,35,37] ( Fig. 1a) and sulfur fluorides and their derivatives (SF reagents) [3,17,21,26,38,41] (Fig.…”

Ar-SF 4 Cl Deoxofluorination

“…Among them, deoxo-and dethioxo fluorination methods involving the direct replacement of oxygen and/or sulfur moieties in substrates with fluorine are one of the most effective approaches for the selective synthesis of organofluorine compounds. Various reagents such as SF 4 [14], DAST (diethylaminosulfur trifluoride) [26], Deoxo-Fluor [bis(2-methoxyethyl)aminosulfur trifluoride] [3], DFI (2,2-difluoro-1,3-dimethylimid azolidine) [15], DFMBA (N,N-diethyl-a,a-difluorom-methylbenzylamine) [22], TFFH (fluoro-N,N,N 0 , N 0 -tetramethylformamidinium hexafluorophosphate) [9], PhenoFluor [1,3-bis(2,6-diisopropylphenyl)-2,2-difluoro-2,3-dihydro-1H-imidazole] [38], Cp Fluors (3,3-difluoro-1,2-diarylcyclopropene) [27], XtalFluor-E [(diethylamino)difluorosulfonium tet rafluoroborate] and XtalFluor-M (difluoro-4morpholinylsulfonium tetrafluoroborate) [3,25], Fluolead (4-tert-butyl-2,6-dimethylphenylsulfur t rifluoride) [42], and PyFluor (2-pyridinesulfonyl f luoride) [31] have been developed for this purpose. The title compounds, arylsulfur chlorotetrafluorides (ArSF 4 Cl), fluorinate many kinds of oxy-and su lfur-containing substrates such as alcohols, aldeh ydes, ketones, diketones, carboxylic acids, and su lfur compounds to corresponding fluoro-compou nds in the presence of reducing reagents.…”