Fluoro-Pummerer reaction

In most oases, the fluoro Pummerer reaction can be carried out with 1.33 to 2.0 equiv of DAST and a "catalytic" amount of antimony trichloride in either refluxing methylene chloride or chloroform at room temperature or 50°C. In the synthesis of fluoromethyl phenyl sulfide, however, the induction period makes room temperature conditions the preferred method for large scale synthesis. 

Electron-withdrawing groups decrease the rate of the fluoro Pummerer reaction, which, in certain cases,7 allows a DAST-mediated deoxygenation to compete with the introduction of fluorine alpha to sulfur. The reaction is compatible with a number of functional groups and can readily be carried out with nucleosides. Robins and coworkers4 reported the synthesis of a 5 -fluoro-5 -S-phenyladenosine analog using antimony trichloride as catalyst at room temperature. It should be noted that a-fluoro sulfoxides provide a convenient entry to terminal fluoroalkenes.3 8 9 10... 

DFIT-induced fluoro-Pummerer reactions of N-substituted-2-(phenylsul-fanyl)acetamides have also been reported (Scheme 37) [107]. With some amides, cyclization of the Pummerer intermediate was competitive with fluorination, and in other cases, fluorination was preempted by sulfoxide formation. 

Treatment of methyl phenyl sulfoxide with diethylaminosulfur trifluoride (DAST), in the presence of antimony trichloride provides 159 in quantitative yield (66). The reaction proceeds in good yield with dialkyl sulfoxides and alkyl aryl sulfoxides (163). Reoxidation of the a-fluorosulfide (165) to the corresponding sulfoxide (161), followed by pyrolysis, provides a direct synthesis of fluoroolefins (65). The reaction is believed to proceed by a Pummerer-type mechanism (l.e., a fluoro-Pummerer reaction, Scheme 48). Similarly, Umemoto (67) reported that N-fluorocollidine (167) converted sulfides to ot-fluorosulfides (170) presumably via an S-fluorosulfonium cation species 168 (Scheme 49). The synthetically challenging fluorovinyl ether nucleosides (175) and (176) were prepared using the fluoro-Pummerer reaction (Scheme 50) (60) the (E)-isomer (175) could be isomerized to 176 under photolytic conditions. Finch and co-workers (69) converted 160 to the sulfoximine 178 and demonstrated the utility of this compound as a mild fluoromethylene synthon (Scheme 51). Base-catalyzed condensation 178 with a carbonyl compound gave 179 which afforded... 

Organic fluorine compounds and methods for their preparation are the central topic of the next four procedures. Much of the synthetic versatility of methyl phenyl sulfone is embodied in FLUOROMETHYL PHENYL SULFONE and the fluoro Pummerer reaction of methyl phenyl sulfoxide with DAST is a key step in its preparation. The utility of this fluoromethyl sulfone in the preparation of fluoroalkenes Is demonstrated in a companion procedure for Z-[2-(FLUOROMETHYLENE) CYCLOHEXYL]BENZENE, a procedure with several prominent stereoselective features. Geminal difluoroalkenes are featured in the following procedure. (3,3 DIFLUOROALLYL)TRIMETHYLSILANE is prepared by a method in which the radical addition of dibromodifluoromethane to alkenes and the selective reduction of a-bromoalkylsilanes are key steps. A procedure for nucleophilic introduction of the trifluoromethyl group completes this set. The key reagent, (TRIFLUOROMETHYL)-TRIMETHYLSILANE is obtained by reductive coupling of TMS chloride and bromotrifluoromethane. Liberation of a CF3- equivalent with fluoride ion in the presence of cyclohexanone affords 1-TRIFLUOROMETHYL-1-CYCLOHEXANOL. 

Scheme 20.39 Mechanism of fluoro-Pummerer reaction with PAST and Znin-Scheme 20.40 Seleno-Pummerer reaction in the synthesis of nucleoside analogues. Scheme 20.41 Seleno-Pummerer in radical processes.

The literature on Pummerer chemistry is quite extensive, and multiple variants are described. However, looking deeply into these alternatives, it becomes apparent that most of them are based on the same principle, and the only variation is the nucleophile source. One example of this is the so-called fluoro-Pummerer reaction, which is in fact a fluoride addition to the normal Pummerer intermediate. The distinguishing feature is the generation of the thionium intermediate, using (diethylamino)sulfur trifluoride (DAST) in combination with metals (Scheme 20.391. DAST is known as a source of nucleophilic fluoride and has been widely used for this purpose. A review on the fluoro-Pummerer reaction was published by Haufe and coworkers in 2012. ... 

Scheme 20.39 Mechanism of fluoro-Pummerer reaction with DAST and ZnLr...

The Lewis acid-base reaction of SbCls with DAST, (diethylamino)sulfur trifluoride, can be used to catalyze the conversion of sulfoxides to a-fluorothioethers (Eq. 2) [7]. Zinc iodide was originally reported to be the catalyst for this fluoro-Pummerer transformation [8a], but SbCL is markedly superior [7,8b],... 

Reaction of thioethers with one equivalent of NF-reagent results in the formation of a-fluorothioethers via a fluoro-Pummerer rearrangement [199] (Scheme 2.90). With appropriate excesses a-fluorosulfoxides and sulfones are obtained [200]. The thiophenyl group can also be used as a subsequently removable directing function for site-selective fluorination of natural products [201]. 

The difluoroiodotoluene is an elfective reagent for the fluorination of a-phenelsul-fanyl lactones 95. The reaction involves fluoro-Pummerer rearrangment. A sequence involving conversion of a-fluorosulfide 95 into sulfoxide and elimination step was used for the synthesis of 3-fluoro-2(5H) furanones 96. ... 

A review of the scope and limitations of fluoro-Pummerer rearrangements, oxidative desulfiirization-fluorination, and oxidative desulfurization-di- and tri-fluorination reactions for the synthesis of fluorinated compounds has been reported. ... 

Sulfides are selectively fluorinated a to the sulfur atom via a reaction similar to the Pummerer rearrangement (Table 2). The fluorination wa.s originally achieved by the direct fluorination of sulfides with xenon difluoride.This reaction is proposed to occur by initial oxidative fluorination of the sulfide to give an unstable sulfur(IV) difluoride of type 1, followed by loss of hydrogen fluoride to give intermediate 2, followed by fluorine transfer to give the a-fluoro sulfide. This fluorination has also been achieved with diethylaminosulfur trifluoride (DAST) in the absence or presence of catalytic amounts of antimony(III) chloride (see Vol. ElOa, pp 421-423). ... 

Early studies in electrofluorination were conducted by fluorination of chiral benzylic esters at a platinum anode in EtaN x 3HF/CH3CN moderate diastereomeric excesses up to 60% were recorded (Scheme 44.29). The diastereo-selective anodic fluorination of A -protected thiazolidines derived from L-cysteine or sulfides gave the corresponding fluoro derivatives in a Pummerer-type reaction mechanism in moderate yields and high to very high diastereoselectiv-ities, up to 99% (Scheme 44.30). ... 

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