Alkyl fluorides synthesis fluorination

Summarizing, it can be stated that hydrogen fluoride/pyridine and hydrogen fluoride/amine mixtures are useful for the synthesis of simple secondary and tertiary alkyl fluorides, but probably arc not suitable for fluorination reactions in complex multifunctional structures due to the highly acidic properties of these reagents. 

Alkyl fluorides are valuable compounds for study as well as convenient precursors for the construction of complex organic architectures with a high degree of functionalization. A range of routes have been devised for the synthesis of these compounds, and a number of reviews on the synthesis of alkyl fluorides have appeared [1-6], One of the most direct routes to the preparation of an alkyl fluoride would be the deoxyfluorination of alcohols. Fundamentally, this would be analogous to a fluorine version of the Appel reaction, and while the Appel reaction is one of the most successful approaches to the synthesis of alkyl chlorides and bromides [7], it has been challenging to extend the chanistry to the preparation of aUcyl fluorides [6],... 

The Hiyama coupling offers a practical alternative when selectivity and/or availability of other reagents are problematic. Hiyama et al. coupled alkyltrifluorosilane 74 with 2-bromofuran 73 to give the corresponding cross-coupled product 75 in moderate yield in the presence of catalytic Pd(Ph3P)4 and 3 equivalents of TBAF [65]. In this case, more than one equivalent of fluoride ion was needed to form a pentacoordinated silicate. On the other hand, alkyltrifluorosilane 74 was prepared by hydrosilylation of the corresponding terminal olefin with trichlorosilane followed by fluorination with C11F2. This method provides a facile protocol for the synthesis of alkyl-substituted aromatic compounds. 

Both aromatic and aliphatic fluoroformates 7 can be readily prepared from phenols or alcohols and carbonyl difluoride and treated with sulfur tetrafluoride without isolation. Hydrogen fluoride evolved in the reaction of hydroxy compounds with carbonyl di fluoride serves as a catalyst for the consecutive reaction with sulfur tetrafluoride.15<)-162 This provides a general, convenient, direct synthesis of aryl and alkyl trifluoromethyl ethers 5 from phenols and alcohols. When the intermediate fluoroformate 7 is isolated prior to treatment with sulfur tetrafluoride, at least one mole equivalent of hydrogen fluoride is necessary to promote the fluorination reaction. 159 163 Representative examples of the conversion of hydroxy compounds 6 into trifluoromethyl ethers 5 via intermediate fluoroformates 7 are given (for other examples 7 -> 5, see Houben-Weyl, Vol. E4, pp 628. 629). 

Perfluorinated alkyl iodides are very important intermediates for the synthesis ofperfluoroalkyl-substituted compounds. They can be prepared by addition of fluorine and iodine to fluorinated alkenes. This addition can be carried out with various sources of IF" fluorine/iodine,225 226 hydrogen fluoride/iodine,190-297"308-313-31 5 potassium fluoride/iodine,l88-293 294-299 iodine pentafluoride/iodine,168 187-208 230 233 235-230 242-293-295 296-30 302-307 or iodine trifluoridc/ iodine.208-305... 

Perfluoroalkanesulfonyl fluorides and of related materials are manufactured by the electrochemical fluorination of the corresponding alkanesulfonyl fluorides or cyclic sulfonesP This electrochemical synthesis results in replacement of all C-H bonds in the feedstock. The perfluorinated alkanesulfonyl fluoride products are neutralized to make the anhydrous salt, then acidified and distilled to afford the anhydrous sulfonic acid. Alkyl chain degradation in the electrochemical cell becomes more pronounced at longer chain lengths. Addition of short-chain divalent sulfur compounds (e.g., thiols, sulfides) to the cell inhibits buildup of tarry materials and loss of efficiency. 

The full paper on the synthesis of 14 -fluoro-steroids by perchloryl fluoride fluorination of A -17-acetates has now appeared. It has been shown that 16a-bromoacetoxyprogesterone alkylates cysteine, histidine, methionine, lysine, and /5-mercaptoethanol under physiological conditions. 

Kuroboshi, M. Shinozaki, T. Ishihara, T. Ando, T. A convenient synthesis of fluorine-containing highly-substituted furans through new fluoride ion-catalyzed reaction of l-alkyl-F-l-alkenyl phosphates. Chem. Lett. 1987, 1621-1622. 

Fluorine may be introduced into the 5-position of 5-alkyl- and 5-aryl-barbituric acids by use of perchloryl fluoride, FCIO3, in mcthanol. The synthesis of l-(tetra-... 

Perfluoroalkanesulfonamides have been claimed as intermediates for the synthesis of fluorinated surfactants. Their synthesis by reaction of the corresponding perfluoroalkanesulfonyl fluoride (or chloride) with liquid ammonia is prototypical for the synthesis of alkylated perfluoroalkane-sulfonamide surfactants. This reaction initially forms a complex ammonium salt as shown in Scheme 18.2. The desired amide is obtained by dissolving the crude product in dioxane and... 

Trifluoromethylmalonic acid derivatives were used in the synthesis of 5-trifluoromethyl-substituted pyrimidines. In particular, acyl fluorides 827 were obtained by alkylation of trifluoromethyhnalonyl fluoride (826), in turn prepared from acyl fluoride 825 (Scheme 164) [509], Reaction of 827 with urea led to the formation of fluorinated barbitmates 828. 

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