Fluorination of boronic acids

Furuya T, Ritter T (2009) Fluorination of boronic acids mediated by silver (I) triflate. Org Lett ll(13) 2860-2863... 

Scheme 15.65 Ritter ligand for the fluorination of boronic acids.

The same authors have reported a new fluorination of boronic acids mediated by silver(i) triflate. ° The process and a range of examples are shown in Scheme 15.68. 

Wide spectrum of fluorinated aromatic compounds has been synthesized by electrophilic fluorination of arylboronic acids. So 3-fluoropyridine (63) has been obtained from 3-pyridine boronic acids 86 and F-TEDA-BF4 in 72 % yield [76] (Scheme 32). 

Compounds containing fluorine and chlorine are also donors to BF3. Aqueous fluoroboric acid and the tetrafluoroborates of metals, nonmetals, and organic radicals represent a large class of compounds in which the fluoride ion is coordinating with trifluoroborane. Representative examples of these compounds are given in Table 5. Coordination compounds of boron trifluoride with the chlorides of sodium, aluminum, iron, copper, 2inc, tin, and lead have been indicated (53) they are probably chlorotrifluoroborates. 

Manufacture. Boron trifluoride is prepared by the reaction of a boron-containing material and a fluorine-containing substance in the presence of an acid. The traditional method used borax, fluorspar, and sulfuric acid. 

The designation of hard acids is not restricted to metal cations. For example, in BF3 the small boron atom in its +3 oxidation state is bonded to three highly electronegative fluorine atoms. All the B—F bonds are polarized away from a boron center that is already electron-deficient. Boron trifiuoride is a hard Lewis acid. 

Boron being more electropositive than carbon, the fluorines of BF3 (-126 ppm) are more highly shielded than those of CF4 (-65 ppm). When this strong Lewis acid interacts with a Lewis base, as in BF3 OEt2... 

There are only a few examples of displacement of a fluorine atom in a cross-coupling reaction. With tricarbonylchromium complexes of fluoroarenes as substrates, cross-coupling with both boronic acids and vinylstannanes has been realized. Interestingly, only PMe3 is effective as ligand in this reaction (89).2" See Section 9.6.3.4.10 for an example of the involvement of unactivated fluoroarenes in cross-coupling reactions. 

The thiophene derivatives are relatively stable in the pure state. The fluorine atoms of the trifluoromethylmercapto group can be quantitatively substituted with chlorine by boron trichloride with HjOg, oxidation to the sulfone takes place. Further substitution is achieved in both cases in the presence of perfluorosulfonic acids ... 

The hydrogen fluoride catalyzed fluorination of norbornene by xenon difluoride at room temperature leads to a mixture of at least seven components,39 but under milder conditions (— 78 to 26 C, 22 hours) the reaction affords a mixture of two main products 2-e,xo-5-cxo-difluoro-norbornane and 2-c-wfo-5- Yo-difluoronorbornane, ratio 2 1, in a total yield of 51-76%. If the same reaction is carried out in a limited temperature range between — 46 and — 39 C the yield of these products decreases, their ratio becomes equal, and the main product is 2-exo-l-ff //-difluoronorbornane (42 %).40 The structure dependence of the fluorination products of norbornene with xenon difluoride was studied. Solvent, temperature, reaction duration, catalyst (hydrogen fluoride, boron trifluoride, trifluoroacetic acid, pentafluorobenzenethiol) and the routes of product isomerization were analyzed.41-42... 

A novel method for the convenient synthesis of alkenyl fluorides 15, as well as diflu-oromethyl-substituted alcohols 16 and amides 17, via electrophilic fluorination with one equivalent of F-Teda BF4 (6) of alkenyl boronic acids and trifluoroborates, has been reported.87 The alkenyl fluorides 15 are obtained as Z/E mixtures when the reaction is carried out with one equivalent of F-Teda BF4 in acetonitrile at room temperature. When the reaction is performed with two equivalents of F-Teda BF4 in water or a nitrile solvent the difluoromethyl-substituted alcohols 16 or amides 17, respectively, are obtained. 

Introduction of Fluorine with Boron Trifluoride and Tetra-fluoroboric Acid Complexes and Salts of Tetrafluoroboric Acid... 

The addition of boron trifluoride as a catalyst has been found to be essential in the fluorination of carboxylic groups of poly(acrylic acid) and poly(methacrylic acid) with sulfur tetrafluoride.12 Boron trifluoride as a Lewis acid is necessary in catalytic amounts to polarize the C = 0 bond before fluorination with molybdenum(VI) hexafluoride takes place.1314... 

Substitution of hydrogen by fluorine in compounds with acidic a-hydrogens can be achieved with xenon difluoride and some catalysts. Thus, room-temperature fluorination of 1,3-diketones, e g. 20, with xenon difluoride in the presence of the insoluble cross-linked polysty-rene-4-vinylpyridine, either complexed with boron trifluoridc or Nafion-H, as catalyst, gives mono and difluoro products.27-28... 

As noted above, the hardness or softness of an acidic or basic site is not an inherent property of the particular atom at that site, but can be influenced by the substituent atoms The addition of soft, polarizable substituents can soften an otherwise hard center and the presence of electron-withdrawing substituents can reduce the softness of a site. The acidic boron atom is borderline between hard and soft. Addition of three hard, electronegative fluorine atoms hardens the boron and makes it a hard Lewis acid. Conversely, addition of three soft, electropositive hydrogens54 softens the boron and makes it a soft Lewis acid. Examples of the difference in hardness of these two boron acids are... 

Enamels - [BARIUMCOMPOUNDS] (Vol3) - [ALUMINUMCOMPOUNDS - ALUMINIUMOXIDE(ALUMINA) - CALCINED,TABULAR, AND ALUMINATE CEMENTS] (Vol2) - [TIN COMPOUNDS] (Vol 24) -aluminum fluoride in [FLUORINE COMPOUNDS,INORGANIC - ALUMINUM](Vol 11) -antimony compds in [ANTIMONY COMPOUNDS] (Vol 3) -borate in [BORON COMPOUNDS - BORON OXIDES, BORIC ACID AND BORATES] (Vol 4) -boric oxide in prepn of [BORON COMPOUNDS - BORON OXIDES, BORIC ACID AND BORATES] (Vo 14) -lithium for [LITHIUM AND LITHIUM COMPOUNDS] (Vol 15)... 

The benzene derivatives containing the fluorinated sulfone have been prepared either by nucleophilic substitution of the 4-fluorophenyl derivative (e.g. 1) or by starting with the appropriately substituted sodium thiophenoxide and reacting with perfluoroalkyl iodide follow by oxidation with either MCPBA or chromium oxide (12. li.) The biphenyl derivatives have been prepared by palladium catalyzed cross coupling chemistry of the 4-bromophenyl derivative (e.g. 2) with substituted phenyl boronic acid (yields 37-84%) (JLH, .). Compound 16 has been prepared by palladium catalyzed cross coupling of (4-bromophenyl)perfluorohexyl sulfone with vinyl anisole in 37 % yield (JJL). The vinyl sulfones, 7 and 9, have been prepared by condensation of CH3S02Rf (JJL) with the appropriate aldehyde (yields 70,and 73%) following a literature procedure (1 ). Yields were not optimized. 

An efficient aqueous phase Suzuki-Miyaura reaction of activated aryl chlorides with aryl boronic acids has been reported. The method uses a new D-glucosamine-based dicyclohexylarylphosphine ligand for the palladium catalyst and works well with nitro-and cyano-activated chlorides.32 The aryl fluoride bond has been considered inert to palladium-catalysed substitution reactions. However, a computational study, backed up by experiment, shows that the presence of a carboxylate group ortho to fluorine will allow reaction both with phenylboronic acids in a Suzuki-type reaction and with organotin reagents in a Stille-type reaction the presence of the adjacent oxyanion stabilizes the transition state.33... 

Earlier studies have already demonstrated that in acid-catalyzed fluorination of norbornene, 2,3-difluoro products were also formed via radical intermediates, their amounts depending significantly on the presence of oxygen as scavenger69. Catalyst and temperature also had a significant effect on the reaction pathways, boron trifluoride ether-ate favoring the formation of l-endo-S-exo-axid. 2-exo-5-ex0-difluoro norbornane, while pentafluorothiophenol favored the formation of fluoronortricyclane70-72. 

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