Fluorinations boron trifluoride etherate

In the course of synthetic efforts aimed at obtaining 6j5-fluoro steroids, Kirk and Petrow treated a 3)5-acetoxy-6-raethyl-5a,6a-epoxide with boron trifluoride etherate and unexpectedly obtained a fluorine-free acetoxy ketone." Later transformations established that the product was the A-homo-B-norsteroid (104). 

The reactions of some fluorinated ethers may result in the elimination of alkyl fluorides In the case of 2-methoxyperfluoro-2-butene, treatment with antimony pentafluoride gives perfluoro-3-buten-2-one and methylfluoride [107] By reacting 2-chloro-l,l,2-trifluorodiethyl ether with boron trifluoride etherate or with aluminum chloride, chlorofluoroacetyl fluoride can be obtained with the elimination of ethyl fluonde [108] (equations 76 and 77)... 

With boron trifluoride-etherate, methanethiol and acetic acid fluorine is incorporated in almost quantitative yields. For example, the bis-dimethylamino-derivative 164 can be converted to l-fluoro-l-dimethylamino-2.4.6-triphenyl-phoshorin 172. ... 

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. 

Ethyl aluminum dichloride mediates a formal [5 + 2] cycloaddition of complex (164) and (166) with enol silyl ethers to produce the highly strained seven-membered rings (165) and (167) respectively (Schemes 239 -240). Excellent stereoselectivity is observed in both cases. A related double alkylation affords complexed seven-membered rings via a formal [4 - - 3] cycloaddition. Incorporation of fluorine is observed using boron trifluoride etherate (Scheme 241). 

The earlier work in 1993, when Cambie et al. synthesized the C-9 fluorine analogue of anthraquinones, showed that treatment of the anthraquinonyl chloroallyl acetal with boron trifluoride etherate at room temperature gave the 9-chloro-9-fluoro derivative with a low yield (4%) [33,34]. 

In 1993, Cambie et al. published the synthesis of the 9-chloro-9-fluoro derivative [33]. Subsequently, they continued to study the introduction of fluorine at C-9 into an anthracyclinone and later, in 1996, finished the synthesis of 9-fluoro-9-methylanthracyclinone 44 (Fig. 5). The 9-fluoro derivatives were achieved by treating ortho-methallyl-substituted anthraquinonyl homochiral dioxanes with boron trifluoride etherate. In this case, the yields of the fluoro derivatives were better than in the earlier work [36]. 

Fluorination of 5,7-dimethylpyrazolo[l,5-a]pyrimidine (275) in the 3-position has been achieved in low yield by treatment with tiifluoroacetic anhydride and boron trifluoride etherate in refluxing methylene dichloride evidence su ests that the expected 3-trifluoroacetyI derivative is an intermediate. 3-Fluoropyrroles have... 

Fluorination of m-carborane (2) with SbFj afforded 9-fluoro-m-carborane (36) and 9,10-difluoro-m-carborane (37) (Scheme 6.6) (Lebedev et al., 1990). The reaction of 38, which was synthesized according to the procedure discussed above for compound 14, with a boron trifluoride etherate complex afforded 2-fluoro-m-carborane (39, 65% yield) (Roscoe et al., 1970). Compound 2 was also reacted with BuLi and subsequently perchloryl fluoride in ether at -15°C to yield 1,7-difluoro-m-carborane (40), which was converted to dodecafluoro-m-carborane (41, 30% yield) by treatment with an excess of molecular fluorine in an HF suspension (Kongpricha and Schroeder, 1969). 

Diazotization in the presence of boron trifluoride enables diazonium tetrafluoroborates to be isolated from the reaction mixture and purified. Subsequent controlled decomposition produces the required fluoroaromatic. Although explosion hazards and the toxicity of the isolated salts are significant concerns with this process, known as the Balz-Schiemann process, 4,4 -di-fluorobenzophenone (BDF. 6) has been prepared by this route as a monomer for the production of the engineering plastic poly(ether ether ketone) , or PEEK , by condensation with 1,4-dihydroxybenzene in the presence of potassium carbonate. BDF 6 is superior to its chlorine analog because in aromatic systems the nucleophilic displacement of fluorine is more facile than that of chlorine, leading to a shorter polymerization time and a better quality product containing less degradation impurities. 

Introduction of Fluorine with Boron Trifluoride and Boron Trifluoride-Diethyl Ether Complex... 

Boron trifluoride-diethyl ether complex (2) is a colorless stable liquid which can be distilled at atmospheric pressure without decomposition. On exposure to wet air it fumes and it is sensitive to moisture with a loss of fluorinating activity. 

There are some reactions in which boron trifluoride and boron trifluoride-diethyl ether complex are used as fluorinating agents, but they are not so frequently used and widespread. The best-known reaction is the decomposition of fluoroformates. In this type of reaction boron trifluoride or pyridine are essentially required as catalysts for the decomposition process. The formation of fluoroformates is established4 5 and the decomposition proceeds cither by heating in pyridine at higher temperature6 or by addition of boron trifluoride-diethyl ether complex at 0-50°C.7... 

Furthermore, boron trifluoride is used as a catalyst to prepare fluorinated ethers from alcohols and carbon tetrachloride in hydrogen fluoride.19... 

Aromatic nitro compounds can be converted to the corresponding 4-fluoroanilines if the 4-position carries a hydrogen atom. Thus, nitrobenzene can be converted to 4-fluoroaniline with 100% conversion and 95% selectivity by heating with hydrogen under pressure [platinum(IV) oxide catalyst] in the presence of boron trifluoride-diethyl ether complex at 42°C for 12.5 hours. 3-Chloro-l-nitrobenzene can be similarly hydrogenated-fluorinated to 3-chloro-4-fluoroaniline.25,26... 

Fluoromalonates can be obtained in moderate yields by fluorination of the corresponding carbanions with xenon difluoride, dimethyl sulfide and boron trifluoride-diethyl ether complex.29... 

Investigation of the reaction of xenon difluoride and difluoroiodobenzene with aliphatic 1,3-dienes in the presence of boron trifluoride-diethyl ether complex has shown that under mild conditions this reaction proceeds with kinetic control, to form mainly the products of 1,2-addition of fluorine atoms. The ratio of product is reported in Table 5. 

Xenon difluoride reacts with alcohols to form unstable alkoxyxenon fluoride intermediates. Alkoxyxenon fluorides react as positive oxygen electrophiles when boron trifluoride-diethyl ether complex is used as a catalyst. However, these alkoxyxenon fluorides react as apparent fluorine electrophiles with proton catalysts (hydrogen fluoride generated in situ).49... 

Boron trifluoride-diethyl ether complex is used as catalyst in addition reactions of hydrogen fluoride to double bonds. If the alkene is halogenated on the C = C bond, fluorine adds to the carbon that bears the halogen.51... 

Grown Ethers. Ethylene oxide forms cyclic oligomers (crown ethers) in the presence of fluorinated Lewis acids such as boron trifluoride, phosphorus pentafluoride, or antimony pentafluoride. Hydrogen fluoride is the preferred catalyst (47). The presence of BF 4, PF y, or SbF 6 salts of alkali, alkaline earth, or transition metals directs the oligomerization to the cyclic tetramer, 1,4,7,10-tetraoxacyclododecane [294-93-9] (12-crown-4), pentamer, 1,4,7,10,13-pentaoxacyclopentadecane [33100-27-6] (15-crown-6), andhexamer, 1,4,7,10,13,16-hexaoxacyclooctadecane [17455-13-9]... 

The ether linkage of ordinary open-chain ethers is stable towards most fluorinating agents only few examples of the fluorination of dialkyl ethers are known. l-Fluorobicyclo[2.2.2]octane (2 a) and l-fluoro-4-methylbicyclo[2.2.2]oclane (2 b) can be obtained by treatment of the corresponding methyl ethers 1 with acetyl fluoride in the presence of boron trifluoride-phosphoric acid complex in good yield. ... 

Some examples of fluorination of substrates bearing group IV-A elements (Ge, Pb) have been reported.The best results are obtained in the reaction of aryllead(IV) triacetates 20 with boron trifluoride-diethyl ether complex. The yields of fluoroaromatics 16 are 50-80%. Triarylboroximes and aryltrimethylsilanes are precursors of the corresponding aryllead(IV) triacetates 20. ... 

Further examples of fluorinating ring-opening reactions of epoxides with the boron trifluoride-diethyl ether complex are given by the formation of 6.43 7,52 8,35 9.54 and 10.56... 

Table 17 indicates some limitations of the amine hydrofluorides in the reaction with glycidic esters. In the least-substituted case (entry 1) the yield is low. On the other hand, the fully substituted glycidic esters (entries 8 and 9) do not react at all with the amine hydrofluoride, probably due to steric hindrance. This type of epoxide gives better results with other fluorination reagents, e.g. they can be opened to the fluorohydrins in good yield with hydrogen fluoride in the presence of the boron trifluoride-diethyl ether complex (sec Section 1.1.4.3.2.1.2.).37... 

By reaction of a 1,1-difluoroethene with tributylphosphane in the presence of boron trifluoride-diethyl ether complex, the vinylphosphonium salt is obtained. On subsequent hydrolysis the selectivity of formation of the Z- and F-isomer is 100%, but it diminishes after the introduction into the alkene. together with the perfluoroalkyl group, of substituents such as phenyl and 4-methoxyphcnyl. In accordance with this methodology, a method of substitution of fluorine by hydrogen at the fluoroolefinic double bond has been developed.194,206 The first stage of this reaction includes the formation of a fluoro-/5-phosphane from the fluoroalkene and tributylphosphane. The decomposition of this /l5-phosphane in the aqueous solvent leads to a fluoroalkene, e.g. formation of l.206... 

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