Chain-extension reactions via insitu capture of the dibromofluoromethide ion with difluoromethylene fluoro-olefins

The insitu reaction of triphenylphosphine, tribromofluoromethane, and a difluoromethylene olefin successfully allows the capture of the intermediate dibromofluoromethide ion. With fluorinated propenes, the product is an allylic dibromofluoromethyl alkene; with longer chain fluoro-olefins the major product is a 1-bromo-1,3-fluorinated diene derivative. Pentafluoropyridine yields 4-dibromofluoromethyltetrafluoropyridine.


Introduction
Fluoro-olefins, especially difluoromethylene olefins, react with a wide variety of nucleophiles. 1,2n the absence of a proton source, the intermediate carbanion can eliminate fluoride ion to regenerate the double bond (Scheme 1).

Scheme 1
If the nucleophile is a carbanion, this process provides a chain extension.Possible side reactions include proton abstraction by the intermediate carbanion (

Scheme 3
product olefin with a second equivalent of the nucleophile (Scheme 4).Nevertheless, there are many examples which demonstrate that the substitution process is a viable route to chainextended fluoro-olefins.

Scheme 6
If the initial ylide/olefin reaction generated a new difluoromethylene olefin center, the initially formed phosphonium salt could react with a second equivalent of the ylide to produce a bis-phosphonium salt, which on hydrolysis gave a two carbon chain-extended diene product, as illustrated in Scheme 7. 7 Halofluoromethide ions constitute another class of fluorine-containing The bromodifluoromethide ion 3 was also formed by treatment of bromodifluoromethyltriphenylphosphonium bromide 4 with KF and again trapped with olefin 2 (Eq.3). 9 Thus, there is reasonable evidence that halofluoromethide ions can be trapped by appropriate fluoro-olefins to yield chain-extended olefins.

Results and Discussion
An initial attempt was made to carry out the chain-extension of olefin 2 with LiCFBr2, generated from n-BuLi and CFBr3 5 in THF/hexane at -110°C. 10 Subsequent addition of olefin 2 and analysis of the reaction mixture (after warming to RT) gave no evidence for any reaction of olefin 2. Apparently, LiCFBr2 decomposed faster than reaction with the olefin.
Tertiary phosphines react with fluorotrihalomethanes to form phosphonium salts. 11The mechanism of phosphonium salt formation is not an SN2 process, but involves halophilic attack on the halogen (other than fluorine) by the tertiary phosphines to form an ion-pair, followed by recombination of the ion-pair, as illustrated in Scheme 8.This mechanistic interpretation is supported by the observation that only the phosphonium salt is obtained when dry solvent is utilized (Path A); but the product is CFHX2 when water or ethanol are present (Path B).

Scheme 8
2][13] Since the dibromofluoromethide ion 6 could be generated readily (from 5) by the process described in Scheme 8, it was of interest to determine whether the carbanion 6 generated in this manner could be captured by a fluoro-olefin faster than recombination of the ion-pair to form the phosphonium salt.The dibromofluoromethide ion 6 differs from chlorodifluoromethide 1 and bromodifluoromethide 3 in two important ways.Carbanions 1 and 3 are unstable and rapidly lose halide ion to form difluorocarbene, Equation 4.
It has also been demonstrated that dibromofluoromethide carbanion 6 loses halide in a irreversible process. 16Secondly, it is known that halogens stabilize carbanions in the order I -~ Br -> Cl -> F -, but that dihalocarbenes are stabilized by halogens in the reverse order: F > Cl > Br > I. 17 Thus, it seemed reasonable that carbanion 6 should have a better opportunity to be captured by a fluoro-olefin than carbanions 1 or 3.
It is also been demonstrated that the initially formed phosphonium salt (from CFBr3 5) reacts with a second equivalent of tertiary phosphine to produce the bromofluoromethylene ylide and a dihalophosphorane, as illustrated in Equation 5. 11,13 Thus, an alternative mechanism might involve attack by the ylide on the fluoro-olefin, as shown in Scheme 9.However, when 2-phenylpentafluoropropene 2 was present during the addition of CFBr3 5 to a solution of Ph3P: 7, 92% of (Z)-CFBr2CF=C(Ph)CF3 was observed via 19 F NMR analysis of the reaction mixture.

Scheme 9
Apparently, carbanion 6 was trapped faster by olefin 2 before recombination of the ion-pair.Thus, this alternative mechanism either does not compete for fluoro-olefin or is only a minor pathway. 18he success of the trapping of carbanion 6 depended on the presence of a terminal difluoromethylene group in the olefin, and a carbanion-stabilizing group(s) on the -carbon of the fluoro-olefin.But it was also important that the fluoro-olefin not be so reactive that it would react directly with Ph3P 7. 19 For example, F2C=C(Ph)CF2Cl, F2C=CFCF2Cl.F2C=CFC(CF3)=C(CF3)H and perfluorocyclobutene 20 reacted directly with Ph3P and failed to give chain-extended product.
Similar results were obtained with F-1-pentene and F-1-nonene, (see Table 1, entries 7-9).Mechanistically, the bromodienes can be rationalized via further reaction of the initially formed addition-elimination product(s) 21 with either Ph 3 P 7 or CFBr 2 6, as illustrated in Scheme -10.The stereochemistry of the dienes was determined from 19 F-NMR coupling constants, and the (E)-and (Z)-3 JFF are readily distinguished by the magnitude of the vinyl coupling constants.

Conclusions
When triphenylphosphine and tribromofluoromethene are allowed to react in the presence of an appropriate difluoromethylene fluoro-olefin, the intermediate dibromofluoromethide ion is captured by the fluoro-olefin.With hexafluoropropene and 2-substituted trifluoropropenes, the addition-elimination product is formed.With longer chain 2-substituted difluoromethylene olefins, the 1-bromo-1,3-substituted dienes are the major product(s).Similar diene formation is observed with perfluoro-1-alkenes.The capture of the dibromofluoromethide ion results in a chain-extension process.With pentafluoropyridine, 4-dibromofluoromethyltetrafluoropyridine is formed in moderate yield.

Experimental Section
General.RT denotes room temperature. 1H-NMR spectra were recorded on a Jeol FX90Q spectrometer in CDCl3.Chemical shifts are in ppm relative to internal TMS. 19F-NMR spectra were recorded either on a Varian HA-100 (CW) or Jeol FX90Q (FT) spectrometer.Chemical shifts are given in ppm upfield from internal CFCl3, and were generally recorded in CDCl3, neat or triglyme (TG). 13C NMR spectra were recorded on a Bruker HX-90E or JEOL FX90Q spectrometer, with chemical shifts reported in ppm relative to TMS.Infrared spectra were recorded for liquid films between sodium chloride plates on a Beckman Accu Lab 8 instrument.Low resolution mass spectra were recorded on a Hitachi-Perkin Elmer RMU-6E mass spectrometer or a Hewlett-Packard 5985 GC/MS system at 70 eV.High resolution mass spectra were obtained from the Midwest Center for Mass Spectrometry at the University of Nebraska, Lincoln, NE.GLPC analyses were carried out on either a Hewlett-Packard 5840A or an F & M Materials.Triglyme (TG) and tetrahydrofuran (THF) were distilled from sodium benzophenone ketyl.Fluoroethylenes and hexafluoropropene were obtained from commercial sources and used as received.2-phenylpentafluoropropene and substituted 2-phenyl difluoromethylene olefins were prepared by the literature procedure. 25,26F-1-pentene, F-1-heptene and F-1-nonene were prepared by the literature procedure. 27Tribromofluoromethane was prepared by the literature procedure. 28Triphenylphosphine, pentafluoropyridine, potassium fluoride, and n-BuL/hexane were purchased from commercial sources.