A remarkable room temperature preparation of the trifluorovinylzinc reagent from HFC-134a. A cost-effective, high yield synthesis of α,β,β-trifluorostyrenes

Article abstract of DOI:10.1016/S0040-4039(02)00397-0

The reaction of LDA (2.0 equiv.) with a THF solution of ZnCl₂ (1.0 equiv.) and CF₃CFH₂ (HFC-134a) (1.2 equiv.) at 15-20°C gives a 73% yield of [F₂C=CFZnCl]. Addition of R-C₆H₄I and Pd(PPh

Full text of DOI:10.1016/S0040-4039(02)00397-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2731–2733
A remarkable room temperature preparation of the
trifluorovinylzinc reagent from HFC-134a. A cost-effective,
high yield synthesis of a,b,b-trifluorostyrenes
R. Anilkumar and Donald J. Burton*
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
Received 1 February 2002; accepted 21 February 2002
Abstract—The reaction of LDA (2.0 equiv.) with a THF solution of ZnCl2 (1.0 equiv.) and CF3CFH2 (HFC-134a) (1.2 equiv.)
at 15–20°C gives a 73% yield of [F2CꢀCFZnCl]. Addition of R-C6H4I and Pd(PPh3)4 at rt to 65°C gives 61–86% yield of
R-C6H4CFꢀCF2. © 2002 Elsevier Science Ltd. All rights reserved.
Interest in a,b,b-trifluorostyrene (TFS) as a monomer
has received increased attention in recent years. In
particular, co-polymers have received interest as ion-
exchange membranes for fuel cell separators, dialysis
membranes, and packing materials for liquid chro-
matography columns.1 The challenge in the applica-
tions of TFS has been the preparation of TFS itself.
Numerous strategies have been employed to prepare
this monomer in an efficient and cost-effective manner.2
Acylation methodology3 and dehydrohalogenation of
fluorine-containing ethyl benzene derivatives4 gave low
overall yields (<20%) of TFS. Dixon reacted aryllithium
reagents with tetrafluoroethylene (TFE) to give TFS,
but the styrene product reacted rapidly with a second
equivalent of PhLi—thus reducing the overall yield of
TFS (Scheme 1).5 Even with excess TFE, the disubsti-
tuted product was favored.6
R-C6H4I in the presence of Pd(PPh3)4 gave improved
yields of TFS derivatives; however, the trifluorovinyl-
zinc intermediate was prepared at low temperature
(−120°C) via reaction of trifluorovinyllithium with zinc
halides.10 Recently, we developed a room temperature
preparation of trifluorovinylzinc derivatives via direct
insertion of Zn(0) into F2CꢀCFX (X=Br, I).11 Subse-
quent coupling of the trifluorovinylzinc reagent with
R-C6H4I in the presence of Pd(PPh3)4 provided excel-
lent isolated yields of substituted TFS derivatives via a
one-pot procedure,12 and this route has become the
method of choice by the chemical community.
Although this methodology provided the first room
temperature entry to TFS in high yield, it required the
use of F2CꢀCFX (X=Br,I); which, although commer-
cially available, are not necessarily cheap precursors—
particularly for commercial preparation of TFS. In
addition, the lack of large volume availability of
F2CꢀCFX also limited the commercial application of
this methodology.
Substituted TFS derivatives were also prepared by this
route.7 Organometallics, such as PhLnI, PhYbI and
PhNa, with TFE gave similar results.8 Pyrolytic routes
have been patented, but they generally provided only
low yields of TFS.9 Trifluorovinylzinc derivatives with
The only viable cheap, large volume, commercially
available precursor for the introduction of a tri-
fluorovinyl group is 1,1,1,2-tetrafluoroethane (HFC-
134a). Coe and co-workers recognized the potential of
HFC-134a as a trifluorovinyl synthon in 1999.13 They
generated trifluorovinyllithium from HFC-134a at
−78°C by a sequence of dehydrofluorination and metal-
lation reactions and carried out low temperature
functionalization reactions with various electrophiles
(Scheme 2).13,14 When zinc halides were utilized as the
Scheme 1.
Keywords: 1,1,1,2-tetrafluoroethane; HFC-134a; trifluorovinylzinc;
trifluorovinyllithium; trifluorostyrenes; Pd(0) coupling.
* Corresponding author. Fax: 319-35-1270; e-mail: donald-burton@
uiowa.edu
Scheme 2.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00397-0

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R. Anilkumar, D. J. Burton / Tetrahedron Letters 43 (2002) 2731–2733
cheap, commercially available HFC-134a via the in situ
capture of [F2CꢀCFLi] with zinc halide, when LDA is
utilized as the base. Subsequent Pd(0) coupling of the
zinc reagent with aryl iodides gives the resultant TFS
derivatives. Overall, this methodology provides the first
Scheme 3.
room temperature preparation of
a trifluorovinyl
organometallic reagent by in situ capture of tri-
fluorovinyllithium, and affords a new, cost-effective
ambient temperature route to TFS and its derivatives.
Work is in progress with other CF3CH2X (X=Cl, Br, I,
CF3) derivatives, as well as other metal halide trapping
agents, to elucidate the generality of this new, in situ
approach.
electrophile, F2CꢀCFZnX was formed and subse-
quently coupled with R-C6H4I in the presence of
Pd(0).13,15 This route offered a solution to the cost-
effectiveness problem, but the use of low temperature
(−78°C) precluded scale-up for any commercial applica-
tion. One needs to form [F2CꢀCFZnX] at temperatures
compatible with scale-up (0°C–rt). In addition, since
[F2CꢀCFLi] readily decomposes13 to difluoroacetylene
at temperature >−70°C, the formation of the zinc
reagent must be accomplished in situ at these higher
temperatures.
Acknowledgements
We thank Dr. Charles Stone for stimulating discussions
and insights into this problem, and we thank Ballard
Advanced Materials (BAM) for financial support of
this project.
We now wish to report that when a THF solution of
HFC-134a and anhydrous zinc chloride is treated with
LDA at 15–20°C, a 73% yield16 of the trifluorovinylzinc
reagent is formed (as detected by 19F NMR analysis of
the reaction mixture). Bases, such as t-BuLi, s-BuLi,
n-BuLi, LHMDS and t-BuO− were significantly less
effective under these reaction conditions. The diiso-
propylamine complexing agent, formed in situ in the
LDA reaction outlined below, is necessary to obtain
high yields of the zinc reagent (Scheme 3).
References
1. (a) Stone, C.; Daynard, T. S.; Hu, L.-Q.; Mah, C.; Steck,
A. E. J. New Mater. Electrochem. Syst. 2000, 3, 43–50;
(b) Stone, C.; Steck, A. E. PCT Int. Appl. WO
2001058576; (c) Momose, T.; Kitazumi, T.; Ishigaki, I.;
Okamoto, J. J. Appl. Polym. Sci. 1990, 39, 1221–1230; (d)
Wodzki, R.; Narebska, A.; Ceynowa, J. Angew. Makro-
mol. Chem. 1982, 106, 23–35; (e) Plummer, C. W.; Enos,
J.; LaConti, A. B.; Boyack, J. R. US Office Saline Water,
Res. Develop. Progr. Rep. 1969; (f) Kataev, A. D.;
Saburov, V. V.; Reznikova, O. A.; Kapustin, D. V.;
Zubov, V. P. J. Chromatogr. A 1994, 660, 131–136.
2. cf. Nikitina, T. S. Usp. Khim. 1990, 59, 995–1020 for a
review of a,b,b-trifluorostyrene and its polymers.
Addition of an aryl iodide and Pd(PPh3)4 to the solu-
tion of the complexed trifluorovinylzinc reagent and
warming (rt–65°C) provided the TFS derivative in 61–
86% isolated yields (based on aryl iodides). Table 1
summarizes the synthesis of several TFS derivatives
prepared by this methodology.
In conclusion, a remarkable room temperature prepara-
tion of [F2CꢀCFZnCl] has been achieved from the
Table 1. Preparation of a,b,b-Trifluorostyrenes from HFC-134a
Entry
R
Temp./time
Styrene
NMR yield (%)
Yield (%)a,b
1
2
3
4
5
6
7
8
H
p-F
65°C/3 h
65°C/4 h
rt/15 h
60°C/1 h
65°C/2 h
rt/12 h
C6H5CFꢀCF2
p-FC6H4CFꢀCF2
99
95
84
94
96
95
95
98
69
64
61
82
86
75c
67
74
m-NO2
p-MeO
o-(CH3)2CH
p-Br
m-CF3
o-F
m-NO2C6H4CFꢀCF2
p-MeOC6H4CFꢀCF2
o-(CH3)2CHC6H4CFꢀCF2
p-BrC6H4CFꢀCF2
m-CF3C6H4CFꢀCF2
o-FC6H4CFꢀCF2
65°C/1 h
65°C/2 h
a Isolated yield of pure styrene after column chromatography of the reaction mixture.
b All products gave satisfactory 19F, 1H, 13C NMR and HRMS data consistent with the assigned structure.
c No bis-styrene detected after 12 h/rt; ꢀ3% bis-styrene was formed after 24 h/rt.

R. Anilkumar, D. J. Burton / Tetrahedron Letters 43 (2002) 2731–2733
2733
3. (a) Cohen, S. G.; Wolosinski, H. T.; Scheuer, P. J. J. Am.
Chem. Soc. 1949, 71, 3439–3440; (b) Cohen, S. G.;
Wolosinski, H. T.; Scheuer, P. J. J. Am. Chem. Soc. 1950,
72, 3952–3953.
4. Prober, M. J. Am. Chem. Soc. 1953, 75, 968–973.
5. Dixon, S. J. Org. Chem. 1956, 21, 400–403; US Patent
2,874,197 1955.
14. (a) Banger, K. K.; Brisdon, A. K.; Gupta, A. Chem.
Commun. 1997, 139–140; (b) Banger, K. K.; Banham, R.
P.; Brisdon, A. K.; Cross, W. I.; Damant, G.; Parsons, S.;
Pritchard, R. G.; Sousa-Pedrares, A. J. Chem. Soc.,
Dalton Trans. 1999, 427–434.
15. (a) Gillet, J. P.; Sauvetre, R.; Normant, J. F. Synthesis
1986, 355–360; (b) Tellier, F.; Sauvetre, R.; Normant, J.
F.; Dromzee, U.; Jeannin, Y. J. Organomet. Chem. 1987,
331, 281–298.
6. McGrath, T. F.; Levine, R. J. Am. Chem. Soc. 1955, 77,
4168–4169.
16. The yield may slightly vary from reaction to reaction; this
yield was obtained in the typical experimental procedure
described in Ref. 17.
7. (a) Kazenikova, G. V.; Talalaeva, T. V.; Zimin, A. V.;
Simonov, A. P.; Kocheshov, K. A. Izv. Akad. Nauk
SSSR 1961, 1063; (b) Segree, N. M.; Shopeet’ko, N. N.;
Timoteyuk, G. V. Zh. Struekturn Khim. 1965, 6, 300; (c)
Petril, O. P.; Makhina, A. A.; Talalaeva, T. V.;
Kocheshov, K. A. Doklady Akad. Nauk SSSR 1966, 167,
594; (d) Hodgdon, R. B.; MacDonald, D. I. J. Polym.
Sci., Polym. Chem. Ed. 1968, 6, 711–717.
8. (a) Sigalov, A. B.; Beletskaya, I. P. Izv. Akad. Nauk
SSSR Ser. Khim. 1988, 445–450; (b) Nichols, L. D.;
Obermayer, A. S.; Panar, M. US Patent 3,449,449 1969.
9. (a) Shingu, H.; Hisazumi, M. US Patent 3,489,807 1970;
(b) Prober, M. US Patent 2,651,627 1953; (c) Prober, M.
US Patent 2,752,400 1956; (d) Hisazumi, M.; Shingu, H.
Nippon Kagaku Kaishi 1980, 1142–1147.
10. Sorokina, R. S.; Rybakova, L. F.; Kalinovskii, I. O.;
Beletskaya, I. P. Izv. Akad. Nauk SSSR, Ser. Khim. 1985,
1647–1649.
11. (a) Hansen, S. W.; Spawn, T. D.; Burton, D. J. J.
Fluorine Chem. 1987, 35, 415–420; (b) Burton, D. J.;
Hansen, S. W. J. Am. Chem. Soc. 1986, 108, 4229–4230.
12. (a) Heinze, P. L.; Burton, D. J. J. Fluorine Chem. 1986,
31, 115–119; (b) Heinze, P. L.; Burton, D. J. J. Org.
Chem. 1988, 53, 2714–2720.
17. Typical procedure: A 250 mL three-necked flask fitted
with a dry ice/isopropanol condenser, septum and a low
temperature thermometer was charged with anhydrous
ZnCl2 (3.42 g, 25 mmol) and THF (15 mL) under an N2
atmosphere. The suspension was cooled to 15°C and
HFC-134a (2.5 mL, 30 mmol) was condensed into the
slurry. Then, an LDA [generated from diisopropylamine
(7 mL, 50 mmol) and n-BuLi (20 mL, 2.5 M, 50 mmol) in
THF (25 mL) at 0°C] solution was added slowly (ꢀ35
min) through a cannula to the HFC-134a/ZnCl2 slurry
while keeping the temperature at 15–20°C (the tip of the
cannula was dipped into the THF to avoid decomposi-
tion of trifluorovinyllithium, formed by reaction of
gaseous HFC-134a with LDA, at the tip). The pale
yellow reaction mixture was stirred for 1 h and allowed to
warm to rt. The 19F NMR yield of the zinc reagent was
73%. The zinc reagent was concentrated to ꢀ half its
volume (40 mL), then 3.51 g (15 mmol) of p-MeOC6H4I
and 0.28 g (1.5 mol%) Pd(PPh3)4 were added to the
solution of the zinc reagent. The reaction mixture was
heated at 60°C/1 h, cooled, triturated several times with
hexanes, and the solvent was removed by rotoevapora-
tion. Silica gel column chromatography gave 2.29 g (12.2
mmol, 82%) of pure p-MeOC6H4CFꢀCF2. The spectro-
scopic data was in agreement with a sample prepared
previously in this laboratory.12b
13. (a) Burdon, J.; Coe, P. L.; Haslock, I. B.; Powell, R. L.
Chem. Commun. 1996, 49–50; (b) Burdon, J.; Coe, P. L.;
Haslock, I. B.; Powell, R. L. J. Fluorine Chem. 1997, 85,
151–153; (c) Burdon, J.; Coe, P. L.; Haslock, I. B.;
Powell, R. L. J. Fluorine Chem. 1999, 99, 127–131.