The trifluoromethylation of 1,1-dibromo-1-alkenes using trifluoromethylcopper (CF3Cu) generated in situ from methyl fluorosulfonyldifluoroacetate

Article abstract of DOI:10.1016/S0022-1139(01)00451-1

The trifluoromethylation of 2-aryl-1,1-dibromo-1-alkenes with CF₃Cu under palladium catalysis gave bistrifluoromethylated compounds (2), whereas under the same reaction conditions, monotrifluoromethylated products (3) were obtained exclusively

Full text of DOI:10.1016/S0022-1139(01)00451-1

Journal of Fluorine Chemistry 111 ꢀ2001) 185±187
The tri¯uoromethylation of 1,1-dibromo-1-alkenes using
tri¯uoromethylcopper ꢀCF3Cu) generated in situ from
methyl ¯uorosulfonyldi¯uoroacetate
Feng-Ling Qinga,b,*, Xingguo Zhangc, Yiyuan Pengc
aLaboratory of Organo¯uorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
bCollege of Chemistry and Chemical Engineering, Donghua University, 1882 West Yanan Lu, Shanghai 200051, China
cDepartment of Chemistry, Jiangxi Normal University, Jiangxi 330027, China
Received 25 March 2001; accepted 19 June 2001
Abstract
The tri¯uoromethylation of 2-aryl-1,1-dibromo-1-alkenes with CF3Cu under palladium catalysis gave bistri¯uoromethylated compounds
ꢀ2), whereas under the same reaction conditions, monotri¯uoromethylated products ꢀ3) were obtained exclusively in the case of 2-alkyl-1,1-
dibromo-1-alkenes. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Tri¯uoromethylation; 1,1-Dibromo-1-alkenes; Palladium catalysis
1. Introduction
2. Results and discussion
The introduction of the tri¯uoromethyl group into an
organic compound can bring about remarkable changes in
the physical, chemical and biological properties that result in
new compounds/materials making them suitable for diverse
applications in the areas of materials science, agrochemistry,
and biomedical chemistry [1,2]. While a wide variety of
methods have been developed for introducing tri¯uoro-
methyl groups into organic compounds [3,4], the coupling
reaction of alkene halides with in situ generated tri¯uoro-
methylcopper ꢀCF3Cu) is rapidly becoming the method of
choice [5]. 1,1-Dibromo-1-alkenes are easily prepared [6,7],
and are versatile in organic synthesis. They can form ꢀZ)-1-
arylꢀalkenyl)-1-bromo-1-alkenes, stereospeci®cally trisub-
stituted alkenes, disubstituted cis-1-bromo-1-alkenes, and
1,3-diynes through coupling with organoboronic acids [8,9],
organostannanes [10,11], organozinc and Grignard reagents
[12±14], tributyltin hydride [15] and alkynes [16]. Stimu-
lated by these ®ndings we were interested in the investiga-
tion of the tri¯uoromethylation of 1,1-dibromo-1-alkenes in
order to obtain a novel type of tri¯uoromethyl-containing
building blocks.
1,1-Dibromo-alkenes were prepared by the reaction of
aldehydes with triphenyl phosphorus and carbon tetrabro-
mide in dichloromethane [7]. 1,1-Dibromo-2-ꢀ4-nitrophe-
nyl)ethene ꢀ1a) was chosen as model substrate to couple
with in situ generated CF3Cu. First, the tri¯uoromethylation
of 1a was carried out using modi®ed Chen's methodology
[17,18]. Treatment of 1a with FSO2CF2CO2Me ꢀ5.0 eq.) and
CuI ꢀ0.3 eq.) in DMF/HMPA at 708C for 24 h gave a mixture
of bistri¯uomethylated compound ꢀ2a), monotri¯uoro-
methylated compounds ꢀE)-3a and ꢀZ)-3a, along with
unreacted 1a ꢀScheme 1). These compounds were very
dif®cult to separate. The ratio of 2a:ꢀE)-3a:ꢀZ)-3a was
2:1:1 as determined by 19F NMR. In an attempt to get a
single product and improve the reaction ef®ciency, we
examined the tri¯uoromethylation under palladium cataly-
sis. When 5 mol% PdCl2 was added to the reaction mixture
under similar reaction conditions, 1a was totally converted
and the ratio of 2a:ꢀE)-3a:ꢀZ)-3a was changed to 12:1:1.
When the PdCl2 was replaced by PdꢀPPh3)4, we were
pleased to ®nd that only a single bistri¯uomethylated com-
pound ꢀ2a) was isolated in 82% yield. These results showed
the addition of palladium catalyst greatly improved the
bistri¯uomethylation. 1,1-Bisꢀtri¯uoromethyl)alkenes have
been prepared from the reaction of aldehydes with 2,2-
dichlorohexa¯uoropropane [19] or tetrakisꢀtri¯uoromethyl)-
1,3-dithietane [20] in the presence of triphenyl phosphine.
* Corresponding author. Tel.: ‡86-21-64163300;
fax: ‡86-21-64166128.
E-mail address: flq@pub.sioc.ac.cn ꢀF.-L. Qing).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 4 5 1 - 1

186
F.-L. Qing et al. / Journal of Fluorine Chemistry 111 62001) 185±187
Scheme 1.
Scheme 2.
However, the tri¯uoromethyl-containing starting materials
are not readily accessible.
ꢀentries 4±6), monotri¯uoromethylated products ꢀ3) were
obtained exclusively instead of the bistri¯uoromethylated
compounds ꢀ2).
With these results in hand we next performed the tri-
¯uoromethylation reaction with a more extensive range of
1,1-dibromo-1-alkenes ꢀScheme 2 and Table 1). As shown in
Table 1, 2-aryl-1,1-dibromo-1-alkenes gave bistri¯uoro-
methylated compounds ꢀ2) in good yields, with no to small
amount of monotri¯uoromethylated products ꢀ3) isolated.
Substitutions at the para position of the aromatic ring by
the electron-donating methoxy group did not affect the
tri¯uoromethylation reaction ꢀentry 2). However, in the case
of 2-alkyl-1,1-dibromo-1-alkenes under reaction conditions
identical to those used for 2-aryl-1,1-dibromo-1-alkenes
3. Experimental section
1H NMR spectra were recorded on a 300 MHz spectro-
meter with Me4Si as internal standard. 19F NMR spectra
were obtained on a 56.4 MHz spectrometer using tri¯uor-
oacetic acid as external standard, down®eld shifts being
designated as negative. All chemical shifts ꢀd) are expressed
in ppm, coupling constants ꢀJ) are given in Hz. Mass spectra
Table 1
Trifluoromethylation of 1,1-dibromo-1-alkenes with in situ generated CF3Cu under PdꢀPPh3)4 catalysis
Entry
Dibromide
Product
Yield ꢀ%)a
82
1
2
3
76
55
b
b
4
5
6
90
82
60
b
a Yields were based on 1.
b The Z:E ratio was determined by 1H NMR.

F.-L. Qing et al. / Journal of Fluorine Chemistry 111 62001) 185±187
187
were recorded on a Finnigan-MAT-8430 instrument using
EI ionization at 70 eV. IR spectra were recorded on a
Shimadzu IR-440 spectrometer. 1,1-Dibromo-alkenes ꢀ1)
were prepared using the literature procedure [7].
ꢀ56.4 MHz, CDCl3): d À17.8 ꢀs, 1.83F), À10.6 ꢀs, 1.17F); IR
ꢀthin ®lm) 2984, 1709, 1378, 1175, 1155 cmÀ1; MS m/z 373
ꢀM , 5), 274 ꢀ43), 57 ꢀ100); anal. calcd for C13H19BrF3NO3:
C, 41.73; H, 5.12; N, 3.74. Found: C, 41.91; H, 5.28; N,
3.99%.
‡
3.1. Representative procedure for the trifluoromethylation
of 1,1-dibromo-alkenes 1
3.6. 1-Bromo-1-trifluoromethyl-2-[6S)-2,2-dimethyl-1,
3-dioxolan-4-yl]ethene 63e)
A solution of FSO2CF2CO2CH3 ꢀ1.3 ml, 10 mmol) in
DMF ꢀ5 ml) was added via syringe over a period of 1.5 h
to a mixture of dibromide ꢀ1a) ꢀ615 mg, 2 mmol), CuI
ꢀ115 mg, 0.6 mmol), PdꢀPPh3)4 ꢀ116 mg, 0.1 mmol) and
HMPA ꢀ1 ml) in DMF ꢀ10 ml) at 708C under a nitrogen
atmosphere. The reaction was stirred at 708C for 24 h before
being cooled to room temperature. Saturated aqueous
NH4Cl ꢀ30 ml) was added and the mixture was extracted
with ether. The extracts were washed with brine and dried
over Na2SO4. The solvent was removed in vacuo. Puri®ca-
tion of the residue by column chromatography on silica gel
and elution with 25:1 hexane ethyl acetate gave compounds
2a ꢀ469 mg, 82% yield).
1H NMR ꢀ300 MHz, CDCl3): d 6.86 ꢀd, J ˆ 7:5 Hz,
0.37H), 6.56 ꢀd, J ˆ 7:5 Hz, 0.63H), 5.04 À 4.90 ꢀm, 1H),
4.34 ꢀm, 0.37H), 4.18 ꢀm, 0.63H), 3.72 ꢀm, 1H), 1.48 À 1.36
ꢀm, 6H); 19F NMR ꢀ56.4 MHz, CDCl3): d À17.2 ꢀs, 1.89F),
À9.8 ꢀs, 1.11F); IR ꢀthin ®lm) 2992, 1374, 1179, 1149,
1066 cmÀ1; MS m/z 275 ꢀM ‡ 1, 15), 259 ꢀ73), 43 ꢀ100);
‡
anal. calcd for C8H10BrF3O2: C, 34.93; H, 6.67. Found: C,
34.99; H, 6.67%.
3.7. 1-Bromo-1-trifluoromethylnon-1-ene 63f)
1H NMR ꢀ300 MHz, CDCl3): d 6.70 ꢀt, J ˆ 7:0 Hz,
0.37H), 6.44 ꢀt, J ˆ 7:0 Hz, 0.63H), 3.72 ꢀm, 1H),
2.38 À 2.24 ꢀm, 2H), 1.54 À 1.26 ꢀm, 10H), 1.48 À 1.36
ꢀm, 6H), 0.89 ꢀt, J ˆ 7:0 Hz, 3H); 19F NMR ꢀ56.4 MHz,
CDCl3): d À17.2 ꢀs, 1.56F), À9.8 ꢀs, 1.44F); IR ꢀthin ®lm)
3.2. 1,1-Ditrifluoromethyl-2-64-nitrophenyl)ethene 62a)
1H NMR ꢀ300 MHz, CDCl3): d 8.32 ꢀd, J ˆ 8:7 Hz, 2H),
7.74 ꢀs, 1H), 7.55 ꢀd, J ˆ 8:7 Hz, 2H); 19F NMR ꢀ56.4 MHz,
CDCl3): d À20.8 ꢀs, 3F), À14.6 ꢀs, 3F); IR ꢀKBr) 2985,
‡
2959, 2930, 1289, 1172, 1143 cmÀ1; MS m/z 272 ꢀM , 15),
69 ꢀ61), 43 ꢀ100); anal. calcd for C10H16BrF3: C, 43.97; H,
5.90. Found: C, 43.72; H, 5.63%.
‡
1672, 1527, 1351, 1284, 1194, 1164 cmÀ1; MS m/z 285 ꢀM ,
94), 318 ꢀ100), 169 ꢀ96), 89 ꢀ11); anal. calcd for
C10H5F6NO2: C, 42.12; H, 1.77; N, 4.91. Found: C,
42.45; H, 1.94; N, 5.21%.
References
3.3. 1,1-Ditrifluoromethyl-2-64-methoxyphenyl)ethene 62b)
1H NMR ꢀ300 MHz, CDCl3): d 7.50 ꢀs, 1H), 7.48 ꢀd,
[1] J.T. Welch, Tetrahedron 43 ꢀ1987) 3123.
[2] I. Ojima, J.T. McCarthy ꢀEds.), Biomedical Frontiers of Fluorine
Chemistry; ACS Symposium Series 639, American Chemical
Society, Washington, DC, 1996.
J ˆ 8:9 Hz, 2H), 6.92 ꢀd, J ˆ 8:9 Hz, 2H), 3.80 ꢀs, 3H); 19
F
[3] G.A. Olah, G.K.S. Prakash, R.D. Chambers, Synthetic Fluorine
Chemistry, Wiley, New York, 1992.
NMR ꢀ56.4 MHz, CDCl3): d À19.8 ꢀs, 3F), À14.6 ꢀs, 3F); IR
ꢀthin ®lm) 2966, 1608, 1516, 1289, 1176, 1154 cmÀ1; MS m/
[4] G.G. Furin, Synthetic Aspects of the Fluorination of Organic
Compounds; Harwood, London, 1991.
‡
‡
z 271 ꢀM ‡ 1, 14), 270 ꢀM , 100); anal. calcd for
C11H8F6O: C, 48.90; H, 2.99. Found: C, 48.70; H, 2.96%.
[5] M.A. McClinton, D.A. McClinton, Tetrahedron 48 ꢀ1992) 6555.
[6] E.J. Corey, P.L. Fuches, Tetrahedron Lett. ꢀ1972) 3769.
[7] F. Ramirez, N.B. Desai, N. McKelvie, J. Am. Chem. Soc. 84 ꢀ1962)
1745.
3.4. 1,1-Ditrifluoromethyl-2-phenylethene 62c)
[8] W.R. Roush, K.J. Moriarty, B.B. Brown, Tetrahedron Lett. 31 ꢀ1990)
6509.
[9] W. Shen, Synlett ꢀ2000) 737.
1H NMR ꢀ300 MHz, CDCl3): d 7.74 À 7.20 ꢀm); 19F
NMR ꢀ56.4 MHz, CDCl3): d À17.6 ꢀs, 3F), À9.8 ꢀs, 3F);
IR ꢀthin ®lm) 3033, 1275, 1216, 1138 cmÀ1; MS m/z 241
[10] W. Shen, L. Wang, J. Org. Chem. 64 ꢀ1999) 8873.
[11] L. Wang, W. Shen, Tetrahedron Lett. 39 ꢀ1998) 7625.
[12] A. Minato, K. Suzuki, K. Tamao, J. Am. Chem. Soc. 109 ꢀ1987)
1257.
‡
‡
ꢀM ‡ 1, 12), 240 ꢀM , 100), 171 ꢀ28), 151 ꢀ74); HRMS
calcd for C10H6F6: C, 240.0337. Found: 240.0373.
[13] A. Minato, J. Org. Chem. 56 ꢀ1991) 4052.
[14] J.S. Panek, T. Hu, J. Org. Chem. 62 ꢀ1997) 4912.
[15] J. Uenishi, R. Kawahama, O. Yonemitsu, J. Tsuji, J. Org. Chem. 63
ꢀ1998) 8965.
3.5. 6Z)/6E)-tert-butyl 64S)-4-620-bromo-20-
trifluoromethyleth-10-enyl)-2,2-dimethoyyloxazolidine-
3-carboxylate 63d)
[16] W. Shen, S.A. Thomas, Org. Lett. 2 ꢀ2000) 2857.
[17] X. Zhang, F.L. Qing, Y. Yu, J. Org. Chem. 65 ꢀ2000) 7075.
[18] Q.Y. Chen, S.W. Wu, J. Chem. Soc., Chem. Commun. ꢀ1989) 705.
[19] M. Hanack, C. Korhummel, Synthesis ꢀ1987) 944.
[20] D.J. Burton, Y. Inouge, Tetrahedron Lett. ꢀ1976) 3397.
1H NMR ꢀ300 MHz, CDCl3): d 6.68 ꢀd, J ˆ 8:9 Hz,
0.39H), 6.46 ꢀd, J ˆ 8:9 Hz, 0.61H), 4.84 ꢀm, 1H), 4.12
ꢀm, 1H), 3.78 ꢀm, 1H), 1.74 À 1.38 ꢀm, 15H); 19F NMR