Preparation of novel β,β-diphenyl α-(trifluoromethyl)vinylstannane and its cross-coupling reactions with aryl iodides

Article abstract of DOI:10.1016/S0040-4039(00)01606-3

β,β-Diphenyl-α-(trifluoromethyl)vinylstannane 6 was prepared in good yield via several steps from 2,3,3,3-tetrafluoro-1-phenyl-1-phenylthiopropene. The cross-coupling reactions of 6 with aryl iodides in the presence of a catalytic amount of Pd(PPh₃)₄ and CuI provided trifluoromethylated triphenylethene derivatives 7 in high yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01606-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8917–8921
Preparation of novel b,b-diphenyl
a-(trifluoromethyl)vinylstannane and its cross-coupling
reactions with aryl iodides
In Howa Jeong,a,* Young Sam Parka and Bum Tae Kimb
aDepartment of Chemistry, Yonsei University, Wonju 220-710, South Korea
bKorea Research Institute of Chemical Technology, Daejeon 305-606, South Korea
Received 16 August 2000; revised 13 September 2000; accepted 14 September 2000
Abstract
b,b-Diphenyl-a-(trifluoromethyl)vinylstannane 6 was prepared in good yield via several steps from
2,3,3,3-tetrafluoro-1-phenyl-1-phenylthiopropene. The cross-coupling reactions of 6 with aryl iodides in
the presence of a catalytic amount of Pd(PPh3)4 and CuI provided trifluoromethylated triphenylethene
derivatives 7 in high yields. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: b,b-diphenyl-a-(trifluoromethyl)vinylstannane; cross-coupling reactions.
The introduction of a trifluoromethyl (CF3) functionality into organic molecules is an
important subject in organofluorine chemistry because some of the resultant compounds exhibit
unique properties in the areas of agrochemicals, pharmaceuticals and material science.1
Although direct trifluoromethylation2 and halogen-exchange reaction3 have been widely utilized
to construct trifluoromethylated compounds, a promise alternative approach is to use trifl-
uoromethylated building blocks.4 Of particular interests in this conjunction is b,b-diphenyl
a-(trifluoromethyl)vinylstannane, which is a quite useful building block for the synthesis of
trifluoromethylated triphenylethene derivatives. It has been well known that triphenylethene
unit5 is the important framework of many nonsteroidal antiestrogens which exhibit mammary
tumor inhibiting properties via binding to the estrogen receptor. In particular, trifluoromethyl-
analogs have received much attention in recent years because of enhancement of biological
property.6 Although a-(trifluoromethyl)vinylmetal reagents bearing proton, fluorine or ethoxy
groups at b-position have been synthesized via previous methods, however, methodology for the
preparation of a-(trifluoromethyl)vinylmetal reagents bearing two phenyl groups at b-position
has not been exploited previously. Generally, a-(trifluoromethyl)vinyllithium reagents7 are quite
* Corresponding author. Fax: 82-33-763-4323; e-mail: jeongih@dragon.yonsei.ac.kr
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01606-3

8918
unstable even at low temperature, in which difluoroallene was formed via defluorination of
a-(trifluoromethyl)vinyllithium. However, b,b-difluoro-a-(trifluoromethyl)vinyllithium8 can be
prepared from the reaction of 2-hydropentafluoropropene with LDA or t-BuLi at −78°C. Jiang
prepared a stable a-(trifluoromethyl)vinylzinc reagent9 from the reaction of 2-bromotrifluoro-
propene with Zn(Ag) in the presence of TMEDA. The coupling reactions of a-(trifluoromethyl)-
vinylzinc reagent with aryl and vinyl halides have been quite successful,9,10 but
a-(trifluoromethyl)vinylzinc reagent failed to react with acyl chlorides in the presence of
palladium catalyst.9 a-(Trifluoromethyl)vinylzinc reagents bearing fluorine11 or ethoxy group12 at
b-position were also prepared in a similar manner and their coupling reactions with aryl halides
afforded the corresponding a-trifluoromethylated compounds. Recently, a-(trifl-
uoromethyl)vinylstannane reagents bearing only hydrogens at b-position have been prepared
from the reaction of 2-bromotrifluoroisopropene with lithium tributylstannate in the presence of
CuI and utilized for the cross-coupling with acyl halides to give a-(trifluoromethyl)vinyl
ketones.13 However, there is no report on the coupling reaction of a-(trifl-
uoromethyl)vinylstannane with aryl halides. Thus, we wish to describe a new and efficient
method for the preparation of novel b,b-diphenyl-a-(trifluoromethyl)vinylstannane reagent and
cross coupling reactions with aryl iodides to give trifluoromethylated triphenylethene derivatives
in this communication.
A novel starting material, b,b-diphenyl-a-(trifluoromethyl)vinylstannane reagent, was pre-
pared via several steps from 2,3,3,3-tetrafluoro-1-phenyl-1-phenylthiopropene (1).14 Oxidation of
1 with mCPBA (2.5 equiv.) in CH2Cl2 at reflux temperature for 24 hours afforded 2,3,3,3-tetra-
fluoro-1-phenyl-1-phenylsulfonylpropene (2)15 in 92% yield. Treatment of 2 with sodium thio-
phenoxide (4 equiv.) in toluene at 0°C for 24 hours resulted in the formation of
3,3,3-trifluoro-1-phenyl-1-phenylsulfonyl-2-phenylthiopropene (3)15 in 81% yield. The choice of
solvent and reaction temperature are quite important to give 3 in this reaction. The use of
solvents, such as THF, CH3CN or DMF, or elevated reaction temperature caused the formation
of a significant amount of 1,2-bis(phenylthio)-3,3,3-trifluoro-1-phenylpropene. When 3 was
reacted with phenyllithium (1.5 equiv.) in toluene at −78°C for 24 hours, 3,3,3-trifluoro-1,1-
diphenyl-2-phenylthiopropene (4)15 was obtained in 82% yield. Oxidation of 4 with mCPBA (2.5
equiv.) in CH2Cl2 at reflux temperature for 24 hours provided 3,3,3-trifluoro-1,1-diphenyl-2-
phenylsulfonylpropene (5)15 in 94% yield. Finally, b,b-diphenyl-a-(trifluoromethyl)vinylstannane
(6)15 reagent can be obtained in 84% yield by treatment of 5 with Bu3SnH (1.5 equiv.)/AIBN (10
mol%) in benzene at reflux temperature for 24 hours. The reducing product, 3,3,3-trifluoro-1,1-
diphenylpropene, was obtained in less than 5% yield (Scheme 1).
Since the vinylstannane group is an excellent functionality for carbonꢀcarbon bond formation
with electrophiles in the presence of palladium catalyst,16 we examined the reaction of 6 with
aryl iodides bearing a substituent on benzene ring in the presence of several palladium catalysts.
The use of a Pd catalyst such as Pd(PPh3)4 or Pd(PPh3)2Cl2 in THF, DMF, toluene or HMPA
did not provide any cross-coupling product. However, the cross-coupling reaction was well
proceeded by using a mixture of 10 mol% Pd(PPh3)4 and 10 mol% CuI in DMF. The reaction
was completed in 4 hours at room temperature. Aryl bromides did not provide a cross-coupling
adduct even at 80°C. Therefore, aryl iodides bearing a bromo, methoxy, methyl, nitro or
trifluoromethyl on para- or meta-position of benzene ring underwent the cross-coupling reaction
with 6 in the presence of 10 mol% Pd(PPh3)4 and 10 mol% CuI in DMF at room temperature
for 4 hours, and the corresponding coupling products were obtained in high yields. Unfortu-
nately, the coupling product, formed from the reaction of 6 with aryl iodides bearing a methoxy

8919
Scheme 1.
or methyl on ortho-position of benzene ring, was obtained in less than 5% yield under the same
reaction conditions, whereas a reducing product and dimerization product (butadiene) were
formed as major products. The heating of the reaction mixture at 80°C resulted in the formation
of a messy reaction mixture. The experimental results are summarized in Table 1.
Table 1
The cross-coupling reactions of 6 with aryl iodides
Compound no.
X
Yield (%)a
7a
7b
7c
7d
7e
7f
7g
7h
7i
H
p-Br
93
86
89
88
93
90
88
80
81
82
85
B5
B5
p-OCH3
p-CH3
p-NO2
p-CF3
m-Br
m-OCH3
m-CH3
m-NO2
m-CF3
o-CH3
o-OCH3
7j
7k
7l
7m
a Isolated yields.

8920
A typical reaction procedure for the preparation of 7c is as follows. To a DMF (5 ml) solution
of p-iodoanisole (0.066 g, 0.28 mmol) and b,b-diphenyl-a-(trifluoromethyl)vinylstannane (0.118
g, 0.22 mmol) was added Pd(PPh3)4 (10 mol%) and CuI (10 mol%), and the reaction mixture was
stirred at room temperature for 4 hours under an argon atmosphere. After the reaction mixture
was quenched with water and then washed with 5% KF solution and brine, the solution was
extracted with ether twice. The ether solution was dried and chromatographed on a SiO2
column. Elution with a mixture of hexane and ethyl acetate (20:1) provided 0.069 g of
3,3,3-trifluoro-2-(4%-methoxy)phenyl-1,1-diphenylpropene 7c in 89% yield. Compound 7c: mp
1
67–68°C; H NMR (CDCl3) l 7.84–6.69 (m, 14H), 3.75 (s, 3H); 19F NMR (CDCl3) l −56.47 (s,
3F); MS, m/z (relative intensity) 354 (M+, 100), 285(7), 270(11), 241(8), 165(5), 126(3), 120(3),
51(3); IR (KBr) 3058, 2926, 2853, 1733, 1661, 1608, 1511, 1445, 1328, 1250, 1226, 1170, 1111,
1033, 983, 824, 757, 701, 640 cm−1.
Acknowledgements
This work was supported by Korea Research Foundation Grant (KRF-1999-015-DP0218).
References
1. (a) Welch. J. T.; Eswarakrishnan, S. In Fluorine in Bioorganic Chemistry; John Wiley & Sons: New York, 1991.
(b) Organofluorine Chemistry—Principle and Commercial Applications; Bank, R. E.; Smart, B. E.; Tatlow, J. C.,
Eds.; Plenum: New York, 1994.
2. (a) McClinton, M. A.; McClinton, D. A. Tetrahedron 1992, 48, 6555–6666. (b) Prakash, G. K. S.; Yudin, A. K.
Chem. Rev. 1997, 97, 757–786. (c) Singh, R. P.; Kirchmeier, R. L.; Shreeve, J. M. J. Org. Chem. 1999, 64,
2579–2581.
3. (a) Bloodworth, A. J.; Bowyer, K. J.; Mitchell, J. C. Tetrahedron Lett. 1987, 28, 5347–5350. (b) Riera, J.;
Castaner, J.; Carilla, J.; Robert, A. Tetrahedron Lett. 1989, 30, 3825–3828. (c) Castaner, J.; Riera, J.; Carilla, J.;
Robert, A.; Molins, E.; Miravitlles, C. J. Org. Chem. 1991, 56, 103–110.
4. (a) Derstine, C. W.; Smith, D. N.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1996, 118, 8485–8486. (b) Qing,
F. L.; Zhang, Y. Tetrahedron Lett. 1997, 38, 6729–6732. (c) Komatsu, Y.; Sakamoto, T.; Kitazume, T. J. Org.
Chem. 1999, 64, 8369–8374.
5. Desombre, E. R.; Mease, R. C.; Sanghavi, J.; Singh, T.; Seevers, R. H.; Hughes, A. J. Steroid Biochem. 1988, 29,
583–590.
6. Nemeth, G.; Dezsofi, R. K.; Lax, G.; Simig, G. Tetrahedron 1996, 52, 12821–12830.
7. Drakesmith, F. G.; Stewart, O. J.; Tarrant, P. J. Org. Chem. 1967, 33, 280–285.
8. Morken, P. A.; Lu, H.; Nakamura, A.; Burton, D. J. Tetrahedron Lett. 1991, 32, 4271–4274.
9. Jiang, B.; Xu, Y. J. Org. Chem. 1991, 56, 7336–7340.
10. Jiang, B.; Xu, Y. Tetrahedron Lett. 1992, 33, 511–514.
11. Morken, P. A.; Burton, D. J. J. Org. Chem. 1993, 58, 1167–1172.
12. Shi, G.-Q.; Huang, X.-H.; Hong, F. J. Org. Chem. 1996, 61, 3200–3204.
13. (a) Xu, Y.; Jin, F.; Huang, W. J. Org. Chem. 1994, 59, 2633–2641. (b) Ichikawa, J.; Fujiwara, M.; Okauchi, T.;
Minami, T. Synlett 1999, 927–929.
14. Jeong, I. H.; Min, Y. K.; Kim, Y. S.; Kim, B. T.; Cho, K. Y. Tetrahedron Lett. 1994, 35, 7783–7784.
1
15. Compound 2: mp 104–106°C; H NMR (CDCl3) l 7.65–7.01 (m, 10H); 19F NMR (CDCl3) l −62.49 (d, J=4.2
Hz, 3F, one isomer), −66.25 (d, J=4.2 Hz, 3F, other isomer), −102.16 (q, J=4.2 Hz, 1F, one isomer), −108.77
(q, J=4.2 Hz, 1F, other isomer); MS, m/z (relative intensity) 330 (M+, 48), 266(5), 189(53), 169(100), 125(52),
77(47), 51(33); IR (KBr) 3065, 1652, 1447, 1347, 1306, 1196, 1156, 1118, 1088, 761, 696, 605 cm−1. Compound
1
3: mp 94–96°C; H NMR (CDCl3) l 7.90–6.85 (m, 15H); 19F NMR (CDCl3) l −53.58 (s, 3F, one isomer), −54.50

8921
(s, 3F, other isomer); MS, m/z (relative intensity) 420 (M+, 17), 239(100), 210(78), 186(67), 109(77), 77(72), 65(42),
51(38); IR (KBr) 3061, 2962, 2924, 1726, 1581, 1476, 1445, 1326, 1260, 1146, 1084, 1024, 811, 753, 727, 689, 575
1
cm−1. Compound 4: mp 68–70°C; H NMR (CDCl3) l 7.37–7.02 (m, 15H); 19F NMR (CDCl3) l −56.22 (s, 3F);
MS, m/z (relative intensity) 356 (M+, 100), 287(52), 254(19), 239(25), 227(25), 210(27), 178(30), 165(34), 152(10),
109(8), 77(23); IR (KBr) 3059, 2926, 2854, 1582, 1491, 1443, 1293, 1253, 1184, 1147, 1122, 1033, 991, 742, 699,
1
637 cm−1. Compound 5: mp 111–113°C; H NMR (CDCl3) l 7.60–6.97 (m, 15H); 19F NMR (CDCl3) l −52.14
(s, 3F); MS, m/z (relative intensity) 388 (M+, 10), 246(100), 227(48), 178(25), 165(10), 125(17), 77(57), 51(34); IR
(KBr) 3062, 3030, 1583, 1449, 1323, 1294, 1247, 1192, 1154, 1083, 998, 759, 735, 687, 580 cm−1. Compound 6:
1
oil; H NMR (CDCl3) l 7.34–7.12 (m, 10H), 1.53–0.59 (m, 27H); 19F NMR (CDCl3) l −49.47 (s, 3F); MS, m/z
(relative intensity) 481 (M+−56, 4), 210(16), 209(100), 207(12), 189(11), 183(9), 177(5), 139(3), 57(6); IR (KBr)
3058, 3025, 2957, 2924, 2854, 2362, 2342, 1491, 1445, 1243, 1170, 1126, 1074, 764, 699 cm−1
.
16. Stille, J. K. Pure Appl. Chem. 1985, 57, 1771–1780.
.