Tetrahedron Letters
Preparation of (2,2-difluoroethenylidene)bis(tributylstannane) and arylation
reaction: efficient approach to 1,1-diaryl-2,2-difluoroethenes
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Seung Yeon Han, Hyo Young Lee, Jong Hee Jeon, In Howa Jeong
Department of Chemistry and Medical Chemistry, Yonsei University, Wonju, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of 2,2-difluoro-1-tributylstannylethenyl p-toluenesulfonate (1) with bis(tributyltin) in the pres-
ence of 5 mol % Pd(PPh3)4 and 30 equiv LiBr in THF at reflux temperature for 7 h afforded (2,2-difluoro-
ethenylidene)bis(tributylstannane) (2) in a 70% yield. Coupling reaction of 2 with aryl iodides in the
presence of 5 mol % Pd(PPh3)4 and 5 mol % CuI in DMF at 80 °C for 3–4 h provided the coupled products
3 in 59–85% yields.
Received 8 December 2011
Revised 28 January 2012
Accepted 30 January 2012
Available online 6 February 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
(2,2-Difluoroethenylidene)-
bis(tributylstannane)
Arylation reaction
2,2-Diaryl-1,1-difluoroethenes
2,2-Disubstituted 1,1-difluoroethenes are an important class of
fluoroorganic compounds with unique chemical1 and biological
properties.2 They undergo an addition–elimination reaction to-
ward nucleophiles3 to give the corresponding 1,2,2-trisubstituted
1-fluoroethenes, in which 2,2-disubstituted 1-fluoroethenes are
potential mechanism-based inhibitors,4 and are known to act as
a bioisostere for the disubstituted ketones.5 Among these com-
pounds, 1,1-diaryl-2,2-difluoroethenes are of special interest, due
to their potential utility as enzyme inhibitors and pesticides.6
The synthesis of 1,1-diaryl-2,2-difluoroethenes can be achieved
by the Wittig-type reaction, the use of 2,2-difluoroethenylmetal
reagents as building blocks and other methods. However, the Wit-
tig-type reaction was not suitable due to the poor reactivity of the
diaryl ketones toward the difluoromethylene ylide.7 Other method
also gave a specific 1,1-difluoro-2,2-diphenylethene.8 The use of
2,2-difluoethenylmetal reagents provided one straightforward
route to 1,1-diaryl-2,2-difluoroethenes. Burton et al. reported a
general and efficient method for the synthesis of 1,1-diaryl-2,2-
couple of advantages as compared to the other methods, such as
relatively simple procedure and easy handling of reagents. How-
ever, this method still has some drawbacks such as the lack of gen-
erality due to the use of arylstannane reagents as a coupling
partner.11 To overcome this disadvantage, we decided to introduce
two tributylstannanyl groups at the same vinylidene carbon and
such a compound has not been reported, although synthesis of
(E)-(1,2-difluoroethenylidene)bis(tributylstannane)12 and its syn-
thetic application13 have been previously studied. Herein, we first
report the method for the preparation of (2,2-difluoroethenylid-
ene)bis(tributylstannane) and its arylation reaction. (2,2-Difluoro-
ethenylidene)bis (tributylstannane) (2) could be a remarkable
precursor of 2,2-diaryl-1,1-difluoroethenes (3) because it has two
functionally same coupling partners at the same position such as
the nucleophilic tributylstannyl groups.
2,2-Difluoro-1-tributylstannylethenyl p-toluenesulfonate (1)
was easily prepared in a 90% yield from the reaction of 2,2,2-
trifluoroethyl p-toluenesulfonate with 2 equiv of LDA in THF at
À78 °C, followed by treatment with tributylstannyl chloride.11
Then, we attempted the stannanylation reaction of 1 with bis(tri-
butyltin) in the presence of catalytic amount of Pd(PPh3)4 and
excess of LiBr to introduce a stannanyl group at the tosylate site.
When 1 was reacted with bis(tributyltin) in the presence of
5 mol % Pd(PPh3)4 and 3 equiv of LiCl in THF at reflux temperature
for 24 h, the desired product 2 was obtained along with reduction
product 4 (GC ratio of 2:4 = 25:75). It is postulated that the forma-
tion of 4 could be derived from the protonation of vinyl palladium
(II) complex, possible intermediate in this stannylation reaction,
via quenching with water. The same reaction was performed in
the presence of 3 equiv of LiBr instead of LiCl to give 2 in higher
difluoroethenes, in which
the coupling reaction of the corresponding
a
-halo-b,b-difluorostyrenes formed by
-halo-b,b-difluoro-
a
ethenylzinc reagents with aryl iodides were functionalized at the
halogen site via Suzuki–Miyaura coupling reactions.9 1,1-
Diaryl-2,2-difluoroethenes can be also prepared from the Pd(0)/
CuI-catalyzed coupling reaction of b,b-difluoro-a-phenylvinylst-
annane with aryl iodides.10 Recently, consecutive cross-coupling
reactions of 2,2-difluoro-1-tributylstannylethenyl p-toluenesulfo-
nate afforded 1,1-diaryl-2,2-difluoroethenes. This method has a
⇑
Corresponding author. Tel.: +82 33 760 2240; fax: +82 33 763 4323.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.