Note
DOI: 10.1002/bkcs.11419
BULLETIN OF THE
Y. H. Jin et al.
KOREAN CHEMICAL SOCIETY
Cross-Coupling Reactions of (Z)-2-Fluoro-2-trifluoromethylethenyl
Tosylate with Aryl- and Arylethenylboronic Acids
*
Yeong Hyun Jin, Seo Hee Lee, Sung Lan Jeon, and In Howa Jeong
Department of Chemistry and Medical Chemistry, Yonsei University, Wonju 220-710, South Korea.
*E-mail: jeongih@yonsei.ac.kr
Received October 31, 2017, Accepted February 6, 2018, Published online March 23, 2018
Keywords: Cross-coupling reaction, (Z)-2-Fluoro-2-trifluoromethylethenyl tosylate, Arylboronic acids,
Arylethenylboronic acids
Organofluorine compounds have received much attention in
medicinal, agricultural, and material sciences because they
often confer dramatic changes in their chemical, physical,
and biological properties.1–3 Especially, compounds con-
taining trifluoromethyl group have been widely applied in
drug development because of their unique property for the
high cross ability of the cell membrane.4–6 Therefore, intro-
duction of a trifluoromethyl group into the organic mole-
cules has been an important subject in recent years.7–11
Although methods for the trifluoromethylation involving a
direct coupling reaction of trifluoromethylated metal
reagents with aryl- or alkenyl halides have been well estab-
lished in recent years,12–14 these methods suffer from low
reactivity and low selectivity. An alternative promising
approach is to use trifluoromethylated building blocks
which can be easily prepared from the commercially avail-
able starting materials. In our continuing efforts to explore
the preparation of trifluoromethylated alkenes, we are inter-
ested in the highly stereoselective preparation of trifluoro-
methylated alkenes by cross-coupling reaction of the
organometallic reagents with the corresponding stereo-
controlled trifluoromethylated alkene. Recently, we estab-
lished the effective cross-coupling reactions between
several 2,2-difluoroethenyl tosylate derivatives having two
fluorine atoms at the one carbon atom of the double bond
and organometallic reagents, in which direct cross-coupling
reaction of tosyl group with arylstannane reagents15,16 or
arylboronic acids,17 and transformation of tosyl group to
stannane group18,19 for the Stille cross-coupling reactions
were described. We will extend this study to the cross-
coupling reaction of trifluoromethylated alkenyl tosylate.
Since trifluoromethylated ethenyl system is totally different
from 1,1-difluorinated ethenyl one from the electronic dis-
tribution point of view, examination of this coupling reac-
tion will be valuable. The only one case of
trifluoromethylated alkenyl tosylate was reported by Funa-
biki et al. who prepared the highly (Z)-stereoselective 2-
fluoro-2-trifluoromethylethenyl tosylate and then carried
out reactions with a variety of electrophiles after in situ
generation of the corresponding perfluoroethenyllithium
reagent.20 However, the direct cross-coupling reaction of
(Z)-2-fluoro-2-trifluoromethylethenyl tosylate with organo-
metallic reagents has not been studied and also their prod-
ucts have not been easily prepared by the previous
methods.21–23 Herein, we wish to report the general and
efficient preparation of highly stereoselective (Z)-(2,3,3,3-
tetrafluoroprop-1-enyl)benzenes and (Z,E)-4-aryl-1-fluoro-
1-trifluoromethylbuta-1,3-dienes via the cross-coupling
reactions of (Z)-2-fluoro-2-trifluoromethylethenyl tosylate
with aryl- and arylethenylboronic acids.
Starting material, the highly (Z)-stereoselective 2-fluoro-
2-trifluoromethylethenyl tosylate (1) (Z:E = 98:2) was pre-
pared by the previous procedure.20 Then, we first examined
the reactivity of 1 with tributylphenylstannane in the pres-
ence of Pd(PPh3)4 (5 mol %) and LiBr (3 equiv) in DMF at
100ꢀC for 2 h, which condition was performed for the prep-
aration of 1,1-diaryl-2,2-difluoroethenes,15 but the reaction
did not proceed at all. Then, we changed the organometallic
reagent to less toxic phenylboronic acid. When 1 was trea-
ted with phenylboronic acid (2.0 equiv) in the presence of
Pd(PPh3)2Cl2 (5 mol %) and Cs2CO3 (1.7 equiv) in MeOH
at room temperature for 12 h, the desired product 2a was
not observed at all. The use of Pd catalysts such as
Pd(OAc)2 or Pd2(dba)3 in the same reaction did not provide
the desired product, either. However, treatment of 1 with
phenylboronic acid (2.0 equiv) in the presence of Pd(OAc)2
(2 mol %), PCy3 (4 mol %) and Cs2CO3(1.7 equiv) in a
mixture of dioxane and water (20:1) at 100ꢀC for 4 h
resulted in the formation of coupled product 2a in 23%
yield based on the conversion of starting material. This
result indicated that the use of bulky ligand such as PCy3
and the use of H2O as a co-solvent caused to proceed the
coupling reaction. However, the bulky ligand such as X-
Phos was not effective in this reaction. The use of K3PO4
as a base in the same reaction caused to increase the yield
2a up to 32% yield. More addition of the mol % of
Pd(OAc)2 and PCy3 resulted in the increase in the yield of
2a. Finally, when 1 was reacted with phenylboronic acid
(2.0 equiv) in the presence of Pd(OAc)2 (10 mol %), PCy3
(20 mol %) and K3PO4(1.7 equiv) in a mixture of dioxane
and water (20:1) at 100ꢀC for 4 h, the desired product 2a
was obtained in 80% yield. The use of less amount of
Bull. Korean Chem. Soc. 2018, Vol. 39, 567–570
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
567