Oxidative Heck Reaction of Fluorinated Olefins with Arylboronic Acids by Palladium Catalysis

Article abstract of DOI:10.1002/ejoc.201500597

The palladium-catalyzed oxidative Heck reaction of 2,3,3,3-tetrafluoroprop-1-ene with various arylboronic acids was explored for the first time. This method provides a direct route to access (Z)-β-fluoro-β-(trifluoromethyl)styrenes with high stereoselectivity.

Full text of DOI:10.1002/ejoc.201500597

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201500597
Oxidative Heck Reaction of Fluorinated Olefins with Arylboronic Acids by
Palladium Catalysis
Yang Li,[a,b] Dong-Huai Tu,[a] Yu-Jie Gu,[a] Bo Wang,[a] Yao-Yu Wang,[b] Zhao-Tie Liu,*[c]
Zhong-Wen Liu,[c] and Jian Lu*[a]
Keywords: Homogeneous catalysis / Oxidation / Stereoselectivity / Palladium / Alkenes
The palladium-catalyzed oxidative Heck reaction of 2,3,3,3-
tetrafluoroprop-1-ene with various arylboronic acids was ex-
plored for the first time. This method provides a direct route
to access (Z)-β-fluoro-β-(trifluoromethyl)styrenes with high
stereoselectivity.
Introduction
Fluorinated compounds have played an important role
in the fields of pharmaceutical science, agrochemistry, and
materials science.[1,2] Significant efforts have been made to
incorporate fluorinated groups into organic compounds.
The Heck reaction between aryl halides and fluorinated
olefins is a direct and atom-economic way to introduce
fluoro groups. Progress has been made in this field, with
several notable examples coming from some scientific re-
search groups.[3,4] Arylboronic acid derivatives are an im-
portant class of compounds for coupling reactions, which
are stable in air and to moisture, and they are compatible
with a broad range of common functional groups.[5] The
oxidative Heck reaction of arylboronic acids with common
olefins has been disclosed by Xiao,[6] Genet (Scheme 1),[7]
Larhed,[8] Jung,[9] and others.[10] However, to the best of our
knowledge, the oxidative Heck reaction of arylboronic acids
with fluorinated olefins has not been reported. On the basis
of our previous oxidative Heck reaction,[11] herein, we pres-
ent the first examples of the oxidative Heck reaction of vari-
ous arylboronic acids with a fluorinated olefin under Pd
catalysis.
Scheme 1. Palladium-catalyzed oxidative Heck reaction.
Conjugated aromatic systems with trifluoromethyl
groups such as β-(trifluoromethyl)styrene derivatives have
found wide use in organic light-emitting diodes and in other
applications of materials chemistry,[12] such as in the or-
ganofluorine material of dipiperidinobenzene, which is a
highly emissive fluorophore in solid states, such as in crys-
tals and thin films (Figure 1). The synthesis of these com-
pounds was difficult in the past.[13] For example, the synthe-
sis of (Z)-β-fluoro-β-(trifluoromethyl)styrenes required
two-step reactions.[14] Very recently, Nicholls[15] reported a
method to prepare (Z)-β-fluoro-β-(trifluoromethyl)styrenes
in (trifluoromethyl)acrylic acid by palladium-catalyzed vin-
yltrifluoromethylation of aryl halides through decarb-
[a] Department of Catalyst, Xi’an Modern Chemistry Research
Institute,
Xi’an 710065, P. R. China
E-mail: lujian204@263.net
http://www.mcri204.com.cn
[b] Key Laboratory of Synthetic and Natural Functional Molecule
Chemistry of the Ministry of Education, College of Chemistry
and Materials Science, Northwest University,
Xi’an 710069, P. R. China
[c] Key Laboratory of Applied Surface and Colloid Chemistry,
Ministry of Education, School of Chemistry and Chemical
Engineering, Shaanxi Normal University,
Xi’an 710119, P. R. China
E-mail: ztliu@snnu.edu.cn
http://www.snnu.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500597.
Figure 1. Structure of an organofluorine material.
4340
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4340–4343

Oxidative Heck Reaction of Fluorinated Olefins
oxylative cross-coupling. We envisioned that the reaction of yields of the products (Table 1. entries 6–10). Further, we
arylboronic acids with 2,3,3,3-tetrafluoroprop-1-ene, which studied the influence of base on the coupling reaction and
is a commercially available reagent, could be performed in found that NaHCO3 was the best choice for the reaction
a single step.
(Table 1, entries 11–14). Moreover, if 1,4-dioxane was se-
lected as the reaction solvent, 3a was obtained in 66% yield
with a Z/E ratio Ͼ99:1, as determined by 19F NMR spec-
troscopy, and the Z isomer was obtained as the major prod-
uct (Table 1, entry 15). Finally, we also investigated the ef-
fect of varying the catalyst loading. Increasing the loading
of Pd(PhCN)2Cl2 and PCy3 to 5 and 10 mol-%, respectively,
resulted in the formation of 3a in an excellent yield of 89%
(Table 1, entry 16). On the basis of this condition, we re-
duced the volume of 2 to 5 mmol with 5 mol-% catalyst. To
our surprise, the yield decreased to 22% (Table 1, entry 17).
Hence, the optimized reaction conditions involved the fol-
lowing: Pd(PhCN)2Cl2 (5 mol-%), PCy3 (10 mol-%), BPO
(2 equiv.), NaHCO3 (2 equiv.), and 1,4-dioxane at 110 °C
for 14 h. To explore the scope of the coupling reaction, vari-
ous arylboronic acids were then examined with 2 by using
Pd(PhCN)2Cl2/PCy3 as the catalyst and NaHCO3 as the
base. The results are summarized in Table 2. para-Substi-
tuted phenylboronic acids reacted smoothly with 2 to afford
the products in good to excellent yields (Table 2, entries 1–
10). In general, the yields of the reactions of arylboronic
acids with electron-donating groups were higher than those
of arylboronic acids with electron-withdrawing groups. For
instance, the yield of 3a was significantly higher than that
of 3h. Substrates having meta or ortho substituents also af-
forded products in satisfactory yields (Table 2, entries 11–
13). Trisubstituted arylboronic acids were also tested, and
the corresponding products were formed in good yields
(Table 2, entries 14–17). The substrate scope was extended
to target compounds with tetrasubstituted substrates such
as (2,4,6-trimethylphenyl)boronic acid, which afforded the
desired product in 52% yield (Table 2, entry 18). 4-Biphen-
ylboronic acid was also tested for the coupling reaction: it
performed the same as other para-substituted groups and
afforded the desired product in acceptable yield (Table 2,
entry 19). Furthermore, a carbazole-derived boronic acid
was also converted into the corresponding product in mod-
erate yield (Table 2, entry 20). Notably, the yield was low
due to the high volatility of the product.
Results and Discussion
We initially chose (4-methoxyphenyl)boronic acid (1a) as
a substrate for the screening of this coupling transforma-
tion. A solution of (4-methoxyphenyl)boronic acid (1a) and
2,3,3,3-tetrafluoroprop-1-ene (2) in DMF was stirred in the
presence of Pd(PPh3)2Cl2 (3 mol-%) as a catalyst, PCy3
(6 mol-%, Cy = cyclohexyl) as an additive, and benzoyl per-
oxide (BPO, 2 mmol) as an oxidant. Only (Z)-β-fluoro-β-
(trifluoromethyl)styrene (3a) was formed in a low yield of
18%, albeit with a high Z/E ratio (Table 1, entry 1).
Table 1. Optimization of the palladium-catalyzed coupling of aryl-
boronic acids with 2,3,3,3-tetrafluoroprop-1-ene.[a]
Entry Catalyst
Ligand
Base
Yield [%][b] Z/E ratio[c]
1
Pd(PPh3)2Cl2
PCy3
PCy3
–
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
18
0
0
99:1
99:1
–
2
–
3
4
Pd(PPh3)2Cl2
Pd(PPh3)4
PCy3
7
–
5
6
7
8
Pd(MeCN)2Cl2 PCy3
Pd(PhCN)2Cl2 PCy3
Pd(PhCN)2Cl2 PPh3
Pd(PhCN)2Cl2 dppp
5
28
2
2
19
2
46
5
27
0
99:1
99:1
99:1
99:1
99:1
99:1
99:1
99:1
99:1
–
9
Pd(PhCN)2Cl2 tBu3·BF4 Na2CO3
10
11
12
13
14
15[d]
Pd(PhCN)2Cl2 BINAP
Pd(PhCN)2Cl2 PCy3
Pd(PhCN)2Cl2 PCy3
Pd(PhCN)2Cl2 PCy3
Pd(PhCN)2Cl2 PCy3
Pd(PhCN)2Cl2 PCy3
Na2CO3
NaHCO3
K2CO3
Na2HPO4
Et3N
NaHCO3
NaHCO3
NaHCO3
66
89
22
99:1
99:1
99:1
16[d,e] Pd(PhCN)2Cl2 PCy3
17[d,f]
Pd(PhCN)2Cl2 PCy3
The reaction proceeded with high stereoselectivity to
form predominantly the Z isomer of styrenes 3. The mix-
ture contained less than 7% of the minor E isomer. This
result is in agreement with that observed in the Heck reac-
tion in the conventional stereochemistry. The Z selectivity
[a] Reaction conditions: 1a (1 mmol), 2 (18 mmol), catalyst (3 mol-
%), ligand (6 mol-%), base (2 mmol), BPO (2 mmol), DMF (3 mL),
110 °C, 14 h. dppp = 1,3-bis(diphenylphosphino)propane, BINAP
= 2,2Ј-bis(diphenylphosphino)-1,1Ј-binaphthyl. [b] Determined by
19F NMR spectroscopy by integrating the signal of the product rel-
ative to that of ethyl p-fluoroacetophenone as an internal standard.
[c] Determined by 19F NMR spectroscopy. [d] 1,4-Dioxane (3 mL) stems from both the stability of the olefin (thermodynamic)
was used as the solvent. [e] Pd(PhCN)2Cl2 (5 mol-%), PCy3
and a lower energy barrier in the transition state (kinetic),
(10 mol-%). [f] Compound 2: 5 mmol.
both of which lead to the Z isomer.[16] The trifluoromethyl
and isopropyl groups are comparable in size[17] in coupling
Control experiments revealed that the metal and ligand products 3, and the Z selectivity of the reaction is governed
were both indispensable for the reaction (Table 1, entries 2 by the stability of the alkene products in which the larger
and 3). The influence of the palladium catalyst was then trifluoromethyl group and the aryl group are in the trans
examined; Pd(PhCN)2Cl2 was found to be the best precata- orientation. The configuration of the isomers was deter-
lyst for the reaction (Table 1, entries 4 and 5). Next, a vari- mined by comparison of the fluorine and the vinylic proton
1
ety of ligands with varied electronic and steric properties in the H NMR spectra of fluoroalkenes 3. Nenajdenko[14]
were explored, and tricyclohexylphosphine gave the best reported that the JF,H vinylic hydrogen coupling constants
Eur. J. Org. Chem. 2015, 4340–4343
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4341

Z.-T. Liu, J. Lu et al.
SHORT COMMUNICATION
Table 2. Conversion of arylboronic acids into (Z)-β-fluoro-β-(tri- range from 28.0 to 36.3 Hz for Z isomers and from 18.2 to
fluoromethyl)styrenes through the Pd-catalyzed oxidative Heck re-
21.6 Hz for E isomers (Scheme 2).
action.[a]
Scheme 2. Assignment of configuration of isomeric alkenes 3.
Conclusions
In summary, we developed a new strategy for the facile
synthesis of (Z)-β-fluoro-β-(trifluoromethyl)styrene deriva-
tives through the palladium-catalyzed oxidative Heck reac-
tion of commercially available 2,3,3,3-tetrafluoroprop-1-ene
as a fluorine source. The wide scope and particularly the
tolerance to a large number of important arylboronic acids
make this strategy remarkably practical for the streamlined
synthesis of functional styrenes.
Experimental Section
General Procedure: The reaction was performed in an autoclave
containing a 10 mL Teflon reaction tube. The catalyst (0.05 mmol),
ligand (0.10 mmol), and a magnetic stir bar were placed in the tube,
which was then capped with a stopper. Then, p-anisylboronic acid
(1 mmol), base (2 mmol), oxidant (2 mmol), and the solvent (3 mL)
were added to the tube. The autoclave was cooled down to –100 °C
by using liquid nitrogen, and then a fixed amount of 2,3,3,3-tetra-
fluoropropylene was added. Finally, the autoclave was heated in an
oil bath at 115 °C for 6 h. Upon completion of the reaction, the
autoclave was cooled down to room temperature and vented care-
fully to discharge the excess amount of 2,3,3,3-tetrafluoropropyl-
ene. Water (60 mL) and p-fluoroacetophenone (80 mg) were added,
and then the product was extracted with CH2Cl2 (3ϫ 15 mL). The
organic layer was washed with brine, dried with Na2SO4, and con-
centrated under atmospheric pressure. The crude products were de-
termined by 19F NMR spectroscopy by using p-fluoroaceto-
phenone as an internal standard.
CAUTION: Because of the high volatility of the products, the reac-
tion must be performed carefully.
Acknowledgments
The authors gratefully acknowledge financial support from the
National Natural Science Foundation of China (NSFC) (grant
number 21327011), the Program for Changjiang Scholars and In-
novative Research Team in University (IRT_14R33), and the Post
Doctoral Research Project of Shaanxi Province, and also thank
Professor Chao Wang (SNNU) for helpful discussions.
[a] Reaction conditions: Arylboronic acid (1.0 mmol), 2 (18 mmol),
Pd(PhCN)2Cl2 (5 mol-%), PCy3 (10 mol-%), NaHCO3 (2 mmol),
BPO (2 mmol), 1,4-dioxane (3.0 mL), 110 °C, 14 h. [b] Determined
by analysis of the product by 19F NMR spectroscopy with p-fluoro-
acetophenone as an internal standard. The values in square brack-
ets are the yields of the isolated products. [c] Determined by
19F NMR spectroscopy.
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Received: May 11, 2015
Published Online: June 5, 2015
Eur. J. Org. Chem. 2015, 4340–4343
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