Palladium catalyzed mono and difunctionalization of hexafluorobut-2-yne

Article abstract of DOI:10.1016/j.tetlet.2016.08.025

The Pd(0) catalyzed one-pot mono and difunctionalization of hexafluorobut-2-yne is investigated. Styrenes and stilbenes can be obtained in high stereoselectivity by carbopalladation of phenylboronic acids and iodide benzenes. The reactions afford a facile access to a broad scope with good functional compatibility.

Full text of DOI:10.1016/j.tetlet.2016.08.025

Accepted Manuscript
Palladium catalyzed mono and difunctionalization of hexafluorobut-2-yne
Bo Zhao, Yang Li, Dong-Huai Tu, Wei Zhang, Zhao-Tie Liu, Jian Lu
PII:
S0040-4039(16)31011-5
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.08.025
TETL 47996
Reference:
Tetrahedron Letters
To appear in:
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Revised Date:
Accepted Date:
29 June 2016
4 August 2016
8 August 2016
Please cite this article as: Zhao, B., Li, Y., Tu, D-H., Zhang, W., Liu, Z-T., Lu, J., Palladium catalyzed mono and
difunctionalization of hexafluorobut-2-yne, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.
2016.08.025
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Tetrahedron Letters
Palladium catalyzed mono and difunctionalization of hexafluorobut-2-yne
Bo Zhaoa , Yang Lia , Dong-Huai Tua , Wei Zhanga , Zhao-Tie Liub, and Jian Lua, 
a State Key Laboratory of Fluorine & Nitrogen Chemicals, Xi’an Modern Chemistry Research Institute, Xi’an, 710065, China.
b Key Laboratory of Applied Surface and Colloid Chemistry (Ministry of Education), School of Chemistry and Chemical Engineering, Shaanxi Normal
University, Xi’an, 710119, China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The Pd (0) catalyzed one-pot mono and difunctionalization of hexafluorobut-2-yne is
investigated. Styrenes and stilbenes can be obtained in high stereoselectivity by carbopalladation
of phenylboronic acids and iodide benzenes. The reactions afford a facile access to a broad
scope with good functional compatibility.
Available online
2016 Elsevier Ltd. All rights reserved.
Keywords:
Palladium catalyzed
Carbometallation
Hexafluorobut-2-yne
Boronic acid
Synthetic method
1. Introduction
2. Results and discussion
Trifluoromethylated alkenes have been widely used in light-
emitting diodes (OLEDs) and anticancer drugs.1,2 The
incorporation of trifluoromethylated groups into olefins has
attracted increasing attention because of the significant
improvements in chemistry applications. Transition metal
catalyzed carbometalation was an effective approach to installing
the trifluoromethyl subunits, which could tolerate a wide variety
of important organic functional groups,3,4 and further
multicomponent coupling across internal alkynes are easily
transformed into tetrasubstitued alkenes.5,6
Initially, the addition of (4-methoxyphenyl)boronic acid (2a)
to 1,1,1,4,4,4-hexafluorobut-2-yne (1) was chosen as model
reaction. In the absence of palladium catalyst, no desired product
(3a) was observed (Table 1, entry 1). Then the influence of
catalyst was examined, tetrakis(triphenylphosphine) palladium
[Pd(PPh3)4] was found to be the best catalyst for the reaction,
other palladium catalysts such as palladium dichloride (PdCl2),
palladium acetate
Table 1 Optimization of the carbometalation additiona
The controllable synthesis of α,β-trifluoromethylstilbenes
under mild reaction conditions was particularly attractive,7 and
carbometalation of fluoroalkyne for introduction of
trifluoromethylated groups into olefins would be advantageous.
Burton8 and co-workers found the reaction of arylcopper reagents
addition to hexafluorobut-2-yne. Konno9 reported that
fluoroalkylated alkynes could undergo coupling reaction with
aryl iodides and arylboronic acids. In our recent work,
hexafluorobutyne was obtained from chlorohexafluorobutene
through dehydrochlorination,10 which enable the construction of
α,β-trifluoromethylated styrenes and stilbenes respectively.11
entry
1
2
3
4
5
6
7
8
[Pd]
-
PdCl2
solvent
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
DMF
THF
DCM
DCM
1,4-dioxane
yieldb (%)
0
15
40
25
84
51
15
79
94 (91)
89
Pd(OAc)2
Pd(PPh3)2Cl2
Pd(PPh3)4
Pd2(dba)3
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
9
10c
11c
Herein, we present
a palladium (0) catalyzed one-pot
7
carbometalation reaction of hexafluorobutyne for the synthesis of
hexafluoride styrene derivatives with good functional
compatibility, and further coupling reaction involving aryl
halides leading to the corresponding tetrasubstituted alkenes
stereoselectively.
a Reaction conditions: 1 (3 mmol), 2a (1 mmol), catalyst (5 mol%), solvent (2
mL), room temperature, 16 h.
b yields determined by 1H and 19F NMR, 4’-fluoroacetophenone as internal
standard.
———
 Corresponding author. a Tel.: +0-298-829-1367; e-mail: lujian204@263.net.
b Tel.: +0-298-153-0802; e-mail: ztliu@snnu.edu.cn.

2
Tetrahedron Letters
c catalyst (1 mol%).
After various bases were introduced in the transformation (Table
[Pd(OAc)2],
[Pd(PPh3)2Cl2],
Palladium
or
bis(triphenylphosphine)dichloride
3, entries 6-12), K2CO3 was found to be the most efficient,
tris(dibenzylideneacetone)dipalladium
increasing the yield of 5a to 51%.
[Pd2(dba)3] was inferior (Table 1, entries 2-6). Since the solvent
has a significant influence on the solubility of fluoroalkyne,
several solvents including N,N-dimethylformamide (DMF),
tetrahydrofuran (THF) and dichloromethane (DCM) were
screened with the latter providing the best yield (Table 1, entries
7-9). DCM was found to be quite successful even the catalyst
loadings reducing to 1 mol% (Table 1, entry 10), surprisingly, the
yield of desired alkene in 1,4-dioxane was dramatically
decreased from 84% to only 7% (Table 1, entry 11).
The three-component coupling process was further explored,
and compound 5 was obtained as the major product with high Z-
selectivities. An elevated temperature was used which
simultaneously increased the side reaction, as
a result,
tetrasubstituent was contaminated by biaryl and other byproducts.
For electron-rich reactants (Table 4, 5b), adducts obtained in
moderated yield, nitro group provided target compound in an
obviously dropping yield (Table 4, 5c).
Table 3 Three component coupling reactiona
Table 2 Carbopalladation of various boronic acidsa
entry
1
2
3
4
[Pd]
base
K2CO3
K2CO3
K2CO3
K2CO3
yieldb (%)
28
trace
18
Pd(PPh3)2Cl2
Pd(OAc)2
Pd(PhCN)2Cl2
Pd2(dba)3
22
5
6
7
8
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
K2CO3
Na2CO3
Cs2CO3
KHCO3
51 (44)
27
35
38
12
45
34
20
9
KH2PO4
K2HPO4•3H2O
K3PO4•7H2O
NaOAc
10
11
12
a
Reaction conditions: 1 (3 mmol), 2 (1 mmol), 3a (1 mmol), catalyst (5
mol%), DCM (2 mL), 100 oC, 16 h.
b
yields determined by 1H and 19F NMR, 4’-fluoroacetophenone as internal
standard.
Table 4 Coupling reaction of hexafluorobutynea
a Reaction conditions: 1 (3 mmol), 2 (1 mmol), Pd(PPh3)4 (5 mol%), DCM (2
mL), room temperature, 16 h, yields determined by 1H and 19F NMR, 4’-
fluoroacetophenone as internal standard.
b KHCO3 (3 mmol).
This strategy was applicable to a variety of phenylboronic
acids, giving the trisubstituted products with various functional
groups as a single stereoisomer. The results are summarized in
Table 2. Generally, substrates bearing electron donating or
electron withdrawing groups were suitable for this reaction,
leading to the desired α,β-trifluoromethylstyrenes in moderate to
good yields in cis fashion. Substrates with electron-rich group
like methoxy (Table 2, 3a), methyl (Table 2, 3b), butyl (Table 2,
3c and 3d), vinyl (Table 2, 3e), phenyl (Table 2, 3f) or benzyl
(Table 2, 3g) on the para-position of the aryl ring could
participate in this transformation smoothly. The heteroaryl
boronic acids (Table 2, 3h and 3i) were also well tolerated under
the optimized conditions. Para-, meta- or ortho-halides
substituents (Table 2, 3j-3n) did not hamper the reactivity, which
might be useful for further manipulation. Aryl boronic acids
bearing electron poor moieties such as carbonyl (Table 2, 3o and
3p), nitro (Table 2, 3r and 3s) or ester (Table 2, 3t)
functionalities were compatible with the reaction. To our delight,
cyano substituent remained intact, albeit employing a weaker
base was better for the formation of 3q.
a
Reaction conditions: 1 (3 mmol), 2 (1 mmol), 4 (1 mmol), Pd(PPh3)4 (5
mol%), K2CO3 (3 mmol), DCM (2 mL), 100 °C, 16 h, yields determined by
1H and19F NMR, 4’-fluoroacetophenone as internal standard.
3. Conclusions
In summary, an efficient addition of boronic acids with
functional groups to hexafluorobut-2-yne over a palladium
catalyst was developed, featuring a syn addition process. The
reactions could be carried out under mild conditions, allowing for
the synthesis of a variety of trifluoromethylated containing
alkenes. Further optimization for difunctional applicability is
underway in our laboratory.
Acknowledgments
In order to further demonstrate the utility of this protocol, a
palladium catalyzed three-component coupling reaction was
examined. The procedure was an effective tool for producing
stilbenes,12 investigation commenced with less hindered boronic
acid and iodide benzene (4a). Palladium sources were revaluated
(Table 3, entries 1-5), [Pd(PPh3)4] remained the best catalyst.
The authors gratefully acknowledge the financial support of
the National Natural Science Foundation of China (21403163,
21503610, 21327011), Natural Science Basic Research Plan in
Shaanxi Province of China (2014JQ2062).

Supplementary data
Text files giving additional experimental and characterization
1
data. Copies of the H, 13C and 19F NMR spectra of the products
produced in this study. Supplementary data associated with this
article can be found in the online version, at http://dx.doi.org/xxx.
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4
Tetrahedron Letters
Highlights

One-pot mono and difunctionalization
of hexafluorobut-2-yne is investigated
respectively.

Trisubstituted and tetrasubstituted α,β-
trifluoromethylstilbenzenes can be
obtained both in high Z-stereoselectivity.
The reaction featuring simple
manipulation.
The reaction could be carried out under
mild conditions.
The reaction affords a facile access for
a broad scope with good functional
compatibility.


