Synthesis of (E)-prop-1-ene-1,3-diyldibenzene derivatives via direct decarboxylative coupling of α,β-unsaturated carboxylic acids with benzyl boronic acid pinacol ester

Article abstract of DOI:10.1016/j.tetlet.2017.04.084

The first copper-catalyzed cross-coupling reaction between benzyl boronic acid pinacol ester and α,β-unsaturated carboxylic acids was described. The ready availability of the starting materials and excellent E selectivity make this protocol a safe and operationally convenient strategy for the efficient synthesis of (E)-prop-1-ene-1,3-diyldibenzene derivatives.

Full text of DOI:10.1016/j.tetlet.2017.04.084

Tetrahedron Letters xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of (E)-prop-1-ene-1,3-diyldibenzene derivatives via direct
decarboxylative coupling of
a,b-unsaturated carboxylic acids with
benzyl boronic acid pinacol ester
a,
Mingxiang Zhu a, Zhenjiang Qiu a, Yun Zhang a, Hongli Du a, Jingya Li b,c, Dapeng Zou a,b, , Yangjie Wu
,
⇑
⇑
Yusheng Wu b,d,
⇑
a The College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450052, PR China
b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China
c Tetranov Biopharm, LLC., No. 75 Daxue Road, Zhengzhou 450052, PR China
d Tetranov International, Inc., 100 Jersey Avenue, Suite A340, New Brunswick, NJ 08901, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The first copper-catalyzed cross-coupling reaction between benzyl boronic acid pinacol ester and
a
,b-
Received 15 March 2017
Revised 15 April 2017
Accepted 24 April 2017
Available online xxxx
unsaturated carboxylic acids was described. The ready availability of the starting materials and excellent
E selectivity make this protocol a safe and operationally convenient strategy for the efficient synthesis of
(E)-prop-1-ene-1,3-diyldibenzene derivatives.
Ó 2017 Published by Elsevier Ltd.
Keywords:
Decarboxylative cross-coupling
Cinnamic acid derivatives
Benzyl boronic acid pinacol ester
Introduction
coupling reaction between benzyl boronic acid pinacol ester with
amines to get the corresponding secondary and tertiary amines.7
Allylic derivatives are one of the most widely available building
blocks for modern organic synthesis and drug discovery research.1
Active allylic substrates bearing functional groups are commonly
used in allylic substitution reactions and evolved as powerful tools
for organic synthesis.2 Various synthetic methods were developed
for the synthesis of allylic compounds. In general, allylic deriva-
tives have been obtained by the following methods: (a) allylic sub-
stitution reactions of allylic ethers with Grignard reagents.3 (b)
Allyl-aryl coupling reaction of allylic carbonates with arylboronic
acids.4 (c) Cross-dehydrogenative-coupling reaction of toluol with
cinnamylic acids.5 Although these well-developed methods usually
give the target products in moderate to good yields, the discovery
of new methods or new catalytic system for the synthesis of these
compounds is still a demand. Aryl and alkyl boronic acids are
amongst the most widely available building blocks for modern
organic synthesis. Among them, benzyl boronic acid pinacol esters
are regarded as a kind of important organic boron reagents.6 In
2013, Sueki and Kuninobu reported the first Cu-catalyzed cross-
Suzuki and coworkers reported the Pd-catalyzed cross-coupling
reaction between benzyl- and cinnamyl boronic acid pinacol esters
with methyl iodide at the same year.8 However, benzyl boronic
acid pinacol esters in these reactions are considered to be more
challenging due to its lack of stability under the reaction
conditions.7
Recently, the decarboxylative cross-coupling reaction has
attracted much more attentions and it opens a new avenue for
the formation of carbon-carbon and carbon-heteroatom bonds.9
Carboxylic acids are always used as alternatives to halides and
organometal reagents in decarboxylative synthetic strategies.
Advanced progresses in decarboxylative bond formation (e.g. C–
C, C–N) have been reported by the groups of Goossen,10 Fu11 and
others.12 As to the decarboxylative cross-coupling reaction of cin-
namic acids and organoboronic acids, only limited examples were
reported.13,14 In 2010, Miura and co-workers reported the Pd-cat-
alyzed decarboxylative coupling reaction between cinnamic acids
and arylboronic acids in good to excellent yields.14 Herein, we
report the first copper-catalyzed cross-coupling reaction between
benzyl boronic acid pinacol ester and
acids to get the corresponding (E)-prop-1-ene-1,3-diyldibenzene
derivatives in moderate to good yields.
a,b-unsaturated carboxylic
⇑
Corresponding authors at: Collaborative Innovation Center of New Drug
Research and Safety Evaluation, Henan Province, PR China (D. Zou and Y. Wu).
E-mail addresses: zdp@zzu.edu.cn (D. Zou), wyj@zzu.edu.cn (Y. Wu), yusheng.
wu@tetranovglobal.com (Y. Wu).
http://dx.doi.org/10.1016/j.tetlet.2017.04.084
0040-4039/Ó 2017 Published by Elsevier Ltd.
Please cite this article in press as: Zhu M., et al. Tetrahedron Lett. (2017), http://dx.doi.org/10.1016/j.tetlet.2017.04.084

2
M. Zhu et al. / Tetrahedron Letters xxx (2017) xxx–xxx
(Table 1, entries 10, 17 and 18) and temperature (Table 1, entries
Results and discussion
19–22) were tested at last. The best yield was obtained under
120 °C for 12 h. The effect of gaseous environment (Table 1, entry
23) was also studied, and a better yield was get when the reaction
was performed under argon atmosphere. Various solvents (DMF,
DMA, DME, t-AmylOH, dioxane and toluene) (Table 1, entries 25–
30) were also investigated and DMSO was used as a better solvent
with 63% yield. This reaction could only be obtained in a moderate
yield due to the esterification of cinnamic acid as well as protona-
tion reaction and the side products including cinnamic esters and
styrene were observed by GC–MS. Finally, the optimum reaction
condition was obtained as follows: CuO (40 mol%) and Ag2CO3
(1.5 eq) as catalyst and oxidant, in DMSO (0.1 M) at 120 °C under
argon atmosphere for 12 h.
After the optimized reaction conditions in hand, various cin-
namic acids including electron-donating and electron-withdraw-
ing substituents were investigated. Halogenated substrates such
as F, Cl, Br were tested and fluorine atom substituted substrate
was found to give higher isolated yield (Table 2, entries 2–4). It
is worth noting that when Cl group located at meta-position, the
yield increased to some degree compared with those at ortho-
and papa-position. Next, substrates with electron donating groups
including methyl- (Table 2, entries 8–11) and methoxy- (Table 2,
entries 12–16) groups were tested. Similar to that halogenated
substrates, the desired meta-position products with electron
donating groups (methyl- and methoxy-) were obtained in higher
yields (Table 2, entries 9 and 12). Most of the cinnamic acids with
Initially, cinnamic acid and benzyl boronic acid pinacol ester
were chosen as model compounds to optimize the reaction condi-
tions. After screening various catalytic conditions, an available pro-
cess to get desired product by copper catalysis conditions was
found. A smooth reaction can be achieved by Cu(OAc)2 (50 mol%)
and Ag2CO3 (1.5 eq) as catalyst and oxidant in DMSO (0.1 M) at
120 °C under argon atmosphere for 12 h to afford a 38% yield of
the desired product. Various silver salts (AgOAc, AgF, AgNO3,
AgTFA, Ag2O and Ag2CO3) were screened (Table 1, entries 1–6)
and Ag2CO3 could give a better result with 38% yield. The copper
salt CuO (Table 1, entry 10) was indispensable to promote the
cross-coupling reaction. The yields of 3a were lower when using
other copper salts (Table 1, entries 7–16). Finally, the reaction time
Table 1
Decarboxylative coupling of cinnamic acid with benzyl boronic acid pinacol ester:
variation of reaction conditions.a
Entry
Catalyst
Oxidant
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OTf)2
CuCO3
CuSO4Á5H2O
CuO
Cu(OH)2
CuCl2
Cu2O
CuCl
CuI
Cu
CuO
CuO
CuO
CuO
CuO
CuO
CuO
AgOAc
AgF
AgNO3
AgTFA
Ag2CO3
Ag2O
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
20
19
Trace
Trace
38
37
26
36
41
63
31
34
40
31
25
32
40
45
Trace
35
45
63
40
45
33
Trace
Trace
Trace
Trace
Trace
Table 2
Decarboxylative cross-coupling reactions between several
a
,b-unsaturated carboxylic
acids and benzyl boronic acid pinacol ester.a
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
9
10
11
12
13
14
15
16
17c
18d
19e
20f
21g
22h
23i
24j
25
26
27
28
29
30
Entry
1
Substrate
Product
Yield (%)b
55
2
3
4
5
47
41
36
32
CuO
CuO
CuO
CuO
CuO
CuO
CuO
DMA
DME
t-AmylOH
Dioxane
Toluene
6
7
50
38
a
All reactions were performed with 0.2 mmol of cinnamic acid, 2 equiv of benzyl
boronic acid pinacol ester, 40 mol% of catalyst, 1.5 equiv of oxidant, 2 mL of solvent
at 120 °C for 12 h under Ar.
b
Yields were determined by GC–MS using diamyl phthalate as internal standard.
The reaction was performed for 4 h under Ar.
The reaction was performed for 8 h under Ar.
The reaction was performed at 60 °C under Ar.
The reaction was performed at 100 °C under Ar.
The reaction was performed at 110 °C under Ar.
The reaction was performed at 130 °C under Ar.
The reaction was performed under air.
8
38
58
54
c
d
e
9
f
g
h
10
i
j
The reaction was performed with 1.5 equiv of benzyl boronic acid pinacol ester.
Please cite this article in press as: Zhu M., et al. Tetrahedron Lett. (2017), http://dx.doi.org/10.1016/j.tetlet.2017.04.084

M. Zhu et al. / Tetrahedron Letters xxx (2017) xxx–xxx
3
the target product was obtained in moderate yield (Table 2, entry
23). However, the corresponding product was detected with only
trace amount by GC–MS when the cinnamic acid containing
nitro-substituent group was used. (Table 2, entry 24).
Table 2 (continued)
Entry
11
Substrate
Product
Yield (%)b
Trace
Conclusion
12
13
60
31
In conclusion, an efficient and mild synthetic procedure for the
synthesis of (E)-prop-1-ene-1,3-diyldibenzene derivatives starting
from
a,b-unsaturated carboxylic acids and benzyl boronic acid
14
15
46
22
pinacol ester was described. Our discovered method can easily
construct Csp2-Csp3 bond with two nucleophiles by traditional
metal catalyzed oxidative cross-coupling reactions. A wide range
of substrates could be used in this system and the desired (E)-
prop-1-ene-1,3-diyldibenzene derivatives will be very useful
building blocks in material science and drug discovery.
16
17
50
41
Acknowledgments
We are grateful to the National Natural Science Foundation of
China (21172200) and Research Program of Fundamental and
Advanced Technology of Henan Province (122300413203) for
financial support.
18
19
38
26
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