Copper-Mediated oxidative decarboxylative coupling of arylpropiolic acids with dialkyl h-phosphonates in water

Article abstract of DOI:10.1021/ol4037242

An efficient, mild, and generally applicable protocol for copper-mediated oxidative decarboxylative coupling of arylpropiolic acids with dialkyl H-phosphonates in water has been developed. Note that the reaction could proceed smoothly under air at relativ

Full text of DOI:10.1021/ol4037242

Letter
pubs.acs.org/OrgLett
Copper-Mediated Oxidative Decarboxylative Coupling of
Arylpropiolic Acids with Dialkyl H‑Phosphonates in Water
Xiang Li, Fan Yang,* Yangjie Wu, and Yusheng Wu*
The College of Chemistry and Molecular Engineering, Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key
Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052, People’s Republic of China
S
* Supporting Information
ABSTRACT: An efficient, mild, and generally applicable protocol for
copper-mediated oxidative decarboxylative coupling of arylpropiolic
acids with dialkyl H-phosphonates in water has been developed. Note
that the reaction could proceed smoothly under air at relatively low
temperature (60 °C), and the addition of isopropanol could successfully suppress the decomposition of dialkyl H-phosphonates
in water.
he phosphorus-containing compounds are of great
operate.10,11 Following this viewpoint, in 2011, Yang’s group
Timportance in organic synthesis, pharmaceuticals, and fulfilled the reaction of arylpropiolic acids and diphenylphos-
bioactive products.1−3 Among them, alkynylphosphonates have
phine oxide in NMP with the assistance of a Pd/Cu cocatalyst
system (Scheme 1b).12 However, this reaction did not work
attracted intense attention, because they could provide valuable
well for the dialkyl H-phosphonate, affording the product in a
yield of 42%.
scaffolds for the synthesis of other sophisticated phosphorus-
containing heterocycles through conjugate-addition or cyclo-
addition reactions.4 However, the traditional routes to
alkynylphosphonates such as the Michaelis−Arbuzov reaction
and the Michaelis−Becker reaction usually suffer from the prior
preparation of original materials and poor tolerance of
functional groups, thus restraining the applications of these
methodologies.3b,5
In recent years, the transition-metal-catalyzed Csp−P bond-
forming reaction has emerged as one of the most reliable and
robust tools for the synthesis of alkynylphosphonates.6 In 2009,
Han and Zhao reported the first successful copper-catalyzed
oxidative coupling of terminal alkynes with H-phosphonates in
DMSO, affording the corresponding alkynylphosphonates in
high yields (Scheme 1a).6a On the other hand, the
decarboxylative coupling reaction as a new synthetic strategy
has wide applications in the construction of C−C and C−
heteroatom bonds.7,8 Particularly, arylpropiolic acids are usually
solid-state without pungent smell and easy to prepare, store,
and transport.9 Therefore, taking arylpropiolic acids instead of
terminal alkynes would make the reaction safer and easier to
On the other hand, water as an ideal green solvent can
potentially provide benefits for chemical syntheses in terms of
resource economy, energy efficiency, and health and environ-
mental safety.13 As we know, dialkyl H-phosphonates tend to
decompose to phosphorous acid and isopropanol in water, and
therefore, the reaction involving dialkyl H-phosphonates in
water would be rich in challenges. Just recently, we have
realized the reaction of aryl halides with diisopropyl H-
phosphonate in neat water using isopropanol as the additive,
which successfully suppressed the decomposition of dialkyl H-
phosphonates.14 In this work, we attempt to develop a mild,
simple, and green protocol for the copper-mediated oxidative
decarboxylative coupling of arylpropiolic acids with dialkyl H-
phosphonates in water under air (Scheme 1c). In this reaction,
the effect of isopropanol as the additive on the decomposition
of dialkyl H-phosphonates in water would also be discussed.
Initially, we performed a reaction of phenylpropiolic acid
(1a) with diisopropyl H-phosphonate (2a) in water under air in
the presence of 2 equiv of Cu(OAc)2·H2O and 2 equiv of
K3PO4, and the desired product was obtained in 28% yield
(Table 1, entry 1). Subsequently, we checked some
commercially available ligands (e.g., TMEDA, Et3N, DABCO,
2,2′-bipyridine, and 1,10-phenanthroline), and when 1,10-
phenanthroline was used the yield of desired product could
be up to 71% (Table 1, entries 2−6). Then, the reaction
conditions were further optimized by the addition of different
additives (Table 1, entries 7−11). When the traditional
surfactant TBAB was added, the yield slightly increased to
75% yield (Table 1, entry 7). To our delight, the simple bulky
Scheme 1. Transition-Metal-Catalyzed Csp-P Bond Forming
Reaction
Received: December 23, 2013
Published: January 29, 2014
© 2014 American Chemical Society
992
dx.doi.org/10.1021/ol4037242 | Org. Lett. 2014, 16, 992−995

Organic Letters
Letter
a
Table 1. Optimization of the Reaction Conditions
Scheme 2. Decarboxylative Coupling of Propiolic Acids with
H-Phosphonates
ab
,
b
entry
copper salt
ligand
additive
yield (%)
1
2
3
4
5
6
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OTf)2
−
−
−
−
−
−
−
28
34
21
20
10
71
75
88
83
79
82
84
66
73
37
70
71
77
TMEDA
Et3N
DABCO
2,2′-Bipyridine
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
1,10-Phen
c
7
TBAB
iPrOH
tBuOH
nBuOH
tAmOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
iPrOH
8
9
10
11
d
12
e
13
f
14
g
15
16
17
18
CuSO4·5H2O
CuCl2
a
Reaction conditions: phenylpropiolic acid 1a (0.2 mmol), diisopropyl
H-phosphonate 2a (0.4 mmol), copper salt (2.0 equiv), ligand (2.5
equiv), K3PO4 (2.0 equiv), additive (3.0 equiv), and H2O (2.5 mL) at
b
c
60 °C under air for 24 h. Isolated yield. TBAB (1.0 equiv) was used.
d
e
f
g
At 80 °C. At 40 °C. 1 equiv of Cu(OAc)2·H2O was used. 20 mol %
of Cu(OAc)2·H2O was used.
a
Reaction conditions: arylpropiolic acid 1 (0.2 mmol), H-phosphonate
2 (0.4 mmol), Cu(OAc)2·H2O (2.0 equiv), 1,10-phenanthroline (2.5
alkyl alcohols (e.g., iPrOH, tBuOH, nBuOH and tAmOH) were
found to be particularly beneficial for this reaction (Table 1,
entries 8−11). Remarkably, PrOH as the additive could afford
i
equiv), K3PO4 (2.0 equiv), PrOH (3.0 equiv), and H2O (2.5 mL) at
60 °C under air for 24 h. Isolated yield.
b
i
the desired product in a yield of up to 88%, which may be
attributed to its suppressive role for the decomposition of the
diisopropyl H-phosphonate in water and phase transfer catalytic
property (Table 1, entry 8). Finally, some controlling
experiments were performed. For example, performing the
reaction at higher temperature of 80 °C or lower temperature
of 40 °C, changing the amount of Cu(OAc)2·H2O to 1 equiv or
even substoichiometric amount (20 mol %), did not afford the
products in higher yields (Table 1, entries 12−15). Other
copper sources such as Cu(OTf)2, CuSO4·5H2O, and CuCl2
were also checked, but they could only give slightly lower yields
of 70, 71, and 77%, respectively (Table 1, entries 16−18).
With optimized conditions in hand, we next explored the
scope of the substrates and the results are summarized in
Scheme 2. First, the reaction could well tolerate diverse dialkyl
H-phosphonates and afford the corresponding products in
moderate to good yields of 65−88% (Scheme 2, 3a−3f). The
scope of arylpropiolic acids bearing various functional groups
was then checked, and the electronic effect had an obvious
influence on this decarboxylative coupling (Scheme 2, 3g−3s).
For example, electron-rich arylpropiolic acids have a relatively
lower reactivity, only affording the corresponding products in
moderate yields ranging from 42 to 53%, accompanied by the
generation of diynes as the byproducts (Scheme 2, 3h−3j). It
was exceptional that 4-methylphenylpropiolic acid could
generate the desired product in a good yield of 73% (Scheme
2, 3g). On the contrary, both electron-poor and electron-
neutral arylpropiolic acids could well be coupled with
diisopropyl H-phosphonate (2a) affording the products in
moderate to good yields (Scheme 2, 3k−3s). Functional groups
(e.g., F, Cl, Br, CH3CO, NO2, and CF3) could well be tolerated
in this reaction (Scheme 2, 3m−3s), and particularly, the
arylpropiolic acid bearing two halogen atoms could be
converted to the desired product in a yield of 80% (Scheme
2, 3p). The heterocyclicpropiolic acid could also afford the
desired product in a yield of 40% (Scheme 2, 3t). In addition,
alkylpropiolic acid, 2-octynoic acid was also checked, but
unfortunately, only trace amount of the product was detected
by GC−mass analysis (Scheme 2, 3u).
To further extend the scope of this reaction, the alkynylation
of diphenylphosphine oxide was explored (Scheme 3). Under
base-free conditions, the reaction could afford the desired
product in a yield of 41%, presumably because of its insolubility
in water.
To reveal the advantage of this methodology, the reactions of
diisopropyl H-phosphonate (2a) with some other common
acetylene sources such as phenylacetylene (4a), 1-phenyl-2-
(trimethylsilyl)acetylene (4b), and 2-methyl-4-phenylbut-3-yn-
2-ol (4c) were carried out under the optimized conditions
Scheme 3. Decarboxylative Coupling of Propiolic Acid with
Diphenylphosphine Oxide
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Organic Letters
Letter
(Scheme 4). However, these reactions either gave the desired
product (3a) in lower yields (4a and 4b) or did not take place
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: yangf@zzu.edu.cn.
Scheme 4. Comparative Experiments of Different Acetylene
Sources
*E-mail: yusheng.wu@tetranovglobal.com.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (No. 21172200, 21102134) for financial support to this
research.
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phosphonates is outlined as Scheme 5. First, the coordination
■
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ASSOCIATED CONTENT
■
S
* Supporting Information
General experimental procedure and characterization data of
the products. This material is available free of charge via the
Internet at http://pubs.acs.org.
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