Silver-Mediated Selective Oxidative Cross-Coupling between C-H/P-H: A Strategy to Construct Alkynyl(diaryl)phosphine Oxide

Article abstract of DOI:10.1021/ol503341t

(Formula Presented) A direct oxidative cross-coupling between terminal alkynes and secondary phosphine oxides was developed. This approach provides an efficient way to construct alkynyl di(phenyl) phosphine oxides from basic materials, and in this process

Full text of DOI:10.1021/ol503341t

Letter
pubs.acs.org/OrgLett
Silver-Mediated Selective Oxidative Cross-Coupling between C−H/
P−H: A Strategy to Construct Alkynyl(diaryl)phosphine Oxide
Tao Wang,† Songtao Chen,† Ailong Shao,† Meng Gao,*,† Yangfei Huang,† and Aiwen Lei*,†,‡
†National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, Jiangxi P. R. China
‡College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, Hubei P. R. China
S
* Supporting Information
ABSTRACT: A direct oxidative cross-coupling between terminal
alkynes and secondary phosphine oxides was developed. This approach
provides an efficient way to construct alkynyl di(phenyl) phosphine
oxides from basic materials, and in this process, the silver salts act as a key promoter.
n terms of avoiding prefunctionalization of substrates, the
direct oxidative coupling between two different C−H or
Wu,6e respectively, realized the synthesis of alkynyl(diaryl)-
phosphine oxides, but alkyne acid was employed instead of
alkyne to react with Ph2P(O)H. Recently, Zhao and Zhu
further reported a Cu-catalyzed phosphorylation of terminal
alkynes to achieve the synthesis of alkynyl(diaryl)phosphine
oxides by adding the diphenylphosphine oxide to the reaction
mixture dropwise, in which only one example was presented .6g
Based on our continued interest in the development of terminal
alkyne chemistry with silver salts, we envisioned that the direct
oxidative coupling of terminal alkynes with Ph2P(O)H might
be generally achieved. This protocol would address the previous
limitations and furnish a diverse collection of valuable
alkynyl(diaryl)phosphine oxides from basic chemical materials.
Our initial efforts focused on the reaction of 1-ethynyl-4-
methylbenzene 1a and diphenylphosphinoxide 2a by using
different silver(I) salts. To our delight, we found that the
corresponding alkynyl(diaryl)phosphine oxides product was
indeed obtained, albeit in low yields, when AgI, AgNO3, Ag2O,
and Ag2CO3 were applied as the promoters (Table 1, entries
1−4). This interesting transformation encouraged us to further
examine the feasibility of this direct oxidative cross-coupling.
After many efforts, the employment of Ag2CO3 (2.0 equiv)
in DMSO at 120 °C was found to be the best reaction
conditions for this direct C−H/P−H oxidative cross-coupling
(Table 1, entry 8). Importantly, the reaction displayed high
selectivity. Even though the two substrates were added in one
pot, no terminal alkynes homocoupling and other byproducts
were observed. Ag2O could also provide the desired product in
17% yield, while AgI and AgNO3 were totally ineffective (Table
1, entries 1−3). A lower amount of Ag2CO3 would afford lower
yields (Table 1, entries 4 and 5). When the reaction
temperature was decreased to 80 °C, the desired product
could be obtained in only 47% yield (Table 1, entry 7).
However, increasing the temperature did not improve the yield
(Table 1, entries 9). The reaction could also proceed in other
solvents, such as polar solvents DMF and DCE, albeit in lower
yields (Table 1, entries 10 and 11). When toluene was used,
I
heteroatom−H bonds is superior to the classical transition-
metal-catalyzed coupling reactions, and it represents an ideal
organic synthesis in modern chemical society.1 In this emerging
field, the highly efficient and selective oxidative cross-coupling
reactions involving terminal alkynes are still challenging, since
inevitable homocoupling of terminal alkynes negatively affects
the reactions.2 Very recently, the combination of terminal
alkynes and silver salts has shown potential in the construction
of interesting heterocycles in a selective manner, in which
alkyne homocoupling product is successfully avoided,3 thereby
suggesting that the combination of terminal alkynes and silver
salts does not tend to occur homocoupling of terminal alkynes.
Undoubtedly, this method offers more possibilities for
exploring oxidative cross-couplings involving terminal alkynes
as the nucleophiles. Herein, we report the first silver-mediated
oxidative cross-coupling between terminal alkynes and
secondary phosphine oxide to construct alkynyl di(phenyl)
phosphine oxides (Scheme 1).
Scheme 1. Silver-Mediated C−H/P−H Direct Oxidative
Cross-Coupling
Alkynyl(diaryl)phosphine oxides are important precursors to
synthesize various (P^O) or (P^N) bidentate ligands.4 The
traditional routes to alkynylphosphonates, such as the
Michaelis−Arbuzov reaction and the Michaelis−Becker reac-
tion, usually suffer from prefunctionalization of the starting
materials and poor tolerance of functional groups.5 Thus, it is
still imperative to develop novel methods to improve the
synthetical efficiency.6 In 2009, Han and Zhao6a reported a
copper-catalyzed oxidative coupling of alkynes with (iPrO)2P-
(O)H, which significantly simplified the process. However,
secondary phosphine oxide Ph2P(O)H was not tolerated to
afford the corresponding product under their reaction
conditions. Soon after, the groups of Yang and Liang6d and
Received: November 18, 2014
© XXXX American Chemical Society
A
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Table 1. Impact of Reaction Parameters on the Direct
Oxidative Cross-Coupling
Scheme 2. Reactions of Alkynes 1 and Secondary Phosphine
Oxides 2.
a
a
b
entry
[Ag]
temp (°C)
solvent
yield (%)
1
1.0 equiv of AgI
100
100
100
100
100
100
80
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
trace
trace
17
2
1.0 equiv of AgNO3
1.0 equiv of Ag2O
3
4
1.0 equiv of Ag2CO3
0.5 equiv of Ag2CO3
2.0 equiv of Ag2CO3
2.0 equiv of Ag2CO3
2.0 equiv of Ag2CO3
2.0 equiv of Ag2CO3
2.0 equiv of Ag2CO3
2.0 equiv of Ag2CO3
2.0 equiv of Ag2CO3
2.0 equiv of Ag2CO3
40
5
16
6
60
7
47
8
120
140
120
120
120
120
70
9
68
10
11
12
51
DCE
43
toluene
DMSO
trace
37
c
13
a
The reaction was carried out with 1a (0.3 mmol), 2a (0.2 mmol), 15
b
c
h, 3 mL of solvent, N2. Isolated yield. The reaction was carried out
under air.
only a trace amount product was obtained (Table 1, entry 12).
The reaction could also proceed under air to generate the
desired product, albeit in lower yield (Table 1, entry 13).
With the optimized conditions in hand, varied terminal
alkynes 1 were found to be suitable reaction partners with
diphenylphosphine oxide 2a to provide the corresponding
alkynyl(diaryl)phosphine oxides (Scheme 2). Both electron-
withdrawing and electron-donating substituted groups or
halogen groups at the aromatic ring of arylalkynes were well
tolerated in the reactions, such as Me, OMe, Cl, Br, F, COEt,
phenyl, n-pentyl, and n-butyl (Scheme 2, 3a−i,m−o). Mean-
while, arylalkynes with substituents at the ortho, meta, or para
position of the aromatic ring could react smoothly to afford the
desired products in moderate to good yields. Terminal alkynes
containing thiophene and pyridine moieties could also be
employed to give the corresponding product in 54% and 52%
yields, respectively (Scheme 2, 3j and 3k). Moreover, alkyl
terminal alkynes were also found to be suitable reaction
partners with diphenylphosphine oxide 2a in the reaction.
Aliphatic terminal alkynes, including those with cyclopropyl
and tert-butyl, could also react with 2a to afford the
corresponding products in moderate yields (Scheme 2, 3t,u).
In addition, ethyl propiolate was also suitable for this reaction
(Scheme 2, 3v).
a
Reactions of alkynes 1 and secondary phosphine oxides 2. Reaction
conditions: The reactions were carried out with 1 (0.3 mmol), 2 (0.2
mmol), Ag2CO3 (0.4 mmol), N2, DMSO (3 mL), 120 °C, 15 h,
isolated yield.
treatment with nitric acid and Na2CO3 (for the details of the Ag
recovery experiment, see the Supporting Information). The
regenerated Ag2CO3 could still promote this oxidative cross-
coupling in comparable yield without loss of activity (Scheme
3).
Varied secondary phosphine oxides are also tested to access
the corresponding product. Various substituted groups at the
aromatic ring of phosphine oxides could be introduced into the
desired product, such as Cl, F, and Me (Scheme 2, 3p−r). Ethyl
phenylphosphinate could also react smoothly to afford the
desired product in moderate yield (Scheme 2, 3s). Unfortu-
nately, under the current reaction conditions, (EtO)2P(O)H
could not afford the oxidative cross-coupling product (Scheme
2, 3w).
To gain preliminary mechanistic information about this
transformation, the prepared silver acetylide was reacted with
2a under the standard conditions. As shown in Scheme 4a, in
the presence of additional Ag2CO3, silver phenylacetylide could
indeed react with 2a and afford the desired product in 60%
Scheme 3. Recovery Experiments of Ag Salts
The silver salts could be reused. An undisputable issue is the
application of 2 equiv of Ag2CO3 in this reaction. It is well-
known that Ag2CO3 is one of the most cost-effective silver
sources; however, the cost and waste are still worth attempting
to save.3b Actually, excess Ag2CO3 and all silver species after the
reaction could be recycled conveniently by filtration and
B
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Letter
single-electron oxidation. However, details of the mechanism
are not clear at present. Our current efforts are focused on
probing the mechanism of this oxidative transformation.
In summary, we have developed a novel silver-mediated
highly selective oxidative C−H/P−H direct cross-coupling,
which provided an efficient entry to the alkynyl(diaryl)-
phosphine oxides in one step. From a synthetic point of
view, this protocol represents an efficient way to alkynyl-
(diaryl)phosphine oxides from basic starting materials. The
combination of terminal alkynes and silver salts acts as a “dream
ticket” for high selectivity in this oxidative C−H/P−H cross-
coupling reaction.
Scheme 4. (a) Reaction of 2a and Silver Phenylacetylide. (b)
Reaction of 1a and (Ph)2P(O)Ag. (c) Reaction of (Ph)2P(O)
Ag and Silver Phenylacetylide
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedure, characterization data, and copies of
1H, 13C, and 19P NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: drmenggao@163.com.
*E-mail: aiwenlei@whu.edu.cn.
Notes
The authors declare no competing financial interest.
Caution! The reaction apparatus should be placed behind blast
shields to avoid safety issues.
yield. Without additional Ag2CO3, only 17% yield was obtained.
The prepared (Ph)2P(O)Ag (for the preparation methods, see
the Supporting Information) was also reacted with phenyl-
acetylene. As shown in Scheme 4b, in the presence of additional
Ag2CO3, the desired product could be obtained in 37% yield.
Without additional Ag2CO3, only a trace amount of product
was obtained. The stoichiometric reaction between (Ph)2P(O)
Ag and silver phenylacetylide was also performed, and the
corresponding product could be obtained in 30% yield
(Scheme 4c); in the presence of additional Ag2CO3, 71%
yield was obtained.
ACKNOWLEDGMENTS
■
This work was financially supported by the National Natural
Science Foundation of China (Nos. 21262018 and 20862007)
and the Natural Science Foundation of Jiangxi Province
(2010GZH0070).
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