Palladium-catalyzed dehydrogenative coupling of terminal alkynes with secondary phosphine oxides

Article abstract of DOI:10.1039/c4cc09567g

The dehydrogenative coupling of terminal alkynes with secondary phosphine oxides is developed. In the presence of a silver additive, palladium acetate could efficiently catalyze the dehydrocoupling of secondary phosphine oxides with a variety of terminal alkynes to produce the corresponding alkynylphosphine oxides in high yields. A reaction mechanism is proposed. This journal is

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ARTICLE TYPE
Palladium-Catalyzed Dehydrogenative Coupling of Terminal Alkynes
with Secondary Phosphine Oxides
Jia Yang,a Tieqiao Chen,*a Yongbo Zhou,a Shuangfeng Yina and Li-Biao Han*a, b
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
40
We accidently found this reaction during our studies on metalꢀ
catalyzed P(O)H additions to alkynes.7 We noted that a trace
amount of 2 could be occasionally detected by GCꢀMass from the
reaction mixture when Pd(OAc)2 was used as a catalyst precursor.
A careful pursuit of this phenomena leads to the disclosure of the
The dehydrogenative coupling of terminal alkynes with
secondary phosphine oxides is developed. In the presence of a
silver additive, palladium acetate could efficiently catalyze the
dehydrocoupling of secondary phosphine oxides with a
10 variety of terminal alkynes to produce the corresponding
alkynylphosphine oxides in high yields. A reaction mechanism
is proposed.
45 present new reaction (eq 2). Thus, by carrying out extensive
screening experiments on the reaction conditions, we realized that
phenylacetylene and diphenylphosphine oxide 1a could be
coupled efficiently in the presence of a catalytic amount of
palladium acetate with a proper additive (Table 1).
The transition metalꢀcatalyzed dehydrogenative coupling reaction
is a clean way for the construction of new chemical bonds (eq
15 1).1,2 By employing this method, two substrates can be coupled
50 Table 1 Palladiumꢀcatalyzed dehydrocoupling of diphenylphosphine
oxide 1a with phenylacetylenea
without
prefunctionalization.
The
preparation
of
organophosphorus compounds via this dehydrocoupling method
is recently attracting great attention.3
(1)
20
Having a chemically reactive carbonꢀcarbon triple bond,
alkynylphosphinyl compound are versatile reagents for the
preparation of highly functional phosphorus compounds through
conjugate addition reactions, metallacycle formation and unique
cycloadditions.4,5 Some of them are also biologically active.6
25 Traditionally, these compounds are prepared by a few methods
with the reaction using hazard chemical R2P(O)Cl with Li or Mg
acetylides being the most frequently employed, which suffers
from lack of functionality’s tolerance.5 Recently, an aerobic
oxidative coupling of terminal alkynes with Hꢀphosphonates
30 catalyzed by copper was reported.3n Very unfortunately,
however, this reaction is not applicable to secondary phosphine
oxides 1 to prepare the corresponding alkynylphosphine oxides 2,
because of the severe oxidations of 1 and alkynes under the
reaction conditions. Herein, we disclose an efficient palladiumꢀ
35 mediated dehydrogenative coupling of 1 with a variety of
terminal alkynes to selectively produce the valuable
alkynylphosphorus compounds 2 in high yields under mild
conditions (eq 2).
aReaction conditions: 1a (0.2 mmol), phenylacetylene (0.2
mmol), 5 mol% Pd catalyst, additive (0.4 mmol), solvent (1 mL).
bGC yield using dodecane as an internal standard
.
55
As shown in Table 1, the catalytic dehydrocoupling reaction of
diphenylphosphine oxide 1a with phenylacetylene in THF
catalyzed by 5 mol% Pd(OAc)2 took place quickly in the
(2)
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DOI: 10.1039/C4CC09567G
presence of AgBF4 at 40 oC to give the corresponding
phenylethynyldiphenylphosphine oxide 2a in 91% yield after 3 h 60 respectively (entries 22 and 23). Bulky dicyclohexylphosphine
the corresponding 2v and 2w in 80% and 75% yields,
(entry 1). The starting materials were completely consumed and a
oxide 1d reacted with phenylacetylene to give 2x in 59% yield
(entry 24). HꢀPhosphinate esters 1e and Hꢀphosphonates 1f also
served good substrates in this reaction to produce the
corresponding 2y and 2z in 91% and 85% yields, respectively
nearly quantitative yield of 2a was obtained when the reaction
o
5
was conducted at a slightly higher temperature (60 C) (entry 2).
Among the additives investigated, AgBF4 gave the highest yield
compared to other silver salts and copper salts (entries 3ꢀ9). A 65 (entries 25 and 26).
palladium catalyst is essential for this dehydrocoupling reaction.
In the absence of the palladium catalyst, 2a could not be detected
Table 2 Palladiumꢀcatalyzed dehydrocoupling of secondary phosphine
oxides 1 with terminal alkynes producing alkynylphosphine oxides 2a
10 at all (entry 11). In addition to palladium acetate, palladium
chloride (entry 12) also gave 17% yield of 2a. However,
Pd2(dba)3 hardly promoted the reaction (entry 13). In addition to
THF, the dehydrocoupling could also proceed efficiently in
methanol (entry 14). However, it hardly proceeded in DMF,
15 toluene and ether (entries 15ꢀ17). Another remarkable feature of
this reaction is that although the palladium catalyzed addition of
Ph2P(O)H to phenylacetylene forming the addition adducts could
be possible,7 no such adducts was detected under the present
reaction conditions.
cat. Pd(OAc)2, AgBF4
R
R1R2P(O)
R1R2P(O)H
R
60 oC, 1 mL THF
2
1
Entry
1
Alkyne
P(O)-H
Product Isolated Yield
Ph2P(O)H
2a
92%
Ph
1a
o-Me-C6H4
2
2b
86%
89%
87%
trace
n.d.
3
m-Me-C6H4
p-Me-C6H4
p-MeO-C6H4
p-H2N-C6H4
p-F-C6H4
2c
2d
2e
2f
4
5
20
This palladiumꢀcatalyzed dehydrocoupling is a rather general
method for the preparation of alkynylphosphine oxides 2. Thus,
as shown in Table 2, a variety of terminal alkynes, both aromatic
and aliphatic, can readily react with secondary phosphine oxides
1 to produce the corresponding alkynylphosphine oxides 2
6
7
2g
2h
2i
84%
89%
81%
85%
p-Cl-C6H4
8
p-Br-C6H4
p-F3C-C6H4
9
10
2j
25 selectively. Worth noting is that this dehydrocoupling features a
wide tolerance to a variety of functional groups. Thus fluoro
(entry 7), chloro (entry 8), trifluoromethyl (entry 10), ester (entry
15), and carboxyl group (entry 16), all are compatible under the
present catalytic conditions. Surprisingly, as exemplified by the
30 reaction of 4ꢀbromophenylacetylene, even an organyl bromide
that can couple with P(O)ꢀH in the presence of a palladium
catalyst,8 also can be used as the substrate, to give the
corresponding dehydrocoupling product 2i in 81% yield (entry 9).
More surprisingly, although Ph2P(O)H can nucleophilically add
35 to a carbonyl group,9 the dehydrocoupling product 2k could be
obtained in a high yield from 1ꢀ(4ꢀethynylphenyl)ethanone (entry
11), in which no such byꢀproduct via the addition of Ph2P(O)H to
the carbonyl group was detected. As shown in the table, an aryl
alkyne with a methoxy or an amino group showed low reactivity
p-Ac-C6H4
11
2k
84%
α-naphthyl
12
13
2l
60%
C6H4
2m
trace
n-C6H13
14
15
2n
2o
2p
95%
92%
MeO2C(H2C)8
HO2C(H2C)8
16
70%
17
90%
2q
18b
19b
2r
74%
56%
t-Bu
2s
40 in this reaction (entries
5 and 6). The reaction of 1ꢀ
91%
68%
80%
2t
20
21
ethynylnaphthalene with Ph2P(O)H gave 60% yield of the
corresponding dehydrocoupling product 2l (entry 12). However,
only trace of product was detected when 1,4ꢀdiethynylbenzene
was employed under similar reaction conditions (entry 13). The
45 reaction was also applicable to aliphatic alkynes. Thus, the
catalytic dehydrocoupling of Ph2P(O)H with 1ꢀoctyne took place
efficiently to afford 2n in 95% isolated yield (entry 14). Other
aliphatic alkynes also served as good substrates for this reaction
producing the corresponding alkynylphosphine oxides in high
50 yields (entries 14ꢀ20).
n-Bu2P(O)H
Ph
Ph
2u
1b
n-BuPhP(O)H
22
2v
1c
n-C6H13
23
24
2w
2x
75%
59%
Cy2P(O)H
Ph
1d
25c
Ph(EtO)P(O)H
91%
85%
Ph
Ph
2y
2z
1e
26c,d
(i-PrO)2P(O)H
1f
As to the secondary phosphine oxide, both aliphatic and
aromatic substrates could be used in this reaction. Thus, in
addition to Ph2P(O)H 1a, nꢀBu2P(O)H 1b also readily reacts with
aReaction conditions: 0.2 mmol 1, 0.2 mmol alkyne, 5 mol% Pd(OAc)2,
0.4 mmol AgBF4, 1 mL THF, 60 oC, 3ꢀ24 h. b100 oC, 18 h. c0.4 mmol
70 Et3N, 100 oC, 18 h. d 0.4 mmol alkyne was added.
phenylacetylene
to
produce
the
corresponding
55 (phenylethynyl)dibutylphosphine oxide 2u in 68% yield (entry
21). Butylphenylphosphine oxide nꢀBuPhP(O)H 1c is also as
reactive as other secondary phosphine oxides. Compound 1c
efficiently reacted with phenylacetylene and 1ꢀoctyne to produce
On the basis of the above experimental results, several control
experiments10 and the previous studies,11 we assume that this
2
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2001, 40, 4694; (h) L.ꢀB. Han and T. D. Tilley, J. Am. Chem. Soc.,
2006, 128, 13698; (i) R. Waterman, Organometallics, 2007, 26,
2492; (j) J. Fraser, L. J. Wilson, R. K. Blundell and C. J. Hayes,
Chem. Commun., 2013, 49, 8919; (k) G. Wang, Q.ꢀY. Yu, S.ꢀY.
Chen and X.ꢀQ. Yu, Tetrahedron Lett., 2013, 54, 6230; (l) Y. Zhou,
J. Yang, T. Chen, S.ꢀF. Yin, D. Han and L.ꢀB. Han, Bull. Chem.
Soc. Jpn., 2014, 87, 400; (m) Y. Zhou, S. Yin, Y. Gao, Y. Zhao, M.
Goto and L.ꢀB. Han, Angew. Chem. Int. Ed., 2010, 49, 6852.
Recent CꢀP bonding formation via dehydrocoupling: (a) D. P. Hari
and B. König, Org. Lett., 2011, 13, 3852; (b) O. Baslé and C.ꢀJ. Li,
Chem. Commun., 2009, 4124; (c) Y.ꢀM. Li, M. Sun, H.ꢀL. Wang,
Q.ꢀP. Tian and S.ꢀD. Yang, Angew. Chem. Int. Ed., 2013, 52, 3972;
(d) C.ꢀG. Feng, M. Ye, K.ꢀJ. Xiao, S. Li and J.ꢀQ. Yu, J. Am. Chem.
Soc., 2013, 135, 9322; (e) X. Mi, M. Huang, J. Zhang, C. Wang and
Y. Wu, Org. Lett., 2013, 15, 6266; (f) T. Kagayama, A. Nakano, S.
Sakaguchi and Y. Ishii, Org. Lett., 2006, 8, 407; (g) B. Yang, T.ꢀT.
Yang, X.ꢀA. Li, J.ꢀJ. Wang and S.ꢀD. Yang, Org. Lett., 2013, 15,
5024; (h) X.ꢀQ. Pan, J.ꢀP. Zou, G.ꢀL. Zhang and W. Zhang, Chem.
Commun., 2010, 46, 1721; (i) C. Hou, Y. Ren, R. Lang, X. Hu, C.
Xia and F. Li, Chem. Commun., 2012, 48, 5181; (j) C. Li, T. Yano,
N. Ishida and M. Murakami, Angew. Chem. Int. Ed., 2013, 52, 9801;
(k) X.ꢀJ. Mu, J.ꢀP. Zou, Q.ꢀF. Qian and W. Zhang, Org. Lett., 2006,
8, 5291; (l) C.ꢀB. Xiang, Y.ꢀJ. Bian, X.ꢀR. Mao and Z.ꢀZ. Huang, J.
Org. Chem., 2012, 77, 7706; (m) H. Wang, X. Li, F. Wu and B.
Wan, Synthesis, 2012, 44, 941; (n) Y. Gao, G. Wang, L. Chen, P.
Xu, Y. Zhao, Y. Zhou and L.ꢀB. Han, J. Am. Chem. Soc., 2009, 131,
7956. Very recently, Zhao et al have reported a Cuꢀassisted
dehydrocoupling of Ph2P(O)H with phenylacetylene by using a
delicate slowꢀaddition process: (o) L. Liu, Y. Wu, Z. Wang, J. Zhu
and Y. Zhao, J. Org. Chem., 2014, 79, 6816.
(a) A. Kondoh, H. Yorimitsu and K. Oshima, J. Am. Chem. Soc.,
2007, 129, 4099; (b) G. Nishida, K. Noguchi, M. Hirano and K.
Tanaka, Angew. Chem. Int. Ed., 2007, 46, 3951; (c) S. Sasaki, K.
Adachi and M. Yoshifuji, Org. Lett. 2007, 9, 1729. (d) J. Mo, D.
Kang, D. Eom, S. H. Kim and P. H. Lee, Org. Lett., 2013, 15, 26;
(e) D. Lecercle, M. Sawicki and F. Taran, Org. Lett. 2006, 8, 4283.
(a) B. Iorga, F. Eymery, D. Carmichael and P. Savignac, Eur. J.
Org. Chem., 2000, 2000, 3103 and references cited therein; For
alternative systems, see (b) K. Jouvin, J. Heimburger and G. Evano,
Chem. Sci., 2012, 3, 756; (c) Y. Wang, J. Gan, L. Liu, H. Yuan, Y.
Gao, Y. Liu and Y. Zhao, J. Org. Chem., 2014, 79, 3678; (d) K.
Jouvin, R. Veillard, C. Theunissen, C. Alayrac, A.ꢀC. Gaumont and
G. Evano, Org. Lett., 2013, 15, 4592; (e) M. Lera and C. J. Hayes,
Org. Lett., 2000, 2, 3873; (f) P. Liu, J. Yang, P. Li and L. Wang,
Appl. Organomet. Chem., 2011, 25, 830; (g) J. Hu, N. Zhao, B.
Yang, G. Wang, L.ꢀN. Guo, Y.ꢀM. Liang and S.ꢀD. Yang, Chem.
Eur. J., 2011, 17, 5516; (h) X. Li, F. Yang, Y. Wu and Y. Wu, Org.
Lett., 2014, 16, 992; (i) Y. Yatsumonji, A. Ogata, A. Tsubouchi and
T. Takeda, Tetrahedron Lett., 2008, 49, 2265; (j) D. Lecerclé, C.
Mothes and F. Taran, Synth. Commun., 2007, 37, 1301; (k) J. E.
Hong, C. W. Lee, Y. Kwon and D. Y. Oh, Synth. Commun., 1996,
26, 1563.
palladiumꢀcatalyzed coupling takes place via a catalytic cycle
involving (i) ligandꢀexchange of Pd(OAc)2 with 1 and an alkyne
to generate the alkynyl(phosphinyl)palladium intermediate 3,
which (ii) undergoes reductive elimination to give the
dehydrocoupling compound 2. Finally, (iii) the reduced
zerovalent palladium is reoxidized by Ag(I) to Pd(II) to complete
the catalytic cycle (Scheme 1).
55
60
5
3
65
70
75
Scheme 1 A proposed mechanism for the palladiumꢀcatalyzed
dehydrocoupling of 1 with terminal alkynes.
10
In summary, a palladiumꢀcatalyzed dehydrocoupling of terminal
alkynes with secondary phosphine oxides was developed. This
new reaction is applicable to a variety of secondary phosphine
oxides and terminal alkynes, and is a general way for the
15 preparation of the valuable alkynylphosphine oxides. Studies on
the mechanism and applications to other substrates are under
way.
80
4
5
85
Notes and references
a State Key Laboratory of Chemo/Biosensing and Chemometrics, College
20 of Chemistry and Chemical Engineering, Hunan University, Changsha
410082, China. E-mail: chentieqiao@hnu.edu.cn
90
b National Institute of Advanced Industrial Science and Technology
(AIST), Tsukuba, Ibaraki 305-8565, Japan. E-mail: libiao-han@aist.go.jp
† Electronic Supplementary Information (ESI) available: General
25 information, experimental procedures, copies of 1H, 13C and 31P NMR
spectra for products.. See DOI: 10.1039/b000000x/
95
‡ Partial financial supports from NFSC (21172062, 21273067,
21373080), the Fundamental Research Funds for the Central Universities
(Hunan University) are acknowledged.
100
105
110
115
120
30
35
40
45
50
1
Recent reviews: (a) C. S. Yeung and V. M. Dong, Chem. Rev.,
2011, 111, 1215; (b) R. Waterman, Chem. Soc. Rev., 2013, 42,
5629; (c) C. Liu, H. Zhang, W. Shi and A. Lei, Chem. Rev., 2011,
111, 1780; (d) S. A. Girard, T. Knauber and C.ꢀJ. Li, Angew. Chem.
Int. Ed., 2014, 53, 74; (e) W. Shi, C. Liu and A. Lei, Chem. Soc.
Rev., 2011, 40, 2761; (f) C.ꢀL. Sun, B.ꢀJ. Li and Z.ꢀJ. Shi, Chem.
Rev., 2011, 111, 1293; (g) Z. Shao and F. Peng, Angew. Chem. Int.
Ed., 2010, 49, 9566; (h) A. Armstrong and J. C. Collins, Angew.
Chem. Int. Ed., 2010, 49, 2282.
6
(a) M. Mahajina, G. B. Quistad and J. E. Casida, Chem. Res.
Toxicol. 1996, 9, 241; (b) K. Van derpoorten and M. E. Migaud,
Org. Lett. 2004, 6, 3461.
Q. Xu and L.ꢀB. Han, J. Organomet. Chem., 2011, 696, 130.
(a) T. Hirao, T. Matsunaga, N. Yamada, Y. Ohshiro and T. Agawa,
Bull. Chem. Soc. Jpn., 1982, 55, 909.
(a) D. E. C. Corbridge, Phosphorus: Chemistry, Biochemistry and
Technology, 6th Ed., CRC Press, New York, 2013; (b) L. D. A
Quin, Guide to Organophosphorus Chemistry, Wiley Interscience.
New York, 2000.
7
8
9
2
Selected examples: (a) T. J. Clark, J. M. Rodezno, S. B.
Clendenning, S. Aouba, P. M. Brodersen, A. J. Lough, H. E. Ruda
and I. Manners, Chem. Eur. J., 2005, 11, 4526; (b) H. Dorn, R. A.
Singh, J. A. Massey, A. J. Lough and I. Manners, Angew. Chem. Int.
Ed., 1999, 38, 3321; (c) H. Dorn, R. A. Singh, J. A. Massey, J. M.
Nelson, C. A. Jaska, A. J. Lough and I. Manners, J. Am. Chem. Soc.,
2000, 122, 6669; (d) R. Shu, L. Hao, J. F. Harrod, H.ꢀG. Woo and E.
Samuel, J. Am. Chem. Soc., 1998, 120, 12988; (e) A. J. Roering, S.
N. MacMillan, J. M. Tanski and R. Waterman, Inorg. Chem., 2007,
46, 6855; (f) J. D. Masuda, A. J. Hoskin, T. W. Graham, C. Beddie,
M. C. Fermin, N. Etkin and D. W. Stephan, Chem. Eur. J., 2006, 12,
8696; (g) V. P. W. Bohm and M. Brookhart, Angew. Chem. Int. Ed.,
10 Since Ag(I) could mediate phosphorylation of indoles with Hꢀ
phosphonates via a radical pathway (H. Wang, X. Li, F. Wu, F. and
B. Wan, Synthesis, 2012, 44, 941), it was assumed that (Ph)2P(O)Ag
and silver phenylacetylide migh be generated in situ and work as the
active species in the coupling reaction (table 1). However, isolated
(Ph)2P(O)Ag (1 equiv) with phenylacetylene (1 equiv) in the
presence of AgBF4 (1 equiv) only gave trace product, while no
product was detected from (Ph)2P(O)Ag (1 equiv) and silver
phenylacetylide (1 equiv). In additon, the palladium catlyzed
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coupling of phenylacetylene with Ph2P(O)H also work efficeintly in
the presence of radical scavanger (1 equiv of butylated
a
hydroxytoluene) to give 75% yield of 2a, that should exclude a
similar radical mechanism.
5
11 T. Chen, C. Guo, M. Goto and L.ꢀB. Han, Chem. Commun. 2013, 49,
7498.
4
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