Pd-catalyzed ligand-free desulfitative Heck reaction with arenesulfinic acid salts under air

Article abstract of DOI:10.1002/aoc.2970

Palladium-catalyzed cross-coupling reactions of various aryl sulfinic acid salts with a wide variety of vinyl substrates have been achieved in good to excellent yields under simple aerobic conditions at 70°C with the assistance of Cu(II) salts. The reaction can be accelerated by the combination of DMSO with THF. The reported Matsuda-Heck type coupling reactions are tolerant to the common functional groups, making these transformations as attractive alternatives to the traditional cross-coupling approaches. Copyright

Full text of DOI:10.1002/aoc.2970

Full Paper
Received: 18 September 2012
Revised: 16 December 2012
Accepted: 26 December 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2970
Pd-catalyzed ligand-free desulfitative Heck
reaction with arenesulfinic acid salts under air
Sai Hua, Ping Xiac, Kai Chengb and Chenze Qib*
Palladium-catalyzed cross-coupling reactions of various aryl sulfinic acid salts with a wide variety of vinyl substrates have been
achieved in good to excellent yields under simple aerobic conditions at 70ꢀC with the assistance of Cu(II) salts. The reaction
can be accelerated by the combination of DMSO with THF. The reported Matsuda–Heck type coupling reactions are tolerant
to the common functional groups, making these transformations as attractive alternatives to the traditional cross-coupling
approaches. Copyright © 2013 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: Pd-catalyzed; desulfitative coupling, Heck coupling
1,4-dioxane, only 15% coupling product was detected. With the
assistance of Cu(OAc)2, the desired product was obtained in
Introduction
Palladium-catalyzed cross-coupling reactions have become a stan-
dard all over the world in both industrial and academic laborato-
ries.[1–12] The Mizoroki–Heck reaction, arguably one of the most
important methods for the creation of carbon–carbon bonds, allows
the coupling of aryl substrate with olefins.[13–19] The Heck coupling
normally takes place between an organohalide (or aryl triflates) and
an alkene typically in the presence of palladium catalyst.[20–27] Subse-
quently, other aryl palladium precursors such as aryl diazonium
salts,[28–33] and diaryl iodonium salts[34,35] have been developed.
Aryl carboxylic acids[36–44] have recently been described as the
source of aryl groups in the Heck reaction. The reactions give access
to various valuable products through the removal of CO2. Recently,
the sodium arenesulfinates have been demonstrated as good
partners in transition-metal-catalyzed chemistry via the release of
SO2. In contrast to stable carboxylic acids (or their salts), the reaction
can proceed under milder conditions with a broader substrate
scope. In 2011, Deng and co-workers reported a Pd-catalyzed
desulfitative Heck-type reaction of aromatic sulfinic acid sodium
salts with various olefins with O2 as the terminal oxidant in 24
h.[45] The presence of phosphane ligand DPEphos in anisole can
significantly enhance the reaction selectivity. When the reaction
was exposed to air, only 50% yields of Heck-type products were
obtained, and 30% of conjugate addition product was detected.
Soon after, Wang and co-workers developed an efficient protocol
for the desulfitative Heck-type reaction of aryl sulfinic acids with a
variety of alkenes in the presence of a catalytic amount of Pd
(OAc)2 and Cu salts as oxidant under 100ꢀC in 24 h,[46,47] broaden-
ing the scope of Pd-catalyzed coupling reactions. Further research
considering more convenient and more efficient methods is still
important. Herein, we report our results concerning readily
available aromatic sulfinic acid sodium salts in Heck coupling under
aerobic conditions under 70ꢀC for 6 h without ligands or bases.
35% yield (Table 1, entry 1). Considering that the solubility of
sodium salt in 1,4-dioxane was rather poor, we selected many
solvents to test the effect on conversion. The selection of solvents
revealed that polar aprotic solvents like DMSO and DMF were
effective in the reaction, affording yields of 70% and 62%
respectively (Table 1, entries 2 and 3), and non-polar solvents
were negative (Table 1, entries 4–7). In our investigation, the
mixture of organic solvent with DMSO can afford better results,
and the combination of DMSO with THF in a ratio of 1:1 was the
best (Table 1, entries 8–12). We further studied the ratio of DMSO
and THF (the range was changed from 9:1 to 1:9) and yields
ranged from 77% to 93% (Table 1, entries 13–20). Finally, we
chose DMSO–THF (1:2) as the model solvent for this reaction.
Various sources of inexpensive and commercially available
palladium complexes and copper reagents were screened for
the reaction and the results are summarized in Table 2. Examina-
tion of Table 2 shows that the isolated cross-coupling yields are
significantly influenced by the palladium catalysts employed.
Among the palladium catalysts screened, the best performances
were obtained for palladium acetate [Pd(OAc)2], palladium
chloride (PdCl2) and palladium iodide (PdI2), with isolated cross-
coupling yields all over 85% (Table 2, entries 1–3). The cross-
coupling reactions were also examined with several phosphine
ligand-chelated palladium complexes (Table 2, entries 4–7) under
*
Correspondence to: Chenze Qi, Zhejiang Key Laboratory of Alternative Technol-
ogies for Fine Chemicals Process, University of Shaoxing, Shaoxing, Zhejiang
Province 312000, People’s Republic of China. E-mail: qichenze@usx.edu.cn
a College of Materials Science and Chemical Engineering, Ningbo University,
Ningbo 310014, People’s Republic of China
b Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process,
University of Shaoxing, Shaoxing, Zhejiang, Province 312000, People’s Republic
of China
Results and Discussion
When the reaction of phenylsulfinic acid sodium salt with n-butyl
c
College of Chemistry and Chemical Engineering, Henan University of Technology,
acrylate was carried out using Pd(OAc)2 (5 mol%) as catalysts in
Zhengzhou 450001, People’s Republic of China
Appl. Organometal. Chem. 2013, 27, 188–190
Copyright © 2013 John Wiley & Sons, Ltd.

Desulfitative ligand-free Heck reaction with arylsulfinate sodium
Table 1. Solvent selection for Pd-catalyzed Matsuda–Heck coupling
of sodium benzenesulfinate with butyl acrylatea
N2 atmosphere, but all led to relatively lower isolated yields
(45–80%). The relatively lower cross-coupling yields suggest
that the phosphine ligands may not be necessary for the
palladium-catalyzed cross-coupling of aryl sulfinic acid salts. In
other words, the palladium-catalyzed reactions could be
performed under aerobic conditions, greatly simplifying the
experimental studies. Other Pd catalysts such as Pd(PhCN)2Cl2
showed good catalytic activity, affording a yield of 88%
(Table 2, entry 8). Many copper(II) salts have been tested in this
transformation, and the results are in Table 2 (entries 9–12).
The cross-coupling yields in the range 62–86% were obtained.
Interestingly, only 36% yield was isolated in the presence of
Cu(I) salt (Table 2, entry 13). Other oxidants have also been
tested. AgOAc showed more reactivity than (PhCO2)2 and
benzoquinone (Table 2, entries 14–16). Notably, the transforma-
tion was not accelerated by the protection of pure oxygen
(Table 2, entry 17).
Entry
Solvent
Yield Entry
(%)b
Solvent
Yield
(%)b
1
2
3
4
5
6
7
8
9
10
1,4-Dioxane
35
70
62
20
10
—
35
11 DMSO–hexane (1:1) 65
DMSO
DMF
12 DMSO–THF (1:1)
13 DMSO–THF (9:1)
14 DMSO–THF (4:1)
15 DMSO–THF (3:1)
16 DMSO–THF (2:1)
17 DMSO–THF (1:2)
18 DMSO–THF (1:3)
19 DMSO–THF (1:4)
20 DMSO–THF (1:9)
80
79
84
89
87
93
86
86
77
Toluene
CH3CN
n-Hexane
THF
The optimized reaction conditions can be applied to the Pd(OAc)2-
catalyzed cross-coupling of aryl sulfinic acid salts with a wide variety
of vinyl substrates (Table 3). Excellent cross-coupling yields
(91%ꢁ 3%) can be obtained for methyl acrylate and butyl acrylate
(Table 3, entries 1–3). Although excellent stereoselectivity was
detected in most cases, the coupling of sodium benzenesulfinate
DMSO–dioxane (1:1) 78
DMSO–toluene (1:1) 66
DMSO–CH3CN (1:1)
72
aReaction conditions: sodium benzenesulfinate (0.5 mmol), butyl
acrylate (0.6 mmol), Pd(OAc)2 (5 mol%), Cu(OAc)2 (0.5 mmol), solvent
(1.0 ml) at 70ꢀC for 6 h unless otherwise indicated.
bIsolated cross-coupling yield; v/v ratio is shown in parentheses.
Table 3. Pd-catalyzed Matsuda–Heck coupling of aryl sulfinic acid
salts with vinyl substratea
Table 2. Metal and oxidant selection for Matsuda–Heck coupling of
sodium benzenesulfinate with butyl acrylatea
Entry
R
R0
R00
Yield (%)b
1
H
H
H
H
COOnꢂBu
COOMe
93
2
88
3
p-Me
H
H
COOMe
91
Entry
Catalyst
PdCl2
Oxidant
Cu(OAc)2
Yield (%)b
4
H
CN
96 (E/Z = 65:35)
1
90
85
5
H
H
Ph
83
90
91
81
93
64
86
89
90
86
87
83
85
76
78
73
57
2
PdI2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuCl2
6
p-Me
m-Me
o-Me
m-Me
o-Me
p-OMe
m-OMe
p-Cl
H
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
COOnꢂBu
3
Pd(OAc)2
PdCl2(PPh3)3
Pd(PCy3)2Cl2
Pd(dppf)Cl2
Pd(PPh3)4
Pd(PhCN)2Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
93
7
H
4
80c
45c
70c
69c
88c
62
8
H
5
9
m-Me
o-Me
H
6
10
11
12
13
14
15
16
17
18
19
20
21
7
8
H
9
H
10
11
12
13
14
15
16
17
Cu(acac)2
Cu(OTf)2
Cu(TFA)2
CuI
71
p-Br
H
86
p-I
H
64
m-Cl
m-Br
o-Cl
H
36
H
AgOAc
81
H
(PhCO2)2
Benzoquinone
O2
42
o-Br
H
16
91d
p-NO2
o-NO2
H
H
aReaction conditions: sodium benzenesulfinate (0.5 mmol), butyl acrylate
(0.6 mmol), catalyst (5 mol%), oxidant (0.5 mmol), DMSO–THF = 1:2
(1.0 ml) at 70ꢀC for 6 h unless otherwise indicated.
aReaction conditions: sodium arylsulfinate (0.5 mmol), vinyl substrate
(0.6 mmol), Pd(OAc)2 (5 mol%), Cu(OAc)2 (0.5 mmol), DMSO–THF = 1:2
(1.0 ml) at 70ꢀC for 6 h unless otherwise indicated.
bIsolated cross-coupling yield. All products are known compounds and
related characterization and references have been given in supporting
information.
bIsolated cross-coupling yield.
cThe reaction was performed under N2 atmosphere.
dThe reaction was performed under O2 atmosphere.
Appl. Organometal. Chem. 2013, 27, 188–190
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

S. Hu et al.
Acknowledgments
This study was supported by the National Science Foundation of
China (Grant No. 21172149) and the Science Technology Depart-
ment of Zhejiang Province (Grant No. 2012R10014-15).
References
[1] V. Farina, Adv. Synth. Catal. 2004, 346, 1553.
[2] H.-U. Blaser, A. Indolese, F. Naud, U. Nettekoven, A. Schnyder, Adv.
Synth. Catal. 2004, 346, 1583.
[3] A. Zapf, M. Beller, Chem. Commun. 2005, 431.
[4] K. C. Nicolaou, P. G. Bulger, D. Sarlah, Angew. Chem. Int. Ed. 2005, 44,
4442.
[5] G. Zeni, R. C. Larock, Chem. Rev. 2006, 106, 4644.
[6] L. Yin, J. Liebscher, Chem. Rev. 2007, 107, 133.
[7] M. Zeng, Y. Du, L. Shao, C. Qi, X. M. Zhang, J. Org. Chem. 2010,
75, 2556.
[8] Transition Metals for Organic Synthesis: Building Blocks and Fine Che-
micals (2nd edn), (Eds.: M. Beller, C. Bolm), Wiley-VCH, Weinheim,
2004.
[9] Handbook of Organopalladium Chemistry for Organic Synthesis, (Eds.:
E. Negishi, A. de Meijere), Wiley, New York, 2002.
[10] J. Hassan, M. Sévignon, C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev.
2002, 102, 1359.
[11] I. Cepanec, Synthesis of Biaryls, Elsevier, Amsterdam, 2004.
[12] J. Tsuji, Palladium Reagents and Catalysts (2nd edn), Wiley, New York,
2004.
[13] T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 581.
[14] R. F. Heck, J. P. Nolley, J. Org. Chem. 1972, 37, 2320.
[15] M. Oestreich, The Mizoroki–Heck Reaction, Wiley, Chichester, 2009.
[16] A. de Meijere, F. E. Meyer, Angew. Chem. Int. Ed. 1994, 33, 2379.
[17] W. Cabri, I. Candiani, Acc. Chem. Res. 1995, 28, 2.
[18] G. T. Crisp, Chem. Soc. Rev. 1998, 27, 427.
[19] I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009.
[20] N. J. Whitcombe, K. K. Hii, S. E. Gibson, Tetrahedron 2001, 57, 7449.
[21] A. F. Littke, G. C. Fu, Angew. Chem. Int. Ed. 2002, 41, 4176.
[22] A. F. Littke, G. C. Fu, Org. Synth. 2004, 81, 63.
[23] F. Alonso, I. P. Beletskaya, M. Yus, Tetrahedron 2005, 61, 11771.
[24] N. T. S. Phan, M. Van der Sluys, C. W. Jones, Adv. Synth. Catal. 2006,
348, 609.
Scheme 1. Mechanism Proposed
with the substrate of acrylonitrile obtained a mixture of E-isomer
and Z-isomer with an isolation yield of 96% (E/Z = 65:35, deter-
mined by 1H NMR) (Table 3, entry 4). Otherwise, styrene derivatives
are also coped with this condition to afford linear (E)-stilbene in
good yield (Table 3, entry 5). The o-, m- and p-methyl substitution
did not affect the reaction obviously and showed good reactivity
(Table 3, entries 6–8). Disubstituent on aryl sulfinic acid salts can
also proceed smoothly, and 64% yield of product can be obtained
when encountering hindrance by two neighboring methyl groups
(Table 3, entries 9 and 10). Nevertheless, excellent coupling yield
(86% and 89%) could still be obtained when coupled with sodium
4- and 3-methoxybenzenesulfinate (entries 11 ~ 12 of Table 3,
entries 11 and 12). Notably, iodo-, bromo- or chloro- groups
seem to have trivial effects on the isolated cross-coupling yield
(Table 3, entries13–19) no matter the position of o-, m- and p-. The
phenomenon reveals that this transformation showed outstanding
functional group tolerance, as well as excellent chemoselectivity.
The introduction of an electron-withdrawing group like nitro- has
hindered the cross-coupling (Table 3, entries 20 and 21).
A possible mechanism for our desulfinylative CꢂC cross-coupling
reaction of sulfinic acid salts with vinyl substrates is shown in
Scheme 1. The DMSO molecule could coordinate with the Pd center
to stabilize/activate the catalyst to replace ancillary ligand. Step (i)
involves the nucleophilic attack of ArSO2 anion on Pd(II)X2 to afford
intermediate A. In step (ii), the ArꢂPd(II)ꢂX intermediate B (X= OAc)
was formed with concomitant loss of SO2. The addition of interme-
diate B to vinyl substrates generated intermediate C and then was
converted to HꢂPd(II)ꢂX with the release of desired products. In
step (iii), the reductive elimination from the Pd(II) complex affords
the Pd(0), and the Pd(0) catalyst is reoxidized to Pd(II) by Cu(OAc)2,
thus closing the catalytic cycle. The intermediate C was stabilized
by conjugate effect and E-isomer dominated.
[25] K. Köhler, S. S. Pröckl, W. Kleist, Curr. Org. Chem. 2006, 10, 1585.
[26] A. F. Schmidt, A. Al Halaiqa, V. V. Smirnov, Synlett 2006, 2861.
[27] G. P. McGlacken, I. J. S. Fairlamb, Eur. J. Org. Chem. 2009, 4011.
[28] A. Roglans, A. Pla-Quintana, M. Moreno-Mañas, Chem. Rev. 2006, 106,
4622.
[29] A. A. Sabino, A. H. L. Machado, C. R. D. Correia, M. N. Eberlin, Angew.
Chem. Int. Ed. 2004, 43, 2514.
[30] K. Peixoto da Silva, M. N. Godoi, C. R. D. Correia, Org. Lett. 2007, 9,
2815.
[31] F. X. Felpin, J. Coste, C. Zakri, E. Fouquet, Chem. Eur. J. 2009, 15, 7238.
[32] A. V. Moro, F. S. P. Cardoso, C. R. D. Correia, Org. Lett. 2009, 11, 3642.
[33] B. Schmidt, F. Hoelter, Chem. Eur. J. 2009, 15, 11948.
[34] B. R. Vaddula, A. Saha, J. Leazer, R. S. Varma, Green Chem. 2012 (in press).
[35] J. Li, L. Liu, Y. Zhou, S. Xu, RSC Adv. 2012, 2, 3207.
[36] A. G. Myers, D. Tanaka, M. R. Mannion, J. Am. Chem. Soc. 2002, 124, 11250.
[37] D. Tanaka, A. G. Myers, Org. Lett. 2004, 6, 433.
[38] D. Tanaka, S. P. Romeril, A. G. Myers, J. Am. Chem. Soc. 2005, 127,
10323.
[39] P. Hu, J. Kan, W. Su, M. Hong, Org. Lett. 2009, 11, 2341.
[40] S.-L. Zhang, Y. Fu, R. Shang, Q.-X. Guo, L. Liu, J. Am. Chem. Soc. 2010,
132, 638.
[41] Z. Hu, S. Huang, W. Su, M. Hong, Org. Lett. 2010, 12, 4992.
[42] A. Maehara, H. Tsurugi, T. Satoh, M. Miura, Org. Lett. 2008, 10, 1159.
[43] Z. Li, S. L. Zhang, Y. Fu, R. Shang, Q.-X. Guo, L. Liu, J. Am. Chem. Soc.
2009, 131, 8815.
Conclusion
The [Pd(OAc)2]-catalyzed cross-coupling of aryl sulfinic acid
salts with vinyl substrates has been achieved under mild reaction
conditions. The high efficiency and reactivity of the aryl sulfinic acid
salts could be attributed to the formation of active Pd0 species via
the release of SO2 during the catalytic cycle. The mild reaction
conditions combined with the widely available sodium arylsulfinate
enable this transformation to be an attractive alternative to the
Heck-type cross-coupling.
[44] Z. Sun, J. Zhang, P. Zhao, Org. Lett. 2010, 12,992.
[45] X. Zhou, J. Luo, J. Liu, S. Peng, G.-J. Deng, Org. Lett. 2011, 13, 1432.
[46] G.-W. Wang, T. Miao, Chem. Eur. J. 2011, 17, 5787.
[47] T. Miao, G.-W. Wang, Chem. Commun. 2011, 47, 9501.
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Appl. Organometal. Chem. 2013, 27, 188–190