Copper-free palladium-catalysed desulfinative homocoupling of sodium arylsulfinates under mild and aerobic conditions

Article abstract of DOI:10.3184/174751916X14798135087600

A Pd(II)-catalysed homocoupling of sodium arylsulfinates has been successfully achieved under mild conditions. This transformation is a new method for the homocoupling reaction of sodium arylsulfinates, thus providing an alternative synthesis of symmetric biaryls. The reported homocoupling reaction is tolerant to many common functional groups, such as ester, halo, cyano and nitro and works well in the presence of electron-donating and electron-withdrawing substituents. Notably, the reported desulfinative homocoupling does not require Cu salts, ligands and bases, making this newly developed transformation attractive.

Full text of DOI:10.3184/174751916X14798135087600

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 41 JANUARY, 1–3
RESEARCH PAPER 1
Copper-free palladium-catalysed desulfinative homocoupling of sodium
arylsulfinates under mild and aerobic conditions
Wei Zhang
Department of Chemistry and Chemical Engineering, Xinxiang University, Xinxiang 453003, P.R. China
A Pd(II)-catalysed homocoupling of sodium arylsulfinates has been successfully achieved under mild conditions. This transformation is
a new method for the homocoupling reaction of sodium arylsulfinates, thus providing an alternative synthesis of symmetric biaryls. The
reported homocoupling reaction is tolerant to many common functional groups, such as ester, halo, cyano and nitro and works well in the
presence of electron-donating and electron-withdrawing substituents. Notably, the reported desulfinative homocoupling does not require
Cu salts, ligands and bases, making this newly developed transformation attractive.
Keywords: sodium arylsulfinates, Pd(II)-catalysis, desulfinative homocoupling, symmetric biaryls
Table 1 Homocoupling of arylsulfinates
Transition-metal-catalysed cross-coupling reactions are one of
the most studied and applied areas of synthetic methodology and
have been established as indispensable tools for carbon–carbon
bond formation in modern organic synthesis.1–4 Procedures
for the preparation of symmetrical biaryl compounds began
with the Ullmann coupling5 more than 100 years ago which
has evolved into one of the most investigated aryl–aryl bond-
forming reactions. Inspired by the homocoupling reaction of
aryl halides,6–7 alternative approaches to the synthesis of biaryls,
involving homocoupling of aryl metal reagents,8–9 dimerisation
of organoborane reagents10–11 and decarboxylative dimerisation
of aryl carboxylic acids12 as well as desulfinative homocoupling
of aryl sulfonyl compounds have been developed.13–15 However,
the homocoupling of arylsulfinic acid salts has not been well-
established yet.
Arylsulfinic acid salts are stable and easy-to-handle reagents,
which show great potential as aryl sources for the synthesis of
various aromatic compounds. Density functional theory (DFT)
calculations have revealed that C–SO2R bond-dissociation
enthalpies (BDEs) are much lower than the corresponding
C–CO2R BDEs, which suggests that arylsulfinic acids should
be more reactive substrates than aryl carboxylic acids.16 In
recent years, arylsulfinic acids have been widely used for
Heck,17–18 Hiyama19 and Suzuki cross-coupling reactions,20
C–H bond activations21–25 and additions to triple bonds.26–30 The
homocoupling of arylsulfinic acid salts as an alternative to the
traditional Ullmann coupling was only reported recently. In
2011, You and co-workers31 first reported a palladium-catalysed
desulfinative homocoupling of sodium benzenesulfinate with
an excess of Cu(OAc)2 under N2 in a yield of 81%. Next, Luo and
co-workers32 reported a palladium-catalysed homocoupling of
arylsulfinates in water employing a Cu2O catalyst together with
oxygen as oxidant. The yields of biaryls were in the range 35–
90%. In 2014, Forgione and co-workers33 developed a Pd(II)-
Johnphos catalytic system for the desulfinative homocoupling
reaction of arylsulfinates. Stoichiometric copper(II) chloride
along with caesium carbonate was crucial for the transformation.
The authors then used (2,2,6,6-tetramethylpiperidin-1-yl)oxyl
(TEMPO) as co-catalyst in the presence of oxygen to enhance
the catalytic activity. Despite these advances, room still exists
for developing simple and convenient approaches which
proceed under milder conditions. We report here an effective
and practical protocol for the preparation of symmetric biaryls
from various arylsulfinates. The reaction proceeds under very
mild conditions and is tolerant of a broad range of functional
groups without the addition of Cu salt, ligands and bases under
air (Table 1).
Ref.
31
32
33
33
Reaction conditions
Pd(OAc)2/Cu(OAc)2/TBAB/N2
PdCl2/Cu2O/O2
PdCl2/Johnphos/CuCl2/Cs2CO3
PdCl2/Johnphos/TEMPO/CaO
Pd(OAc)2/DTBP
Yield/%
81
35–90
0–70
26–85
78–96
Results and discussion
The reaction of sodium benzenesulfinate was chosen as a
model system for optimisation studies (Table 2). Initially, the
reaction was carried out in CH3CN at 60 °C for 12 h in the
presence of palladium(II) acetate (1 mol%) and Cu(OAc)2
(2 equiv.) as an oxidant. However, only tiny amounts of the
desired homocoupling product were obtained and instead a
large amount of diphenyl sulfone by-product (1b) was formed
(Table 2, entry 1).34–37 Although the addition of other Cu salts
and Ag salts as oxidants also failed to effect desulfinative
homocoupling (Table 2, entries 2–10), the use of Ag salts
was observed to diminish the amount of diphenyl sulfone
(Table 2, entries 7–10). When benzoyl peroxide (BPO) was
used as an oxidant (see SAFETY WARNING in Experimental
section), we were pleased to find that biphenyl was obtained
in 56% yield without the detection of any diphenyl sulfone by-
product (Table 2, entry 11). Other peroxides, such as tert-butyl
peroxyacetate (TBPA), tert-butyl peroxybenzoate (TBPB),
and tert-butyl peroxypivalate (TBPV) were significantly more
effective, whereas di-tert-amyl peroxide (DTAP) and tert-
amyl hydroperoxide (TAHP) gave comparable results (Table 2,
entries 12–16). tert-Butyl cumyl peroxide (TBCP) and dicumyl
peroxide (DCP) were ineffective for the generation of 1a (Table
2, entries 17 and 18). No product was detected when the model
reaction was performed with tert-butyl hydroperoxide (TBHP)
(Table 2, entry 19). Among those oxidants tested, di-tert-butyl
peroxide (DTBP) afforded the highest yield of biphenyl (1a)
(Table 2, entry 20).
Our investigation then focused on the effect of different
transition-metal catalysts and solvents on the model reaction
and the results are summarised in Table 3. Several Pd(0) salts
were screened in the presence of DTBP as oxidant in CH3CN.
Pd2(dba)3 and Pd(Ph3P)4 did not exhibit catalytic activity
(Table 3, entries 1 and 2). Reactions catalysed by other Pd
salts, such as [Pd(C3H5)Cl]2, Pd(TFA)2 and PdCl2, either did
not proceed or gave poor yields (Table 3, entries 3–5). The
use of Pd(CH3CN)2Cl2 and Pd(PhCN)2Cl2 showed relatively
higher efficiency and 82–87% yields of biphenyl were obtained
* Correspondent. E-mail: xinxiangzhangwei@126.com

2 JOURNAL OF CHEMICAL RESEARCH 2016
Table 2 Influence of the oxidant in the homocoupling of sodium
Table 3 Influence of the catalysts and solvents on the homocoupling of
benzenesulfinatea,b
sodium benzenesulfinatea
catalyst
Pd(OAc)2
oxidant
O
DTBP
SO2Na
Na
SO2
S
CH3CN
solvent
O
1b
60 o air
,
60 oC air
1a
C,
Entry
1
2
3
4
5
6
7
8
Catalyst
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Mesitylene
tert-AmOH
DCE
DMSO
NMP
DME
CPME
THF
Yield/%b
–
Entry Oxidant
Yield of 1a(1b)/% Entry Oxidant Yield of 1a/%
Pd2(dba)3
Pd(Ph3P)4
[Pd(C3H5)Cl]2
Pd(TFA)2
PdCl2
Pd(CH3CN)2Cl2
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
Pd(OAc)2
1
2
3
4
5
6
7
8
9
10
Cu(OAc)2
CuCl2
8(74)
10(65)
5(60)
11
12
13
14
15
16
17
18
19
20
BPO
56
75
77
72
70
68
52
57
–
–
–
TBPA
TBPB
TBPV
DTAP
TAHP
TBCP
DCP
CuBr2
53
60
82
87
92
–
Cu(OTf)2
Cu(TFA)2
CuI
14(71)
18(61)
–(–)
AgOAc
Ag2CO3
AgOTf
AgNO3
29(23)
26(27)
39(40)
33(27)
9
10
11
12
13
14
15
16
17
–
TBHP
DTBP
83
87
82
89
85
88
81
81
aReaction conditions: sodium benzenesulfinate (1 mmol), Pd(OAc)2 (1 mol%), oxidant
(0.5 mmol), CH3CN (1.0 ml) at 60 oC for 12 h under air.
bIsolated yield.
The abbreviations used in the table are: BPO (benzoyl peroxide), TBPA (tert-butyl
peroxyacetate), TBPB (tert-butyl peroxybenzoate), TBPV (tert-butyl peroxypivalate),
DTAP (di-tert-amyl peroxide), TAHP (tert-amyl hydroperoxide), TBCP (tert-butyl cumyl
peroxide), DCP (dicumyl peroxide), TBHP (tert-butyl hydroperoxide), DTBP (di-tert-butyl
peroxide). See SAFETY WARNING in Experimental section.
Diglyme
aReaction conditions: sodium benzenesulfinate (1 mmol), catalyst (1 mol%), DTBP
(0.5 mmol), solvent (1.0 ml) at 60 oC for 12 h
bIsolated yield.
Table 4 Homocoupling of various sodium arylsulfinatesa
(Table 3, entries 6 and 7). Pd(OAc)2 showed the highest activity,
providing biphenyl in 92% yield (Table 3, entry 8). In the next
stage, we examined the effect of the solvent on the reaction (Table
3, entries 9–17). The reaction did not proceed in mesitylene or tert-
AmOH (tert-amyl alcohol) (Table 3, entries 9 and 10). Among the
other solvents [ 1,2-dichloroethane (DCE), DMSO, N-methyl-2-
pyrrolidone (NMP) and dimethoxyethane (DME)] tested (Table
3, entries 11–17), DME gave the best result. Three additional
ethereal solvents [CPME (cyclopentyl methyl ether), diglyme and
THF] were surveyed without leading to any improvement (Table 3,
entries 15–17). Further attempted optimisation, such as increasing
the temperature of the reaction and doubling the reaction time, did
not lead to increased yields. Thus, the optimised conditions were
Pd(OAc)2 as the catalyst and DTBP as the oxidant in CH3CN at 60
°C for 8 h.
Furthermore, considerable efforts have been made to test the
substrate scope of this reaction under the optimised reaction
conditions. We applied this catalytic system to various sodium
arylsulfinates (Table 4). Notably, this reaction showed good
compatibility with different groups on the aryl ring. Sodium
benzenesulfinates with p-MeO, p-Me and p-tert-Bu substituents
were well tolerated, affording the corresponding homocoupling
products in 93, 90 and 94% yields (Table 4, entries 1–3).
Sodium arylsulfinates with electron-withdrawing substituents
such as COOMe, CN and CF3 groups were also good coupling
partners (Table 4, entries 5–7). Halogenated sulfinates such as
p-FC6H4SO2Na, p-Cl C6H4SO2Na and p-BrC6H4SO2Na underwent
homocoupling smoothly in good yields (Table 4, entries 8–10).
Sodium 3,4-dimethoxybenzenesulfinate reacted efficiently to
produce 3,3′,4,4′-tetramethoxy-1,1’-biphenyl in 95% yield (Table
4, entry 11). In addition, ortho- and meta-substituted arylsulfinates
were also well tolerated, generating the desired coupling products
in moderate to good yields (Table 4, entries 12–17). 3-Nitro-,
3-carboxymethyl- and 3-cyano-phenylsulfinates were converted
into the corresponding biaryls in 89, 83 and 84% yields,
Pd(OAc)2
DTBP
R
Na
SO2
R
R
CH3CN
60 o air
C,
Entry
1
2
3
4
5
6
7
8
R
Yield/%b
M.p./°C
175–176
124–125
127–129
67–68
214–216
234–236
83–84
M.p.lit/°C
173–17438
122–12438
128–12911
67–6938
214–21511
23439
4-CH3OC6H4
4-CH3C6H4
4-t-BuC6H4
C6H5
4-CH3OOCC6H4
4-CNC6H4
4-CF3C6H4
4-FC6H4
4-ClC6H4
93
92
94
86
88
82
83
89
87
85
95
89
83
84
75
77
87
85
84
89
83
84
88
79
82–8311
88–90
89–9011
149–15438
168–17038
130–13211
201–20238
102–10311
197–19911
156–15738
1840
9
148–150
165–166
131–132
201–203
102–104
197–199
155–156
Liquid
121–122
183–184
145–146
186–188
32–33
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4-BrC6H4
3,4-(CH3O)2C6H3
3-NO2C6H4
3-CH3OOCC6H4
3-CNC6H4
2-CH3OC6H4
2-CH3C6H4
2-NO2C6H4
2-naphthyl
1-naphthyl
9-phenanthryl
2-thienyl
12039
180–18238
143–14441
186–18711
3239
3-pyridyl
4-pyridyl
C6H5CH=CH
64–65
110–111
150–151
64–6511
110–11242
15139
aReaction conditions: sodium arylsulfinate (1 mmol), catalyst (1 mol%), DTBP (0.5 mmol),
CH3CN (1.0 ml) at 60 oC for 12 h.
bIsolated yield.

JOURNAL OF CHEMICAL RESEARCH 2016 3
Afterwards, the reaction solution was filtered through a filter paper and
the organic phase was evaporated under reduced pressure at 40 oC. The
residue was purified on a SiO2 column (ethyl acetate/hexane = 1:20) to
afford the desired product.
t-BuOOt-Bu
Ar-Ar
Pd(0)
C
Electronic Supplementary Information
Pd(II)
ArPd Ar
(II)
O
S
The ESI (spectroscopic data and other details of the products)
is available through
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
Na
SO2
Ar
O
O
S
Received 15 July 2016; accepted 12 November 2016
Paper 1604195 doi: 10.3184/174751916X14798135087600
Published online: 16 January 2016
ArSO2Na
O
Ar
ArPd
(II)
A
Pd
(II)
B
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Based on our experimental results and the literature,16 a possible
mechanism for the Pd-catalysed desulfinative homocoupling
reactions of arylsulfinates is summarised in Scheme 1. The first
reaction step involves the nucleophilic attack of the ArSO2 anion on
Pd(OAc)2 to form the four-membered transition state ArSO2Pd(II)
(Scheme 1, A) which was proposed by Yu et al.,16 followed by
the formation of an ArPd(II) intermediate (Scheme 1, B) and
concomitant loss of sulfur dioxide (SO2). Subsequent nucleophilic
attack with ArSO2Na on intermediate B, formed after loss of SO2 by
heating, affords ArPd(II)Ar (Scheme 1, C). Reductive elimination
of the desulfinative homocoupling product leads to the formation of
a Pd(0) species, which is oxidised to the oxidative Pd(II) species by
DTBP to complete the catalytic cycle.
In summary, the Pd-catalysed homocoupling of the arylsulfinates
provides a versatile method for the construction of symmetric biaryl
motifs. The methodology complements more established methods
such as the Ullmann coupling. Considering the attractive features
of arylsulfinate substrates and the coupling reaction’s broad scope,
we expect this methodology will prove useful in synthesis and will
further encourage the development of symmetric biaryl synthetic
transformations.
Experimental
All solvents were purified and dried prior to use.43 Arylsulfinate salts were
obtained from the corresponding arylsulfonyl chlorides.44 All materials
were purchased from common commercial sources and used without
additional purification.
SAFETY WARNING: All peroxides should be handled with
appropriate precautions after their explosive nature has been
assessed from the literature.
Synthesis of the products; general procedure
A mixture of the sodium arylsulfinate (1 mmol), Pd(OAc)2 (1 mol%)
and DTBP (0.5 mmol) was stirred at 60 oC for 12 h in CH3CN (1 mL).
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