Heterogeneous copper-catalyzed oxidative coupling of oxime acetates with sodium sulfinates: An efficient and practical synthesis of β-keto sulfones

Article abstract of DOI:10.1002/aoc.5001

An efficient and practical route to β-keto sulfones has been developed through heterogeneous oxidative coupling of oxime acetates with sodium sulfinates by using an MCM-41-supported Schiff base-pyridine bidentate copper (II) complex [MCM-41-Sb,Py-Cu (OAc)₂] as the catalyst and oxime acetates as an internal oxidant, followed by hydrolysis. The reaction generates a variety of β-keto sulfones in good to excellent yields. This new heterogeneous copper (II) catalyst can be easily prepared via a simple procedure from readily available and inexpensive reagents and exhibits the same catalytic activity as Cu (OAc)₂. MCM-41-Sb,Py-Cu (OAc)₂ is also easy to recover and is recyclable up to eight times with almost consistent activity.

Full text of DOI:10.1002/aoc.5001

Received: 4 January 2019
DOI: 10.1002/aoc.5001
Revised: 25 April 2019
Accepted: 28 April 2019
F U L L P A P E R
Heterogeneous copper‐catalyzed oxidative coupling of
oxime acetates with sodium sulfinates: An efficient and
practical synthesis of β‐keto sulfones
Jianhui Xia1 | Xue Huang1 | Shengyong You2 | Mingzhong Cai1
1 Key Laboratory of Functional Small
An efficient and practical route to β‐keto sulfones has been developed through
Organic Molecule, Ministry of Education
and College of Chemistry & Chemical
heterogeneous oxidative coupling of oxime acetates with sodium sulfinates by
Engineering, Jiangxi Normal University,
using an MCM‐41‐supported Schiff base‐pyridine bidentate copper (II) complex
Nanchang 330022, China
[MCM‐41‐Sb,Py‐Cu (OAc)2] as the catalyst and oxime acetates as an internal
oxidant, followed by hydrolysis. The reaction generates a variety of β‐keto sul-
fones in good to excellent yields. This new heterogeneous copper (II) catalyst
can be easily prepared via a simple procedure from readily available and
inexpensive reagents and exhibits the same catalytic activity as Cu (OAc)2.
MCM‐41‐Sb,Py‐Cu (OAc)2 is also easy to recover and is recyclable up to eight
times with almost consistent activity.
2 Institute of Applied Chemistry, Jiangxi
Academy of Sciences, Nanchang 330029,
China
Correspondence
Shengyong You, Institute of Applied
Chemistry, Jiangxi Academy of Sciences,
Nanchang 330029, China.
Email: ysygood1981@163.com Mingzhong
Cai, Key Laboratory of Functional Small
Organic Molecule, Ministry of Education
and College of Chemistry & Chemical
Engineering, Jiangxi Normal University,
Nanchang 330022, China.
KEYWORDS
copper, heterogeneous catalysis, oxidative coupling, oxime acetate, β‐Keto sulfone
Email: caimzhong@163.com
Funding information
Key Laboratory of Functional Small
Organic Molecule, Ministry of Education,
Grant/Award Number: No. KLFS‐KF‐
201704 KLFS‐KF‐201704; National Natu-
ral Science Foundation of China, Grant/
Award Number: No. 21462021 21462021
1 | INTRODUCTION
Traditional methods involve alkylation of sodium
sulfinates with either α‐haloketones or α‐tosyloxyke-
β‐Keto sulfones are one of the most valuable sulfur‐
containing compounds owing to their unique biological
properties and present in a large number of natural prod-
ucts as key structural motifs.[1] They have been widely
used as important synthetic intermediates in the synthesis
of natural products[2] and various important structural
molecules such as disubstituted acetylenes, olefins,
allenes, vinylsulfones, β‐hydroxy sulfone, ketones, quino-
lines, and polyfunctionalized 4H‐pyrans.[3] Their wide-
spread utilities have driven the development of many
strategies for the construction of β‐keto sulfones.
tones,[4] oxidation of β‐keto sulfides, β‐keto sulfoxides
and β‐hydroxy sulfones,[5] reactions of diazo sulfones with
aldehydes,[6] sulfonylation of alkyl ketones or silyl enol
ethers,[7] and acylation of alkyl sulfones.[8] However, most
of them suffer from some drawbacks such as the use of the
pre‐functionalized materials, relatively complicated or
harsh conditions, limited substrate scope, and undesirable
byproducts. Recently, some efficient and alternative
approaches for the synthesis of β‐keto sulfones have been
reported, including reactions of alkynes or 2‐arylacrylic
acids with sulfinic acids,[9] reactions of olefins with
Appl Organometal Chem. 2019;e5001.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5001

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XIA ET AL.
sulfinic acids, sodium sulfinates or sulfonyl hydrazides,[10]
photoinduced rearrangement of vinyl tosylates,[11]
decarboxylative hydroxysulfonylation of arylpropiolic
acids with sodium sulfinates,[12] photo‐induced sulfon-
ylative coupling of aryl/alkyl halides, sulfur dioxide and
silyl enolates.[13] Despite impressive progresses made in
this area, the development of new and more efficient
methods for the construction of β‐keto sulfones still
remains highly desirable.
successful application to oxidative coupling of oxime ace-
tates with sodium sulfinates leading to β‐keto sulfones in
good to excellent yields (Scheme 1).
2 | RESULTS AND DISCUSSION
A series of MCM‐41‐supported Schiff base‐pyridine
bidentate copper(I) or (II) complexes [MCM‐41‐Sb,Py‐
CuXn] were facilely prepared from commercially
readily available and cheap 3‐aminopropyltriethoxysilane
via immobilization on MCM‐41, followed by condensa-
tion with picolinaldehyde and then reaction with various
copper salts (Scheme 2). Firstly, 3‐aminopropyl‐functio-
nalized MCM‐41 [MCM‐41‐NH2] was obtained by
the condensation of mesoporous material MCM‐41 with
3‐aminopropyltriethoxysilane in toluene under reflux for
24 hr, followed by the silylation with Me3SiCl at room
temperature for 24 hr. The MCM‐41‐NH2 was subse-
quently reacted with picolinaldehyde in dry ethanol
under reflux for 24 hr to provide the Schiff base‐pyridine
bidentate ligand‐functionalized MCM‐41 [MCM‐41‐Sb,
Py]. The latter was then reacted with various copper salts
[CuXn = CuCl, CuBr, CuI, CuCl2, CuBr2, Cu (OAc)2, and
Cu (OTf)2] in DMF at room temperature for 7 hr to afford
the MCM‐41‐supported Schiff base‐pyridine bidentate
copper(I) or (II) complexes [MCM‐41‐Sb,Py‐CuXn] as pale
blue powders.
Figure 1 shows small angle X‐ray powder diffraction
(XRD) patterns of the parent MCM‐41, the MCM‐41‐Sb,
Py‐Cu (OAc)2 complex and the reused catalyst. The
diffraction pattern of the parent MCM‐41 exhibits an
intense peak at 2θ = 2.21° for d100 plane and also two
high order peaks with low intensity at 2θ = 3.80° and
4.36° for d110 and d200 planes respectively, which can be
attributed to hexagonally ordered mesoporous structure
of MCM‐41.[20a] The diffraction pattern of MCM‐41‐Sb,
Py‐Cu (OAc)2 was similar to that of MCM‐41, indicating
that the modified material MCM‐41‐Sb,Py‐Cu (OAc)2
contains ordered hexagonal arrays of one‐dimensional
channel structure. However, after introduction of the
copper complex, a significant decrease in the XRD peak
intensity was observed, which further confirmed that
grafting the copper complex occurs mainly inside
mesopore channels. These results indicate that the meso-
porous structure of MCM‐41 remains unaltered in the
Oxidative coupling has been developed into a highly
efficient, eco‐friendly and green method for the construc-
tion of carbon–carbon and carbon–heteroatom bonds.[14]
Transition‐metal‐catalyzed oxidative coupling reactions
have successfully been applied in organic synthesis owing
to the advantages of simplifying reaction steps, reducing
waste, and maximizing resource efficiency.[15] However,
stoichiometric amounts of oxidants such as copper salts,
PhI (OAc)2 and H2O2 are usually required. Reactions that
employ an internal oxidant are redox neutral, and no stoi-
chiometric external oxidants are needed; oxime is one
such internal oxidant.[16] Oxime acetates are readily
available materials and widely used in copper‐catalyzed
reactions for the construction of N‐heterocycles[17] and
some useful building blocks.[18] However, in all cases,
homogeneous copper catalysts with higher loadings (typ-
ically 5–20 mol%) were employed. Recycling of metal
catalysts is a task of great environmental and economic
significance in chemical and pharmaceutical industries.
Heterogeneous catalytic systems have several advan-
tages such as efficient site isolation and good dispersion
of their active sites, ease of separation of the product,
recyclability of the catalyst, better steric control of
the reaction intermediate and so on. In recent years, het-
erogeneous copper catalysts have been successfully
applied in various carbon–heteroatom bond formation
reactions.[19] However, to the best of our knowledge,
heterogeneous copper‐catalyzed oxidative coupling reac-
tion for the construction of C–S bond has not been
explored until now.
Nanosized mesoporous silica materials such as MCM‐
41 have recently emerged as smart and powerful supports
for immobilization of homogeneous catalysts because they
are advantageous over other solid supports in terms of
ultrahigh surface areas, big pore volumes, homogeneity
of the pores, and outstanding thermal stability.[20] To date,
Pd,[21] Rh,[22] Mo,[23] Au,[24] and Cu[25] complexes
anchored onto MCM‐41 have been employed in various
organic reactions as highly efficient and recyclable cata-
lysts. In continuation of our interest to develop green
and sustainable catalytic systems for organic transfor-
mations,21e–g, 24d, 25 herein we report the synthesis of an
MCM‐41‐supported Schiff base‐pyridine bidentate copper
(II) complex [MCM‐41‐Sb,Py‐ Cu (OAc)2] and its
SCHEME 1 Heterogeneous copper‐catalyzed synthesis of β‐keto
sulfones

XIA ET AL.
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SCHEME 2 Preparation of the MCM‐
41‐Sb,Py‐CuXn complexes
FIGURE 2 N2 adsorption/desorption isotherms of MCM‐41 and
MCM‐41‐Sb,Py‐Cu (OAc)2
FIGURE 1 XRD patterns of the parent MCM‐41 (a), MCM‐41‐Sb,
Py‐Cu (OAc)2 (b) and the reused catalyst (c)
whole process of catalyst preparation and the Cu complex
is well dispersed on the inner channel walls. The diffrac-
tion pattern of the reused catalyst was similar to that of
MCM‐41‐Sb,Py‐Cu (OAc)2, but the intensity of diffraction
peaks decreases further due to the presence of a trace
amount of products in inner channel.
and pore diameter decreased from 918 m2/g and 2.7 nm
to 587 m2/g and 2.2 nm, respectively. The energy disper-
sive spectroscopy (EDS) analysis performed with fresh
MCM‐41‐Sb,Py‐Cu (OAc)2 complex showed the presence
of Si, O, C, N, and Cu elements (Figure 4), also verifying
the successful grafting of the Sb,Py‐Cu (OAc)2 complex
onto MCM‐41.
FT‐IR spectra of MCM‐41, MCM‐41‐NH2, MCM‐41‐Sb,
Py, MCM‐41‐Sb,Py‐Cu (OAc)2 and the reused catalyst are
shown in Figure 5. The FT‐IR spectrum (Figure 5a) of
MCM‐41 shows the Si–O stretching absorption at 1084
and 801 cm−1. C–H and N–H vibration bands in the
3050–2800 cm−1 and 1630–1500 cm−1 regions were found
in the FT‐IR spectrum (Figure 5b) of MCM‐41‐NH2 and
these bands are surely absent in the case of MCM‐41. This
result shows that 3‐aminopropyltriethoxysilane has been
attached into the mesoporous silica matrix. The bands
observed at 1670 cm−1 and 1527 cm−1 for MCM‐41‐Sb,Py
(Figure 5c) could be attributed to the C=N and C=C
stretching frequency, respectively. In the FT‐IR spectrum
(Figure 5d) of MCM‐41‐Sb,Py‐Cu (OAc)2 absorptions at
2933 cm−1 (CH2), 1645 cm−1 (C=N) and 1524 cm−1
N2 adsorption–desorption isotherms for MCM‐41 and
MCM‐41‐Sb,Py‐Cu (OAc)2 are illustrated in Figure 2. As
expected, there are remarkable changes in the isotherms
before and after functionalization because the silylated
Schiff base‐pyridine bidentate copper (II) complex
entered the channels, but both samples gave similar
adsorption‐desorption isotherms of type IV (definition
by IUPAC),[23] demonstrating that the mesoporous struc-
ture of MCM‐41 was preserved. Figure 3 shows the BJH
pore size distributions for MCM‐41 and MCM‐41‐Sb,Py‐
Cu (OAc)2. The significant decreases in pore volume
and size were obviously observed for MCM‐41‐Sb,Py‐Cu
(OAc)2 due to the introduction of the silylated copper
(II) complex into the channels, but the pore still exhibited
a narrow distribution. After anchoring the Sb,Py‐Cu
(OAc)2 complex onto MCM‐41, the BET surface area

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XIA ET AL.
FIGURE 3 Pore size distributions of MCM‐41 and MCM‐41‐Sb,
Py‐Cu (OAc)2
FIGURE 5 FT‐IR spectra of MCM‐41 (a), MCM‐41‐NH2 (b),
MCM‐41‐Sb,Py (c), MCM‐41‐Sb,Py‐Cu (OAc)2 (d) and the reused
catalyst (e)
(C=C) were observed and the C=N stretching frequency
is red shifted by 25 cm−1, indicating the presence of
silylated Sb,Py‐Cu (OAc)2 complex. Finally, the FT‐IR
spectrum (Figure 5e) of the eighth reused catalyst was
similar to that of MCM‐41‐Sb,Py‐Cu (OAc)2, which show-
ing that the structure of the catalyst was maintained dur-
ing the reaction. Morphological changes of MCM‐41,
MCM‐41‐Sb,Py‐Cu (OAc)2 and the reused catalyst were
investigated by scanning electron microscopy (SEM). As
shown in Figure 6, the morphology of MCM‐41‐Sb,Py‐
Cu (OAc)2 (Figure 6b) is similar to the particle form of
MCM‐41 (Figure 6a), suggesting a high possibility in the
modification of copper complex on the inner channel of
MCM‐41 pores without any significant change in the
manner of MCM‐41. The morphology of the eighth
reused catalyst (Figure 6c) indicated that the ordered
mesostructure of the catalyst remained almost unaltered
after eight consecutive reaction cycles.
The 2D‐hexagonal arrangement of the pores with a differ-
ent contrast than that of the pore walls throughout the
specimen is quite clear. Hexagonal pore ordering after
the Schiff base‐pyridine bidentate ligand grafting and also
for Cu (II)‐binding with the composite has been observed.
It is further confirmed by the respective SAED (selected‐
area electron diffraction) pattern (Figure 7, inset) corrob-
orating with the hexagonal ordering of the pores. By
determination of the nitrogen content (C,H,N elemental
analysis), a Schiff base‐pyridine bidentate ligand loading
of approximately 1.06 mmol/g was calculated for MCM‐
41‐Sb,Py‐Cu (OAc)2.
Initially, the reaction of acetophenone oxime acetate
(1a) with sodium p‐toluenesulfinate (2a) was investigated
to determine the optimal reaction conditions, and the
results are listed in Table 1. First, the effect of various het-
erogeneous copper catalysts on the model reaction was
examined with toluene as solvent at 100 °C under Ar
(entries 1–7). All the copper catalysts tested could cata-
lyze the reaction to give the desired product 3a in 71–
High resolution transmission electron micrographs
(HRTEM) of MCM‐41‐Sb,Py‐Cu (OAc)2 are shown in
Figure 7 in the perpendicular direction of the pore axis.
FIGURE 4 EDS pattern of MCM‐41‐Sb,
Py‐Cu (OAc)2

XIA ET AL.
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FIGURE 6 SEM images of MCM‐41 (a), MCM‐41‐Sb,Py‐Cu (OAc)2 (b) and the reused catalyst (c)
the loading of the copper catalyst to 5 mol% resulted in a
decreased yield and required a longer reaction time (entry
14). Increasing the loading of the copper catalyst could
shorten reaction time, but did not increase the yield
(entry 15). When homogeneous Cu (OAc)2 was used as
catalyst, the desired 3a was isolated in 90% yield (entry
16), which indicating that the catalytic activity of MCM‐
41‐Sb,Py‐Cu (OAc)2 was comparable to that of Cu
(OAc)2. Therefore, the optimized catalytic system for this
transformation was the use of MCM‐41‐Sb,Py‐Cu (OAc)2
(10 mol%) with toluene as solvent at 100 °C under Ar
for 6 hr (entry 6).
With the optimized reaction conditions established, we
then explored the substrate diversity. Firstly, a wide vari-
ety of oxime acetates were examined and the results are
summarized in Table 2. As shown in Table 2, a wide
range of oxime acetates could undergo oxidative coupling
with sodium p‐tolylsulfinate 2a effectively and
subsequent hydrolysis to afford the corresponding β‐keto
sulfones in good to excellent yields. For example, various
para‐substituted acetophenone oxime acetates 1b‐1k
bearing either electron‐donating or electron‐withdrawing
groups could be converted into the desired products 3b‐
3k in 68–94% yields. Electron‐rich oxime acetates 1b‐1d
displayed a slightly higher reactivity than the electron‐
deficient ones 1e‐1k. meta‐Substituted acetophenone
oxime acetates 1l‐1o showed a similar reactivity with
the corresponding para‐substituted ones and gave the
expected β‐keto sulfones 3l‐3o in 74–90% yields. Notably,
FIGURE 7 TEM image of MCM‐41‐Sb,Py‐Cu (OAc)2
89% isolated yields. MCM‐41‐Sb,Py‐Cu (OAc)2 was found
to be the most efficient and afforded 3a in 89% yield
(entry 6). The reaction did not work without any copper
catalyst, which revealing special catalytic role of copper
in this transformation (entry 8). The effect of different
solvents on the reaction was also checked (entries 9–13).
When DMSO, DMF and 1,4‐dioxane were used as sol-
vents, the desired 3a could also be obtained in 70–81
yields, while DCE and MeCN afforded lower yields, so
toluene as solvent was the best choice (entry 6). Reducing

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XIA ET AL.
TABLE 1 Optimization of the reaction conditionsa
Entry
Copper catalyst
Solvent
Time (h)
Yield (%)b
1
MCM‐41‐Sb,Py‐CuCl
MCM‐41‐Sb,Py‐CuBr
MCM‐41‐Sb,Py‐CuI
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMSO
DMF
6
6
79
76
71
78
76
89
74
0
2
3
6
4
MCM‐41‐Sb,Py‐CuCl2
MCM‐41‐Sb,Py‐CuBr2
MCM‐41‐Sb,Py‐Cu (OAc)2
MCM‐41‐Sb,Py‐Cu (OTf)2
none
6
5
6
6
6
7
6
8
12
8
9
MCM‐41‐Sb,Py‐Cu (OAc)2
MCM‐41‐Sb,Py‐Cu (OAc)2
MCM‐41‐Sb,Py‐Cu (OAc)2
MCM‐41‐Sb,Py‐Cu (OAc)2
MCM‐41‐Sb,Py‐Cu (OAc)2
MCM‐41‐Sb,Py‐Cu (OAc)2
MCM‐41‐Sb,Py‐Cu (OAc)2
Cu (OAc)2
81
70
59
75
54
79
89
90
10
11
12
13
14c
15d
16
10
12
10
12
14
3
DCE
1,4‐dioxane
MeCN
toluene
toluene
toluene
6
aReaction was performed with 1a (0.5 mmol), 2a (0.5 mmol) and copper catalyst (10 mol%) in solvent (2 ml) at 100 °C under Ar, followed by stirring with silica
in CH2Cl2 at room temperature overnight.
bIsolated yield.
c5 mol% of MCM‐41‐Sb,Py‐Cu (OAc)2 was used.
d20 mol% of MCM‐41‐Sb,Py‐Cu (OAc)2 was used.
sterically hindered ortho‐substituted acetophenone oxime
acetates 1p and 1q also reacted well in this transformation,
thus giving the corresponding products 3p and 3q in 74%
and 92% yields, respectively. When 3′,4′‐dimethyl or
3′,4′‐dimethoxy‐substituted acetophenone oxime acetates
1r and 1s were used as substrates, the desired products 3r
and 3 s were obtained in high yields. In addition to
acetophenone oxime acetates, propiophenone oxime
acetates 1t‐1u and n‐butyrophenone oxime acetates
1v‐1w were also suitable substrates and afforded the corre-
sponding β‐keto sulfones 3t‐3w in 85–90% yields.
Heteroaryl substrates such as 1‐(thiophen‐2‐yl)ethanone
oxime acetate 1x could also provide the target product 3x
in 77% yield. Unfortunately, when alkyl oxime acetates,
1‐(pyridin‐2‐yl)ethanone oxime acetate or 1‐(pyridin‐3‐yl)
ethanone oxime acetate were employed as substrates, the
reaction did not occur at all.
sodium salts did not have a significant effect on this
transformation. When sodium benzenesulfinate 2b was
used as substrate, the desired β‐keto sulfone 3y was
obtained in 92% yield. The reactions of a variety of
para‐substituted sodium benzenesulfinates 2c‐2g with
1a also proceeded smoothly to give the corresponding
products 3z‐3d’ in 82–94% yields. These results indicate
that the electronic nature of the substituents on the aro-
matic ring of the sodium benzenesulfinate substrate has
limited influence on this heterogeneous copper‐catalyzed
oxidative coupling reaction. Various functional groups
such as fluoro, chloro, bromo, methoxy, and
trifluoromethyl were tolerated well. Sterically congested
sodium 2‐chlorobenzenesulfinate 2h and bulky sodium
2‐naphthalenesulfinate 2i proved to be suitable substrates
and gave the expected β‐keto sulfones 3e’ and 3f’ in good
yields. To our delight, the reaction also worked well with
aliphatic sulfinic acid sodium salts as substrates. For
instance, sodium methanesulfinate 2j and sodium
ethanesulfinate 2k could afford the corresponding prod-
ucts 3g’ and 3h’ in 95% and 84% yields, respectively.
Encouraged by the above results, the substrate scope of
sodium sulfinates was then explored with acetophenone
oxime acetate 1a as coupling partner and the results are
listed in Table 3. Generally, the nature of the sulfinic acid

XIA ET AL.
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TABLE 2 Substrate scope of various oxime acetatesa,b
aReaction was performed with 1 (0.5 mmol), 2a (0.5 mmol) and MCM‐41‐Sb,Py‐Cu (OAc)2 (10 mol%) in toluene (2 ml) at 100 °C under Ar for 6 hr, followed by
stirring with silica in CH2Cl2 at room temperature overnight.
bIsolated yield.
TABLE 3 Substrate scope of various sodium sulfinatesa,b
aReaction was performed with 1a (0.5 mmol), 2 (0.5 mmol) and MCM‐41‐Sb,Py‐Cu (OAc)2 (10 mol%) in toluene (2 ml) at 100 °C under Ar for 6 hr, followed by
stirring with silica in CH2Cl2 at room temperature overnight.
bIsolated yield.
The reactions of sodium ethanesulfinate 2k with 1d or 1s
also worked well, thus giving the desired products 3i’ and
3j’, respectively, in good yields. Unfortunately, when
electron‐deficient sodium trifluoromethanesulfinate or
sodium 3‐methoxy‐3‐oxopropane‐1‐sulfinate were used
as substrates, the reaction did not work.
To rule out the contribution of homogeneous cataly-
sis from more active soluble forms of copper, the

8 of 11
XIA ET AL.
no copper species had leached into the reaction solution.
Therefore, the actual catalytic activity should be attributed
to MCM‐41‐Sb,Py‐Cu (OAc)2 and not to the leached Cu
species in the solution.
A plausible mechanism for the heterogeneous copper‐
catalyzed oxidative coupling reaction between acetop-
henone oxime acetate 1a and sodium p‐toluenesulfinate
2a is shown in Scheme 3. First, MCM‐41‐Sb,Py‐Cu
(OAc)2 can be reduced to MCM‐41‐Sb,Py‐Cu(I)OAc by
2a.[18] Oxidative addition of the N–O bond of 1a to
MCM‐41‐Sb,Py‐Cu(I)OAc provides an MCM‐41‐bound
organo‐copper (III) intermediate A.[27] Subsequent coordi-
nation of 2a to intermediate A forms intermediate B along
with release of NaOAc. Then, intermediate D can be
produced after tautomerization of intermediate B to inter-
mediate C and subsequent activation of the vinyl C–H
bond by the Cu (III) species. Finally, reductive elimination
of intermediate D affords key intermediate E and regener-
ates MCM‐41‐Sb,Py‐Cu(I)OAc to complete the catalytic
cycle.[28] Intermediate E can be isolated in high yield
before hydrolysis to target product 3a.
From both an economical and an environmental point
of view, the recovery and recycle of the catalyst is a
major concern with a transition‐metal‐catalyzed organic
reaction for sustainability. The recyclability of MCM‐41‐
Sb,Py‐Cu (OAc)2 was then investigated in the reaction
of 4‐methylacetophenone oxime acetate 1b and sodium
p‐toluenesulfinate 2a and the results are shown in
Figure 9. Upon completion of the first reaction cycle,
the reaction mixture was diluted with ethyl acetate and
FIGURE 8 Plot of conversion versus time for the hot‐filtration
experiment
heterogeneity of MCM‐41‐Sb,Py‐Cu (OAc)2 was checked
by hot filtration.[26] For this, the oxidative coupling
reaction of acetophenone oxime acetate 1a with sodium
p‐toluenesulfinate 2a under the standard conditions was
conducted until an approximately 40% conversion of 1a.
The solid was then filtered off at 100 °C and the catalyst‐
free solution was stirred at 100 °C under Ar for 5 hr and
followed by GC. We found that after the removal of
MCM‐41‐Sb,Py‐Cu (OAc)2, the conversion of 1a stayed
around 40% during the period 2–7 hr (Figure 8). In con-
trast, if the catalyst was not filtered off, the conversion of
1a would reach 96% at 6 hr (Table 1, entry 6). Further-
more, analysis of the filtrate by ICP‐AES indicated that
SCHEME 3 Plausible mechanism for the formation of product 3

XIA ET AL.
9 of 11
purification. Oxime acetates were synthesized according
to the literature procedure.[17] All solvents were dried and
distilled before use. The products were purified by flash
chromatography on silica gel with light petroleum
ether/ethyl acetate as eluent. 1H NMR and 13C NMR spec-
tra were recorded on a Bruker Avance 400 (400 MHz) spec-
trometer with TMS as an internal standard in CDCl3 as
solvent. Melting points are uncorrected. Small angle XRD
measurements were performed with a SEIFERT‐FPM
XRD7 diffractometer with Cu Kα radiation at 40 kV and
36 mA. Copper content was determined with a Jarrell‐
Ash 1100 ICP analysis. N2 adsorption/desorption iso-
therms were obtained using a Bel Japan Inc. Belsorp‐HP
at 77 K. Prior to nitrogen adsorption measurements
samples were degassed at 423 K for 5 hr. X‐ray energy
dispersive spectroscopy (EDS) was performed using a
microscope. Mesoporous material MCM‐41 was prepared
according to literature method.[20a]
FIGURE 9 Recycle of the MCM‐41‐Sb,Py‐Cu (OAc)2 catalyst
filtered. The washing of the resulting solid with distilled
water and acetone followed by drying at 60 °C in vacuum
allowed the easy recovery of MCM‐41‐Sb,Py‐Cu (OAc)2.
As shown in Figure 9, the recovered MCM‐41‐Sb,Py‐Cu
(OAc)2 could be reused at least seven times with a slight
drop in the catalytic activity. Besides, the Cu content of
the recovered catalyst after the eighth reaction run was
determined to be 0.52 mmol g−1 by ICP‐AES analysis,
which indicating a negligible copper leaching.
4.1 | Preparation of MCM‐41‐Sb,Py
A mixture of 2.25 g of 3‐aminopropyltriethoxysilane and
2.81 g of the MCM‐41 in 160 ml of dry toluene was stirred
at 100 °C under Ar for 24 hr. The resulting solid was fil-
tered and washed by CHCl3 (30 ml), and dried under vac-
uum at 150 °C for 6 hr. Then the product was treated
with 5.0 g of Me3SiCl in 110 ml of dry toluene at 25 °C
with stirring for 24 hr. The solid product was filtered,
washed with acetone (3 × 30 ml) and dried under vacuum
at 110 °C for 6 hr. The dried white solid (1.71 g) was then
reacted with picolinaldehyde (0.251 g, 2.35 mmol) in
15 mL of dry ethanol at 80 °C for 24 hr. The product
was filtered, washed with ethanol (3 × 15 mL) and dried
under vacuum at 100 °C for 6 hr to give 1.756 g of hybrid
material MCM‐41‐Sb,Py. The nitrogen content was found
to be 2.38 mmol/g by elemental analysis.
3 | CONCLUSIONS
In conclusion, we have successfully developed a novel,
practical and environmentally friendly method for the
synthesis of β‐keto sulfones through heterogeneous
copper‐catalyzed oxidative coupling of oxime acetates
with sodium sulfinates, followed by hydrolysis. The pres-
ent method employs simple and readily available oxime
acetates and sodium sulfinates as starting materials and
has many attractive features, such as: (1) the substrate
scope is broad, and a variety of aryl (heteroaryl) oxime
acetates and aromatic or aliphatic sulfinic acid sodium
salts are allowed; (2) a wide variety of β‐keto sulfones
were obtained in good to excellent yields; (3) the reaction
needs no additional oxidants or additives because oxime
acetates serve not only as a substrate, but also as an oxi-
dant; (4) this new heterogeneous copper catalyst can eas-
ily be prepared by a simple procedure from readily
available and inexpensive reagents and recovered by fil-
tration of the reaction solution, and recycled up to eight
times with almost consistent activity.
4.2 | Preparation of MCM‐41‐Sb,Py‐Cu
(OAc)2
In a small Schlenk tube, 1.1 g of MCM‐41‐Sb,Py was
mixed with 0.127 g (0.7 mmol) of Cu (OAc)2 in 20 ml of
DMF. The resulting mixture was stirred at room temper-
ature for 7 hr under Ar. The product was filtered by
suction, washed with DMF (2 × 15 mL) and acetone
(2 × 15 ml) and dried at 70 °C under vacuum for 5 hr
to give 1.143 g of a pale blue copper complex [MCM‐41‐
Sb,Py‐Cu (OAc)2]. The nitrogen content was determined
to be 2.12 mmol/g by elemental analysis, and copper
content was found to be 0.53 mmol/g by ICP‐AES.
4 | EXPERIMENTAL
Unless otherwise stated, all reagents were purchased
from commercial suppliers and used without further
Other heterogeneous copper catalysts such as MCM‐41‐
Sb,Py‐CuCl, MCM‐41‐Sb,Py‐CuBr, MCM‐41‐Sb,Py‐CuI,

10 of 11
XIA ET AL.
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4.3 | General procedure for the
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To a 25 ml Schlenk tube were added MCM‐41‐Sb,Py‐Cu
(OAc)2 (95 mg, 0.05 mmol), oxime acetate 1 (0.5 mmol),
sodium sulfinate 2 (0.5 mmol), and toluene (2 ml). The
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After the reaction was completed (monitored by TLC),
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with 5 ml of EtOAc, and filtered. The MCM‐41‐Sb,Py‐Cu
(OAc)2 catalyst was washed with distilled water
(2 × 5 ml) and acetone (2 × 5 ml), dried in vacuum and
reused in the next run. The filtrate was quenched with
aqueous MgSO4 and the solvent was removed under vac-
uum. Then, the residue was stirred with silica gel in
CH2Cl2 at room temperature overnight. The resulting mix-
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ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of
China (No. 21462021) and Key Laboratory of Functional
Small Organic Molecule, Ministry of Education (No.
KLFS‐KF‐201704) for financial support.
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ORCID
Mingzhong Cai https://orcid.org/0000-0002-1056-2846
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
How to cite this article: Xia J, Huang X, You S,
Cai M. Heterogeneous copper‐catalyzed oxidative
coupling of oxime acetates with sodium sulfinates:
An efficient and practical synthesis of β‐keto
sulfones. Appl Organometal Chem. 2019;e5001.
https://doi.org/10.1002/aoc.5001
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