Copper-Catalyzed Aerobic Oxidative Cleavage of Unstrained Carbon-Carbon Bonds of 1,1-Disubstituted Alkenes with Sulfonyl Hydrazides

Article abstract of DOI:10.1002/cjoc.202000549

Alkoxy radical-mediated carbon-carbon bond cleavages have emerged as a powerful strategy to complement traditional ionic-type transformations. However, carbon-carbon cleavage reaction triggered by alkoxy radical intermediate derived from the combination of alkyl radical and dioxygen, is scarce and underdeveloped. Herein, we report alkoxy radical, which was generated from alkyl radical and dioxygen, mediated selective cleavage of unstrained carbon-carbon bond for the oxysulfonylation of 1,1-disubstituted alkenes, providing facile access to a variety of valuable β-keto sulfones. Mechanistic experiments indicated alkoxy radical intermediate that underwent subsequent regioselective β-scission might be involved in the reaction and preliminary computational studies were conducted to provide a detailed explanation on the regioselectivity of the C—C bond cleavage. Notably, the strategy was successfully applied for constructing uneasily obtained architecturally intriguing molecules.

Full text of DOI:10.1002/cjoc.202000549

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Copper-catalyzed aerobic oxidative cleavage of unstrained carbon-carbon
bonds of 1,1-disubstituted alkenes with sulfonyl hydrazides
Authors: Dong Yi,* Linying He, Zhongyu Qi, Zhijie Zhang, Mengshun Li, Ji Lu, Jun
Wei, Xi Du, Qiang Fu,* Siping Wei*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2020, 38, 10.1002/cjoc.202000549.
The final Version of Record (VoR) of it with formal page numbers will soon be
published online in Early View: http://dx.doi.org/10.1002/cjoc.202000549.
ISSN 1001-604X • CN 31-1547/O6
mc.manuscriptcentral.com/cjoc
www.cjc.wiley-vch.de

Chinese Journal
of Chemistry
Carbon-carbon cleavage, alkoxy radical, copper-catalyzed,
1,1-disubstituted alkenes, sulfonyl hydrazides
Report
CJC
中
国 化 学 - An International Journal
Copper-catalyzed aerobic oxidative cleavage of unstrained
carbon-carbon bonds of 1,1-disubstituted alkenes with sulfonyl
hydrazides
Dong Yi,*,a, # Linying He,a,b,# Zhongyu Qi,a Zhijie Zhang,a Mengshun Li,c Ji Lu,a Jun Wei,a Xi Du,a Qiang Fu,*,a Siping Wei*,a
a Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou 646000, China
b People’s Hospital of Xinjin District, Chengdu 611430, China
c School of Pharmacy, Binzhou Medical University, Yantai 264003, China
Cite this paper: Chin. J. Chem. 2019, 37, XXX—XXX. DOI: 10.1002/cjoc.201900XXX
Summary of main observation and conclusion Alkoxy radical-mediated carbon-carbon bond cleavages have emerged as a powerful strategy to
complement traditional ionic-type transformations. However, carbon-carbon cleavage reaction triggered by alkoxy radical intermediate derived from the
combination of alkyl radical and dioxygen, is scarce and underdeveloped. Herein, we report alkoxy radical, which was generated from alkyl radical and
dioxygen, mediated selective cleavage of unstrained carbon-carbon bond for the oxysulfonylation of 1,1-disubstituted alkenes, providing facile access to a
variety of valuable β-keto sulfones. Mechanistic experiments indicated alkoxy radical intermediate that underwent subsequent regioselective β-scission
might be involved in the reaction and preliminary computational studies were conducted to provide a detailed explanation on the regioselectivity of the
C-C bond cleavage. Notably, the strategy was successfully applied for constructing uneasily obtained architecturally intriguing molecules.
strategy for selective C-C bond cleavage and building highly
valuable compounds. While our manuscript was under
preparation, an example of the combination of hydrogen atom
transfer (HAT) with alkoxyl radical, derived from alkyl radical
Background and Originality Content
Catalytic and selective cleavage of carbon-carbon bonds,
which would provide a complementarily powerful strategy to
organic
transformation,
remains
less
explored
and
capturing dioxygen, for the diverse functionalization of C-C bond
adjacent to arene was reported by Liu’s group (Scheme 1b)[7].
β-Ketosulfones are widely applied in the synthesis of natural
products, pharmaceuticals and agrochemicals and exhibit
interesting biological properties,[8] great efforts have hence been
devoted for the synthesis of the compounds with various
sulfonylating agents.[9] In particular, a variety of methods based on
the oxysulfonylation of alkenes with sulfonylhydrazides have been
developed to access β-ketosulfones. For example, Wang’s[8a]
group has proposed copper-catalyzed synthesis of β-ketosulfones
starting from alkenes with oxygen. Alternatively, Zhang’s group
has reported metal-free aerobic oxidative synthesis of
underdeveloped in organic chemistry due to the difficulties
associated with discriminating the carbon-hydrogen and
carbon-carbon bonds and thermodynamically stability of C-C σ
bond in organic molecules.[1] In order to conquer the above
challenges, the well-developed C-C bond cleavage reactions
usually depend on specific substrates bearing strained rings,
chelation-assisted groups or electron-withdrawing groups to
polarize the C-C bonds.[2] Thus, the development of a general and
more efficient strategy for selective C-C bond cleavage remains
highly desirable. With the rapid development of radical chemistry,
a wide range of reactions involving selective C-C bond cleavage by
a radical process has emerged as an interesting strategy for the
preparation of value-added compounds.[3] In particular, great
progress has been achieved in alkoxy radical initiated β-scission
for the ring-opening functionalization of cycloalkanols to furnish
more valuable products (Scheme 1a). For example, transition
metal-catalyzed[4] or photocatalytic[5] alkoxy radical-mediated
ring-opening functionalization of cycloalkanols has made great
achievements. In those works, the key alkoxy radical
intermediates generate from the hydroxyl groups of the
substrates. The direct use of dioxygen as oxygen source for
constructing hydroxyl or carbonyl groups in oxygen-containing
organic frameworks has been achieved via radical processes in the
past several years.[6] We wondered whether alkoxy radical, which
has been applied in the selective C-C bond cleavage, could be
generated from the reaction between alkyl radical and dioxygen.
The realization of the hypothesis could provide a powerful
β-ketosulfones[8d]
.
Recently, visible-light-promoted aerobic
oxidative difunctionalization of alkenes for the construction of
β-ketosulfones has been disclosed by Wang and Zhu’s groups.[10]
Despite the above achievements, there is still a great demand for
the development of alternative strategies to access β-ketosulfones
in synthetic chemistry. 1,1-Disubstituted alkenes served as
powerful building blocks in organic synthesis.[11] However, as a
result of the challenges associated with the selective C-C bond
cleavage of unstrained C-C bonds of 1,1-disubstituted alkenes,
oxysulfonylation of 1,1-disubstituted alkenes with oxygen
affording corresponding β-ketosulfones has not yet been
described in literature. Inspired by the alkoxy radical-mediated C-C
cleavage, herein, we report copper-catalyzed aerobic oxidative
carbon-carbon cleavage of simple unstrained 1,1-disubstituted
alkenes without the assistance of directing group for constructing
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.202000549
This article is protected by copyright. All rights reserved.

First author et al.
Report
β-ketosulfones via O-centered alkoxy radical in situ generated
Table 1 Optimization of the reaction conditions.a
from alkyl radical and oxygen (Scheme 1c).
O
Catalyst
+
Ts
TsNHNH2
Ph
oC)
Ph
Ph
T
Solvent,
(
Scheme 1 Alkoxy radical-mediated regioselective C-C bond cleavage via
β-scission
1a
2a
3aa
O
2 (balloon)
Entry
1
Catalyst
Solvent
3aa (%)b
30c
52
ref. and
Alkoxyl radical derived from
4
5)
group
(a)
hydroxyl
(
CuI
CuI
MeCN/H2O (5:1)
MeCN/H2O (5:1)
MeCN/H2O (5:1)
MeCN/H2O (5:1)
MeCN/H2O (5:1)
MeCN/H2O (5:1)
THF/H2O (5:1)
OH
O
O
O
or
TM
hv
X
Y
X
(sp3)C
2
n
n
n
n
3
Cu2O
CuBr2
46
atom transfer combined with alkoxy radical
from dioxygen
FG
generated
(b) Hydrogen
work, ref.
Liu's
7
O
4
55
n
n
Ar
Ar
5
Cu(OAc)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
―
79
H
N3
HN3
6
86
7
44
O
O2
-scission
β
n
8
DME/H2O (5:1)
DMSO/H2O (5:1)
NMP/H2O (5:1)
MeCN/H2O (3:1)
MeCN/H2O (7:1)
MeCN/H2O (9:1)
MeCN/H2O (11:1)
MeCN
76
n
Ar
Ar
Ar
O
work:
9
This
Radical addition combined with alkoxy radical
from dioxygen
58
generated
(c)
10
11
12
13
14
15
16
17
18
19
20
33
O
O
O
S
cat.
Cu
X
+
R3SO2NHNH2
Ar
Ar
R3
O2
51
R1 R2
89
•
R3SO2
X
R1
R2
-scission
β
93
92
X
R1
R2
O
S
O
O
X
O2
51
O
S
O
R1
R3
R3
54d
46e
31f
0g
Ar
R2
MeCN/H2O (9:1)
MeCN/H2O (9:1)
MeCN/H2O (9:1)
MeCN/H2O (9:1)
MeCN/H2O (9:1)
Ar
26h
Results and Discussion
a Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), Catalyst (5 mol %),
Solvent (2 mL), 65 °C, 12 h, O2 (balloon). Isolated yield based on 1a.
Catalyst (2 mol %), 40 °C, 7 h. d 50 °C. e 80 °C. f Air (balloon). g N2 (balloon). h
24 h.
Our studies commenced with α-benzylstyene 1a and
p-toluenesulfonyl hydrazide 2a as the model substrates using
cuprous iodide (CuI) as catalyst under O2 atmosphere, and
acetonitrile loaded with some water was used as the solvent, in
which water was employed to increase the solubility of compound
2a. To our delight, the selective carbon-carbon bond cleavage of
substrate 2a was observed, affording the desired product 3aa in
30% yield (Table 1, entry 1). After screening of the catalysts, it was
found that Cu(OTf)2 was the ideal catalyst, leading to the desired
product in 86% yield while other copper salts gave lower yields
(entries 2-6). Then, different solvents, such as THF, DME, DMSO,
and NMP loaded with water were examined, acetonitrile was still
the best choice (entries 7-10). After the solvent screening, the
impact of the amount of water on the reaction was investigated, it
was found that when MeCN/H2O (9:1, V/V) was used as the
solvent, the optimal 93% yield was obtained (entries 11-15). Next,
no better yield was obtained when the reaction temperature was
decreased or increased (entries 16 and 17). Finally, control
experiments revealed that oxygen or copper catalyst was crucial
to the success of the reaction (entries 18-20).
b
c
With the optimal conditions in hand (Table 1, entry 13), we
subsequently evaluated the generality of the radical-induced C-C
cleavage reaction for oxysulfonylation of different kinds of
1,1-disubstituted alkenes. As illustrated in Table 2, a diverse array
of styrenes bearing different groups at α-position could undergo
C-C bond cleavage with high selectivity. The substrates with
different functional groups at para-, meta- and ortho-position of
benzyls, including methyl (1a), methoxyl (1b, 1h, and 1j), halogens
(1c-1e, 1i and 1k), trifluoromethyl (1f), all reacted well. We next
turned our attention to examine the compatibility of substrates
with various functional groups attached to the α-carbon atom.
Pleasingly, a broad range of functional groups had no significant
effect on the radical-induced C-C bond cleavage process. As also
shown in Table 2, various heteroatom-containing functional
groups, such as hydroxyl (1n), methoxyl (1o), phenoxyl (1p),
acyloxyl (1q), sulfonyloxyl (1r), amino (1s-1v), azido (1w),
phosphonyl (1x) and sulfonyl (1y), are tolerated well, affording the
desired product via C-C bond cleavage in 42-73% yields,
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
demonstrating the flexibility of the current method. Notably,
moderate yields could also be obtained with styrenes bearing
tertiary-carbon (1z and 1aa). In addition, C(sp2)-C(sp2) bond
resided in 1,1-diphenyl-ethylene 1ab could also be selectively
cleaved albeit in relatively lower yield, which might be attributed
to different reactivity of substrate 1ab and higher bond energy of
C(sp2)-C(sp2) bond than C(sp2)-C(sp3) bond in the alkoxy radical
intermediate. Additionally, the substrate 1ac containing C-C triple
bond was also compatible in the reaction. Taken together, the
selectivity of the carbon-carbon cleavage could be controlled in a
selective manner by substituents on the alkenes. Besides, a
gram-scale model reaction was carried out to afford the product
3aa in 63% isolated yield, demonstrating the practicality and
Having demonstrated the powerful capability of the method
in the radical-initiated carbon-carbon bond cleavage of diverse
1,1-disubstituted alkenes, the scope of the substitutes on the
arenes was investigated. As illustrated in Table 3, the substrates
bearing electron-donating (3ba, 3da-3ea) or electron-withdrawing
(3ha-3ja) groups at the para-position of phenyls all underwent the
reaction smoothly. The substrates with methoxyl (3ka and 3ma) or
fluoride (3la and 3na) substituted at meta- or ortho-position could
also afford the desired products via selective C-C cleavage.
Substrates containing naphthyl (3oa) or furyl (3pa) could also be
applied to the transformation. Furthermore, the generality of the
method with respect to the sulfonyl hydrazide coupling partner
was explored using α-benzylstrene 1a as the substrate. Aryl
scalability of the present method (see SI for more details). Notably, sulfonyl hydrazides containing methoxyl (3ab), halogen (3ac-3ae,
X, leaving as a substituted carbon radical, might transform into
oxygenated products with oxygen, coupling products with another
radical, or some unidentified products after the reaction.
3la, and 3na), cyano (3ia), trifluoromethyl (3ag) or nitro (3ah)
substituents were compatible. Additionally, 2-naphthyl, 3-pyridyl
and 2-thienyl sulfonyl hydrazides (3ak-3am) reacted under the
optimized conditions to afford the products in moderate yields.
Finally, alkyl sulfonyl hydrazide (3an) could also undergo
high-yielding coupling with the model substrate 1a, which was
possibly due to the fact that alkyl sulfonyl hydrazide could be
more easily oxidized to alkyl radical but also alkyl sulfonyl radical
was more reactive than aryl sulfonyl radical.
Table 2 Substrate scope of 1,1-disubstituted alkenes.a,b
O
2 (balloon)
mol
O
%)
Cu(OTf)2 (5
+
Ts
X
TsNHNH2
Ph
Ph
H
MeCN/H O
V/V)
(9:1,
2
R
1a
Me;
1 R2
65 o 12 h
C,
2a
3aa
R1 R2
,
Leaving
=
or
=
X
group
OMe
R
Ph
Ph
1l
Ph
R
Ph
R2
R
R2
,
=
63%
H,
=
=
=
=
=
=
OMe 60% 1j
R
,
,
1a
1h
=
OMe 75%
,
R
R
R
R
R
Me
63%c
R
,
, 93%,
,
R2 Me 58%
=
1m
=
, ,
1b
1c
1i
=
R
Cl 66%
,
1k
R
,
OMe 61%
,
,
,
Cl 65%
,
Br 83%
,
,
1d
Cl 78%
,
,
,
OH
OCH3
OPh
1e
1f
77%
F
,
Ph
1n
Ph
Ph
Ph
=
R
CF3 66%
,
,
1o
1s
1p
,
70%
62%
59%
,
,
=
1g
R
COOMe 51%
,
,
OBz
OTs
NiPr2
44%
NHPh
Ph
Ph
Ph
1q
1r
1t
64%
42%
,
,
,
,
65%
O
O
Ph)2
N3
N
N(SO2
P(OEt)2
Ph
Ph
1w
Ph
Ph
O
1u
1v
1x
70%
73%
70%
72%
,
,
,
,
,
Ph
Ph
Ts
Ph
Ph
1y
Ph
Ph
62%d
76%
28%e
,
1z
1aa
1ab
59%
,
,
O
Ph
1ac 44%
,
a 1 (0.5 mmol), 2 (1.0 mmol), Cu(OTf)2 (5 mol %), MeCN/H2O (9:1, 2 mL),
65 °C, 12 h, O2 (balloon). b Isolated yields based on 1. c Performed at 6
c
mmol scale of 1a. When R1, R2, X = H, β-hydroxysulfone was obtained in
d
e
66%.
Ring-opening products were identified by LC-HRMS.
Two
byproducts acetophenone and (2-tosylethene-1,1-diyl)dibenzene were
isolated and confirmed by NMR spectra.
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

First author et al.
Report
Table 3 Substrate scope of α-benzyl substituted styrenes and sulfonyl
E selectivity[14]. The success of these experiments indicate that the
protocol could constitute a potentially useful strategy for further
functionalization of the commodity chemicals.
hydrazides.a,b
O
2 (balloon)
mol
O
O
S
O
%)
Cu(OTf)2 (5
Scheme 2 Synthetic applications of the reaction.
R1SO2NHNH2
+
Ph
O
Ar
R1
Ar
MeCN/H O
V/V)
(9:1,
2
and
in structurally
C=C double bond
C-C
single
bond cleavage
(a)
complex
molecules
65 o 12 h
1
2
3
C,
O
O
2 (balloon)
R
O
O
Ts
SO2R1
5
R
Ts
Ts
R1
SO2
NHNH
Ts
equiv)
2 (2
R
R
Ph
MeCN/H O
,
Cu(OTf)2
2
R
O
•
65 oC 12 h
4ac-af
1ac-af
,
=
=
3ka R
Me
3ma R
Me
70%
,
O
73%
O
=
,
,
,
3ba R Me
62%
80%
,
,
=
=
,
3la R
,
F
3na R F 41%
35%
=
,
,
3ca R Ph
,
,
O
O
O
S
5
O
O
=
=
3da R
Me
,
O
79%
81%
,
Me
Ts
5
Me
Ts
5
O
3ea R
Ph
,
O
O
,
R2
Ts
=
Ts
3fa R Br
48%
,
,
CF3
=
=
R
Cl 63%
,
,
R2 4-H, 4ac 52%
3ga
3ha R
4af 27%
,
=
,
4ae
30%
,
O
F
40%
,
,
R2 4-Cl 4ad 38%
=
,
,
3oa
81%
38%
,
3pa
,
=
3ia R
CN 37%
,
,
=
Product transformations
R
COOMe 39%
,
,
3ja
(b)
O
Ts
OH
Ph
ref.
12
O
O
O
O
S
O
O
O
S
O
S
O
Ph
Ph
Br
Ph
Ph
Ph
Ph
Ph
O
Ts
6
60%
,
R
Br
=
3ab R
Me
83%
,
O
,
Ph
K
2CO3,
Br
acetone
3ai
3aj
61%
O
59%
,
,
substitution
Nucleophilic
=
3ac R Br
69%
,
,
O
=
3ad R
Cl 64%
,
,
O
O
KBr, H O AcOH
O
,
O
NaBH4
THF-MeOH
a)
2
2
OH
O
S
=
3ae R F 41%
,
,
S
10%
NaOH
aq.
b)
Br
Ts
86%
Ts
Ts
Ph
Ph
=
3af R
,
CN 70%
,
Ph
5
Ph
Reduction
Debenzoylation
N
7
,
=
3aa
64%
,
3ag R
CF3 81%
,
,
=
3ah R NO2 42%
3ak
,
3al
59%
O
43%
,
,
,
p-MeO-C6 4COCH2
H
Br
Desulfonylation
K2CO3 DMF
,
O
O
O
S
O
O
O
S
E
Ph
p-MeO-C6H4
Ph
S
O
3am
3an
85%
,
61%
,
8
79%
,
a 1 (0.5 mmol), 2 (1.0 mmol), Cu(OTf)2 (5 mol %), MeCN/H2O (9:1, 2 mL),
65 °C, 12 h, O2 (balloon). b Isolated yields based on 1.
A final set of studies focused on the detailed mechanism of
the reaction. As shown in Scheme 3, the model reaction was
completely suppressed when radical scavenger
To validate the potential applicability of the strategy, aryl
substituted cyclohexenes 1ac-af were subjected to the standard
reaction conditions, and they could undergo carbon-carbon
cleavage smoothly to furnish structurally interesting products 4
ac-af (Scheme 2a). Particularly, an intriguing C=C double bond
cleavage occurred in the reaction which could be hardly achieved
by other methods. Then, the utility of the method was further
confirmed by facile derivatization of the product 3aa (Scheme 2).
For example, the keto group of the product could be easily
reduced to generate β-hydroxysulfone 5. Intermolecular
nucleophilic substitution between β-ketone sulfone and cinnamyl
bromide provided the mono-C-cinnamylation product 6, which
could be stereoselectively transformed into sulfonyl
tetrahydropyrans via sequential reduction, epoxidation, and
ring-closure[12]. Moreover, α-bromomethyl sulfone 7 could also be
achieved in moderate yield via mono-bromination and
base-induced chemoselective cleavage.[13] Furthermore, the
combination of the β-keto sulfone with α-bromo ketone formed
an extremely valuable unsymmetric 1,4-enedione 8 with complete
2,2,6,6-tetramethyl-piperidinyloxyl (TEMPO) or butylated
hydroxytoluene (BHT) was added into the reaction system
(Scheme 3a), indicating that a radical process might be involved in
the present cleavage reaction. Subsequently, isotope-labeling
experiments were performed under 18O2 or in H218O to get a more
in-depth understanding of the pivotal role of dioxygen in the
transformation. When the model reaction was conducted under
18O2 atmosphere, 62% of 18O-labeled product 3aa was detected in
HR-MS spectra (Scheme 3b, and see SI). Upon performing the
reaction in the presence of H218O, 36% of 18O-labeled product 3aa
was detected in HR-MS spectra (Scheme 3c, and see SI). And,
when the model reaction was conducted under both 18O-labeled
H218O and 18O2, 89% of 18O-labeled product 3aa was detected.
Moreover, oxygen exchange between the product 16O-3aa and
H218O via the hydrate was observed by the oxygen scrambling
experiment under the standard conditions (Scheme 3d, and see
SI).[8a] The combination of the above results provided strong
support for the carbonyl oxygen originating from dioxygen.
Besides, when substrate 3aa′ was subjected to the standard
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
reactions, no corresponding product was detected, precluding the
possibility that 3aa′ was the key intermediate in the reaction
(Scheme 3e). Furthermore, when 3aa′ was transformed into
alkoxy radical-mediated by cerium photocatalysis,[5f] the product
3aa was obtained smoothly, providing the evidence that an alkoxy
radical mediated β-scission process might be involved in the
reaction (Scheme 3f).
oxygen atom of carbonyl group of 3aa could undergo reversible
oxygen atom exchange with water. In addition, benzaldehyde
hydrazone J, compound K, TEMPO-trapped compounds D' and G'
were detected through LC-HRMS analysis of the ongoing reaction
mixture, which validates the existence of radicals D and G,
providing further evidence for the reaction mechanism.
Importantly, preliminary computational studies indicated that the
C-C bond cleavage of position a of alkoxy radical F was more
thermodynamically favorable than β-scission of position b and c
due to the much lower energetic barrier of the transition state
(See SI for more information).
Scheme 3 Mechanistic studies.
O
2 (balloon)
O
MeCN/H O
,
Cu(OTf)2
2
+
Ts
TsNHNH2
Ph
(a)
Ph
Ph
TEMPO
equiv)
equiv)
(2.0
(2.0
or
BHT
3aa trace
2a
,
1a
65 o 12 h
C,
Scheme 4 Possible reaction mechanism.
18
O
2 (balloon)
O2
O2
O
MeCN/H O
,
Cu(OTf)2
2
+
+
+
Ts
TsNHNH2
Ph
Ph
Ph
Ph
Ph
65 o 12 h
2CuII
+
2H
(b)
(c)
+
+
CuII
O2
+
C,
2CuI
CuI
H
Ph
Ts
18O-3aa:16O-3aa 62:38
=
2a
1a
1a
fast
Ph
TsN=NH
Ts
TsNHNH2
TsN=N
slow
2HOO
1a
O2
(balloon)
N2
2O2
HOO
2a
A
B
C
O
18O
2
H
MeCN/
,
Cu(OTf)2
65 o 12 h
Ts
TsNHNH2
a
Ph
CuI CuII
Ph
Ph
Ph
b
C,
-scission
β
HOO
O
18O-3aa:16O-3aa 36:64
=
2a
HOO
Ph
O
Ts
Ts
Ts
Ph
Ph
Ph
c
18O2
(balloon)
Ph
G
D
E
F
3aa
O
18O
O2
H
MeCN/
,
HAT
Cu(OTf)2
2
Ph
Ts
TsNHNH2
Ph
Ts
Ph
Ph
Ph
65 o 12 h
C,
(d)
(e)
OO
Ph
C
O2
Ts
18O-3aa:16O-3aa 89:11
1a
2a
=
D-O
CuI
2a
O2
Ts
(balloon)
OO
O
PhCH=NNH
J
Ts
PhCHO
O
Ph
Ph
18O
H
MeCN/
,
Cu(OTf)2
65 o 12 h
2
Ts
K
I
H
II-OH]
Ph
[Cu
C,
LC-HRMS
LC-HRMS
16O-3aa
18O-3aa:16O-3aa 53:47
=
+H+
+H+
K
247.0787
] (m/z):
found: 247.0788
J
275.0849
[
[
] (m/z):
found: 275.0833
O2
(balloon)
Ph
O
OH
H
2O
MeCN/
,
atom exchange of
O
3aa with H
Cu(OTf)2
65 o 12 h
2O
HO O*H
Ts
Oxygen
Ts
Ts
Ts
Ph
Ph
Ph
(f)
O*
H2O*
C,
+
′
′
H2O
none
3aa
,
3aa
Ts
Ts
N
Ph
3aa-Hydrate
Ph
Ph
Ph
CeCl
mol%)
3 (2
TBACl mol%)
Ph
3aa
3aa*
Boc
N
O
OH
(5
Ph
Boc
Ts
87%
+
N
Ph
3aa
(g)
H
DBAD
(1.5 equiv),
Blue LEDs
MeCN
Ph
3aa
,
LC-HRMS
O
N
r.t., 12 h
(30 W),
O
[M+Na]+
:
345.1785
Ts
Ph
LC-HRMS
found: 345.1782
D'
G'
LC-HRMS
,
,
G+TEMPO+H+
248.2009
+
D
+TEMPO+H
506.2723
[
] (m/z):
found: 506.2728
[
] (m/z):
found: 248.1998
Based on the above observations, LC-HRMS analysis (see SI for
more information) and previous reports[6b, 8a], a plausible
mechanism for the present transformation is described in Scheme
4. Initially, a sulfonyl radical would be formed from sulfonyl
hydrazide 2a via intermediate A and B with the release of N2. The
sulfonyl radical would attack the double bond of alkene 1a to
provide the alkyl radical intermediate D, which captures an O2 to
deliver peroxide radical intermediate D-O. Subsequently, the
intermediate D-O might undergo hydrogen atom transfer (HAT)
giving rise to intermediate E. Also, intermediate E might be
formed through the coupling between alkyl radical intermediated
D with peroxyl radical (OOH) generated form oxygen. Then, the
single electron transfer (SET) between intermediate E and Cu(I)
results in alkoxy radical F. Eventually, highly selective β-scission of
the carbon-carbon of the intermediate F would lead to the final
product 3aa along with the benzyl radical G,[15] which could react
with oxygen or sulfonyl radical C leading to the corresponding
aldehyde I and radical-radical coupling molecule K. Notably, the
Conclusions
In summary, we have successfully developed an aerobic
copper-catalyzed radical-initiated selective cleavage of unstrained
carbon-carbon bond for the oxysulfonylation of 1,1-disubstituted
alkenes. The protocol features excellent chemo- and
regio-selectivities, good functional group tolerance, broad
substrate scope, high yields and could be readily extended to
reconstruct structurally complex molecules. Notably, the alkoxy
radicals involved in the reaction are generated from alkyl radicals
and dioxygen. We anticipate that the present protocol would be
beneficial to the development of alkoxy radical-mediated
regioselective carbon-carbon bond cleavage with dioxygen for the
construction of structurally more complex products that are
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

First author et al.
Report
difficult to access by other approaches. Further studies on the
nature of alkoxy radical are undergoing in our laboratory.
Pathway. Angew. Chem. Int. Ed. 2012, 51, 12570-12574. (b) Liu,
Z.-Q.; Zhao, L.; Shang, X.; Cui, Z. Unexpected Copper-Catalyzed
Aerobic Oxidative Cleavage of C(Sp3)–C(Sp3) Bond of Glycol Ethers.
Org. Lett. 2012, 14, 3218-3221. (c) Chen, Y.; Lu, L.-Q.; Yu, D.-G.;
Zhu, C.-J.; Xiao, W.-J. Visible Light-Driven Organic Photochemical
Synthesis in China. Sci. China Chem. 2019, 62, 24-57. (d) Morcillo,
S. P. Radical-Promoted C−C Bond Cleavage: A Deconstructive
Approach for Selective Functionalization. Angew. Chem. Int. Ed.
2019, 58, 14044-14054. (e) Sivaguru, P.; Wang, Z.; Zanoni, G.; Bi, X.
Cleavage of Carbon–Carbon Bonds by Radical Reactions. Chem.
Soc. Rev. 2019, 48, 2615-2656. (f) Smaligo, A. J.; Swain, M.;
Quintana, J. C.; Tan, M. F.; Kim, D. A.; Kwon, O.
Hydrodealkenylative C(Sp3)–C(Sp2) Bond Fragmentation. Science
2019, 364, 681-685. (g) Wang, P.-Z.; He, B.-Q.; Cheng, Y.; Chen,
J.-R.; Xiao, W.-J. Radical C–C Bond Cleavage/Addition Cascade of
Benzyl Cycloketone Oxime Ethers Enabled by Photogenerated
Cyclic Iminyl Radicals. Org. Lett. 2019, 21, 6924-6929. (h) Wang, Y.;
Yang, L.; Liu, S.; Huang, L.; Liu, Z.-Q. Surgical Cleavage of
Unstrained C(Sp3)−C(Sp3) Bonds in General Alcohols for
Heteroaryl C−H Alkylation and Acylation. Adv. Synth. Catal. 2019,
361, 4568-4574. (i) Wu, X.; Zhu, C. Recent Advances in Alkoxy
Radical-Promoted C–C and C–H Bond Functionalization Starting
from Free Alcohols. Chem. Commun. 2019, 55, 9747-9756. (j)
Zhang, G.; Liu, Y.; Zhao, J.; Li, Y.; Zhang, Q. Radical Cascade
Reactions of Unsaturated C-C Bonds Involving Migration. Sci.
China Chem. 2019, 62, 1476-1491.
Experimental
Cu(OTf)2 (9 mg, 5 mol%) was added to a mixture of
1,1-disubstituted alkene 1 (0.5 mmol), sulfonyl hydrazide 2 (1.0
mmol), and MeCN/H2O (2 mL, 9/1) in a 25 mL round-bottomed
flask at room temperature under O2 (balloon). The reaction vessel
was allowed to stir at 65 °C for 12 h. Upon completion of the
reaction, the resulting mixture was concentrated under vacuum
and the residue was purified by flash column chromatography
using petroleum ether/ethyl acetate (v/v 10:1 to 1:1) to provide
the desired product.
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
Acknowledgement
We are grateful for the financial support from the
Collaborative Fund of Luzhou Government and Southwest Medical
University
(2019LZXNYDJ28,
2018LZXNYD-ZK33,
2018LZXNYD-ZK39), and the research fund of Southwest Medical
University (2017-ZRZD-020 and 2017-ZRQN-031).
References
[4] (a) Wang, Y.-F.; Chiba, S. Mn(Iii)-Mediated Reactions of
Cyclopropanols with Vinyl Azides: Synthesis of Pyridine and
2-Azabicyclo[3.3.1]Non-2-En-1-Ol Derivatives. J. Am. Chem. Soc.
2009, 131, 12570-12572. (b) Ilangovan, A.; Saravanakumar, S.;
Malayappasamy, S. Γ-Carbonyl Quinones: Radical Strategy for the
Synthesis of Evelynin and Its Analogues by C–H Activation of
Quinones Using Cyclopropanols. Org. Lett. 2013, 15, 4968-4971. (c)
Ren, R.; Zhao, H.; Huan, L.; Zhu, C. Manganese-Catalyzed Oxidative
Azidation of Cyclobutanols: Regiospecific Synthesis of Alkyl Azides
by CC Bond Cleavage. Angew. Chem. Int. Ed. 2015, 54,
12692-12696. (d) Zhao, H.; Fan, X.; Yu, J.; Zhu, C. Silver-Catalyzed
Ring-Opening Strategy for the Synthesis of Β- and Γ-Fluorinated
Ketones. J. Am. Chem. Soc. 2015, 137, 3490-3493. (e) Lu, S.-C.; Li,
H.-S.; Xu, S.; Duan, G.-Y. Silver-Catalyzed C2-Selective Direct
Alkylation of Heteroarenes with Tertiary Cycloalkanols. Org.
Biomol. Chem. 2017, 15, 324-327. (f) Allen, B. D. W.; Hareram, M.
D.; Seastram, A. C.; McBride, T.; Wirth, T.; Browne, D. L.; Morrill, L.
[1] (a) Liu, H.; Feng, M.; Jiang, X. Unstrained CarbonCarbon Bond
Cleavage. Chem. Asian J. 2014, 9, 3360-3389. (b) Marek, I.;
Masarwa, A.; Delaye, P.-O.; Leibeling, M. Selective Carbon–Carbon
Bond Cleavage for the Stereoselective Synthesis of Acyclic Systems.
Angew. Chem. Int. Ed. 2015, 54, 414-429. (c) Morioka, T.;
Nishizawa, A.; Furukawa, T.; Tobisu, M.; Chatani, N.
Nickel-Mediated Decarbonylation of Simple Unstrained Ketones
through the Cleavage of Carbon–Carbon Bonds. J. Am. Chem. Soc.
2017, 139, 1416-1419.
[2] (a) Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chelation-Assisted
Carbon–Hydrogen and Carbon–Carbon Bond Activation by
Transition Metal Catalysts. Chem. Eur. J. 2002, 8, 2422-2428. (b)
Chen, F.; Wang, T.; Jiao, N. Recent Advances in
Transition-Metal-Catalyzed Functionalization of Unstrained
Carbon–Carbon Bonds. Chem. Rev. 2014, 114, 8613-8661. (c) To, C.
T.; Chan, K. S. Selective Aliphatic Carbon–Carbon Bond Activation
by Rhodium Porphyrin Complexes. Acc. Chem. Res. 2017, 50,
1702-1711. (d) Jia, K.; Chen, Y. Visible-Light-Induced Alkoxyl
C.
Manganese-Catalyzed
Electrochemical
Deconstructive
Chlorination of Cycloalkanols Via Alkoxy Radicals. Org. Lett. 2019,
21, 9241-9246.
[5] (a) Bloom, S.; Bume, D. D.; Pitts, C. R.; Lectka, T. Site-Selective
Approach to Β-Fluorination: Photocatalyzed Ring Opening of
Cyclopropanols. Chem. Eur. J. 2015, 21, 8060-8063. (b) Guo, J.-J.;
Hu, A.; Chen, Y.; Sun, J.; Tang, H.; Zuo, Z. Photocatalytic C−C Bond
Radical
Generation
for
Inert
Chemical
Bond
Cleavage/Functionalization. Chem. Commun. 2018, 54,
6105-6112.
[3] (a) Liu, H.; Dong, C.; Zhang, Z.; Wu, P.; Jiang, X.
Transition-Metal-Free Aerobic Oxidative Cleavage of C-C Bonds in
Α-Hydroxy Ketones and Mechanistic Insight to the Reaction
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
Cleavage and Amination of Cycloalkanols by Cerium(Iii) Chloride
Complex. Angew. Chem. Int. Ed. 2016, 55, 15319-15322. (c) Jia, K.;
Zhang, F.; Huang, H.; Chen, Y. Visible-Light-Induced Alkoxyl Radical
Generation Enables Selective C(Sp3)–C(Sp3) Bond Cleavage and
Functionalizations. J. Am. Chem. Soc. 2016, 138, 1514-1517. (d)
Ren, R.; Wu, Z.; Xu, Y.; Zhu, C. C−C Bond-Forming Strategy by
Manganese-Catalyzed Oxidative Ring-Opening Cyanation and
Ethynylation of Cyclobutanol Derivatives. Angew. Chem. Int. Ed.
2016, 55, 2866-2869. (e) Yayla, H. G.; Wang, H.; Tarantino, K. T.;
Orbe, H. S.; Knowles, R. R. Catalytic Ring-Opening of Cyclic
Alcohols Enabled by Pcet Activation of Strong O–H Bonds. J. Am.
Chem. Soc. 2016, 138, 10794-10797. (f) Jia, K.; Pan, Y.; Chen, Y.
Selective Carbonyl−C(Sp3) Bond Cleavage to Construct Ynamides,
Ynoates, and Ynones by Photoredox Catalysis. Angew. Chem. Int.
Ed. 2017, 56, 2478-2481. (g) Hu, A.; Chen, Y.; Guo, J.-J.; Yu, N.; An,
Q.; Zuo, Z. Cerium-Catalyzed Formal Cycloaddition of
Cycloalkanols with Alkenes through Dual Photoexcitation. J. Am.
Chem. Soc. 2018, 140, 13580-13585. (h) Chen, Y.; Du, J.; Zuo, Z.
Selective C-C Bond Scission of Ketones Via Visible-Light-Mediated
Cerium Catalysis. Chem 2019, 6, 266-279. (i) Gazi, S.; Đokić, M.;
Chin, K. F.; Ng, P. R.; Soo, H. S. Visible Light–Driven Cascade
Carbon–Carbon Bond Scission for Organic Transformations and
Plastics Recycling. Adv. Sci. 2019, DOI: 10.1002/advs.201902020,
10.1002/advs.201902020. (j) Ota, E.; Wang, H.; Frye, N. L.;
Liu, C.; Lu, Q.; Huang, Z.; Zhang, J.; Liao, F.; Peng, P.; Lei, A. Nmp
and O2 as Radical Initiator: Trifluoromethylation of Alkenes to
Tertiary Β-Trifluoromethyl Alcohols at Room Temperature. Org.
Lett. 2015, 17, 6034-6037. (f) Wang, H.; Lu, Q.; Qian, C.; Liu, C.; Liu,
W.; Chen, K.; Lei, A. Solvent-Enabled Radical Selectivities:
Controlled Syntheses of Sulfoxides and Sulfides. Angew. Chem. Int.
Ed. 2016, 55, 1094-1097. (g) Xu, X.; Li, B.; Zhao, Y.; Song, Q.
Aerobic Oxidative Decyanation–Amidation of Arylacetonitriles
with Urea as a Nitrogen Source. Org. Chem. Front. 2017, 4,
331-334.
[7] Wang, Y.; Wang, N.; Zhao, J.; Sun, M.; You, H.; Fang, F.; Liu, Z.-Q.
Visible-Light-Promoted Site-Specific and Diverse Functionalization
of a C(Sp3)–C(Sp3) Bond Adjacent to an Arene. ACS Catal. 2020,
10, 6603-6612.
[8] (a) Wei, W.; Liu, C.; Yang, D.; Wen, J.; You, J.; Suo, Y.; Wang, H.
Copper-Catalyzed Direct Oxysulfonylation of Alkenes with
Dioxygen and Sulfonylhydrazides Leading to Β-Ketosulfones. Chem.
Commun. 2013, 49, 10239-10241. (b) Wang, H.; Wang, G.; Lu, Q.;
Chiang, C.-W.; Peng, P.; Zhou, J.; Lei, A. Catalyst-Free
Difunctionalization of Activated Alkenes in Water: Efficient
Synthesis of Β-Keto Sulfides and Sulfones. Chem. Eur. J. 2016, 22,
14489-14493. (c) Yang, D.; Huang, B.; Wei, W.; Li, J.; Lin, G.; Liu, Y.;
Ding, J.; Sun, P.; Wang, H. Visible-Light Initiated Direct
Oxysulfonylation of Alkenes with Sulfinic Acids Leading to
Β-Ketosulfones. Green Chem. 2016, 18, 5630-5634. (d) Wan, X.;
Sun, K.; Zhang, G. Metal-Free Tetra-N-Butylammonium
Knowles, R. R.
A
Redox Strategy for Light-Driven,
out-of-Equilibrium Isomerizations and Application to Catalytic C–C
Bond Cleavage Reactions. J. Am. Chem. Soc. 2019, 141, 1457-1462. Bromide-Mediated Aerobic Oxidative Synthesis of Β-Ketosulfones
(k) Shi, J.-L.; Wang, Z.; Zhang, R.; Wang, Y.; Wang, J.
Visible-Light-Promoted Ring-Opening Alkynylation, Alkenylation,
and Allylation of Cyclic Hemiacetals through Β-Scission of Alkoxy
from Styrenes. Sci. China Chem. 2017, 60, 353-357. (e) Liu, Q.; Liu,
F.; Yue, H.; Zhao, X.; Li, J.; Wei, W. Photocatalyst-Free Visible
Light-Induced Synthesis of Β-Oxo Sulfones Via Oxysulfonylation of
Radicals. Chem. Eur. J. 2019, 25, 8992-8995. (l) Wang, Y.; Liu, Y.; He, Alkenes with Arylazo Sulfones and Dioxygen in Air. Adv. Synth.
J.; Zhang, Y. Redox-Neutral Photocatalytic Strategy for Selective C–
Catal. 2019, 361, 5277-5282.
C Bond Cleavage of Lignin and Lignin Models Via Pcet Process. Sci.
[9] (a) Lu, Q.; Zhang, J.; Zhao, G.; Qi, Y.; Wang, H.; Lei, A.
Bull. 2019, 64, 1658-1666. (m) Zhao, K.; Yamashita, K.; Carpenter, J. Dioxygen-Triggered Oxidative Radical Reaction: Direct Aerobic
E.; Sherwood, T. C.; Ewing, W. R.; Cheng, P. T. W.; Knowles, R. R.
Catalytic Ring Expansions of Cyclic Alcohols Enabled by
Proton-Coupled Electron Transfer. J. Am. Chem. Soc. 2019, 141,
8752-8757.
Difunctionalization of Terminal Alkynes toward Β-Keto Sulfones. J.
Am. Chem. Soc. 2013, 135, 11481-11484. (b) Handa, S.;
Fennewald, J. C.; Lipshutz, B. H. Aerobic Oxidation in Nanomicelles
of Aryl Alkynes, in Water at Room Temperature. Angew. Chem. Int.
Ed. 2014, 53, 3432-3435. (c) Tang, X.; Huang, L.; Xu, Y.; Yang, J.; Wu,
W.; Jiang, H. Copper-Catalyzed Coupling of Oxime Acetates with
Sodium Sulfinates: An Efficient Synthesis of Sulfone Derivatives.
Angew. Chem. Int. Ed. 2014, 53, 4205-4208. (d) Liu, Q.; Liu, F.; Yue,
H.; Zhao, X.; Li, J.; Wei, W. Photocatalyst-Free Visible Light-Induced
Synthesis of Β-Oxo Sulfones Via Oxysulfonylation of Alkenes with
Arylazo Sulfones and Dioxygen in Air. Adv. Synth. Catal. 2019, 361,
5277-5282.
[6] (a) Wei, W.; Ji, J.-X. Catalytic and Direct Oxyphosphorylation of
Alkenes with Dioxygen and H-Phosphonates Leading to
Β-Ketophosphonates. Angew. Chem. Int. Ed. 2011, 50, 9097-9099.
(b) Lu, Q.; Zhang, J.; Wei, F.; Qi, Y.; Wang, H.; Liu, Z.; Lei, A. Aerobic
Oxysulfonylation of Alkenes Leading to Secondary and Tertiary
Β-Hydroxysulfones. Angew. Chem. Int. Ed. 2013, 52, 7156-7159. (c)
Su, Y.; Sun, X.; Wu, G.; Jiao, N. Catalyst-Controlled Highly Selective
Coupling and Oxygenation of Olefins: A Direct Approach to
Alcohols, Ketones, and Diketones. Angew. Chem. Int. Ed. 2013, 52,
9808-9812. (d) Tang, C.; Jiao, N. Copper-Catalyzed Aerobic
Oxidative C—C Bond Cleavage for C—N Bond Formation: From
[10] (a) Wu, J.; Zhang, Y.; Gong, X.; Meng, Y.; Zhu, C. Visible-Light
Promoted Aerobic Difunctionalization of Alkenes with Sulfonyl
Hydrazides for the Synthesis of Β-Keto/Hydroxyl Sulfones. Org.
Ketones to Amides. Angew. Chem. Int. Ed. 2014, 53, 6528-6532. (e) Biomol. Chem. 2019, 17, 3507-3513. (b) Wen, J.; Yang, X.; Sun, Z.;
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

First author et al.
Report
Yang, J.; Han, P.; Liu, Q.; Dong, H.; Gu, M.; Huang, L.; Wang, H.
Biomimetic Photocatalytic Sulfonation of Alkenes to Access
Β-Ketosulfones with Single-Atom Iron Site. Green Chem. 2020, 20,
230-237.
[14] Li, S.-Y.; Wang, X.-B.; Jiang, N.; Kong, L.-Y. Synthesis of
(E)-1,4-Enediones from Α-Halo Ketones through a Sodium
Sulfinate Mediated Reaction. Eur. J. Org. Chem. 2014, 2014,
8035-8039.
[11] Li, X.; Xu, X.; Zhou, C. Tetrabutylammonium Iodide Catalyzed
Allylic Sulfonylation of Α-Methyl Styrene Derivatives with
Sulfonylhydrazides. Chem. Commun. 2012, 48, 12240-12242.
[12] Chang, M.-Y.; Lu, Y.-J.; Cheng, Y.-C. M-Cpba-Mediated
Stereoselective Synthesis of Sulfonyl Tetrahydropyrans.
Tetrahedron 2015, 71, 1192-1201.
[13] Suryakiran, N.; Prabhakar, P.; Srikanth Reddy, T.; Chinni
Mahesh, K.; Rajesh, K.; Venkateswarlu, Y. Chemoselective Mono
Halogenation of Β-Keto-Sulfones Using Potassium Halide and
Hydrogen Peroxide; Synthesis of Halomethyl Sulfones and
Dihalomethyl Sulfones. Tetrahedron Lett. 2007, 48, 877-881.
[15] Bietti, M.; Gente, G.; Salamone, M. Structural Effects on the
Β-Scission Reaction of Tertiary Arylcarbinyloxyl Radicals. The Role
of Α-Cyclopropyl and Α-Cyclobutyl Groups. J. Org. Chem. 2005, 70,
6820-6826.
(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
Version of record online: XXXX, 2019
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
Entry for the Table of Contents
Page No.
R1
R2
O O
Copper-catalyzed aerobic oxidative cleavage of
unstrained
1,1-disubstituted
hydrazides
O
O
O
O
R2
[Cu]
O2
+
R3SO2NHNH2
S
carbon-carbon
alkenes
bonds
with sulfonyl
of
S
R3
Ar
Ar
examples, up
R3
Ar
R1
57
to 93%
alkoxy radical
yield
•
•
•
Reconstruction of
Alkoxy radical intermediate
from dioxygen
molecules
organic
generated
O
Selective C-C bond cleavage
Ts
Ph
Ph
Dong Yi,*,a,# Linying He,a,b,# Zhongyu
Qi,a Zhijie Zhang,a Mengshun Li,c Ji Lu,a
Jun Wei,a Xi Du,a Qiang Fu,*,a Siping
Wei*,a
Herein, we report alkoxy radical, which was generated from alkyl radical and dioxygen, mediated
selective cleavage of unstrained carbon-carbon bond for the oxysulfonylation of 1,1-disubstituted
alkenes, providing facile access to a variety of valuable β-keto sulfones. Importantly, the strategy
was successfully applied for constructing uneasily obtained architecturally intriguing molecules.
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.