Catalytic [3+3] Annulation of β-Ketoethers and Cyclopropenones via C(sp3)—O/C—C Bond Cleavage under Transition-Metal Free Conditions

Article abstract of DOI:10.1002/cjoc.202100276

The efficient cleavage of carbon-oxygen (C—O) bond is highly important for the transformation of oxygen-rich biomass and industry chemicals. Herein, an efficient [3+3] annulation of β-ketoethers with cyclopropenones in the presence of catalytic base has b

Full text of DOI:10.1002/cjoc.202100276

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Catalytic [3+3] Annulation of β-Ketoethers and Cyclopropenones via C(sp3)-
O/C-C Bond Cleavage Under Transition-metal Free Conditions
Authors: Dachang Bai, abJunyan Chen, Bingbing Zheng, Xueyan Li, and Junbiao
Chang *
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2021, 39, 10.1002/cjoc.202100276.
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.202100276.
ISSN 1001-604X • CN 31-1547/O6
mc.manuscriptcentral.com/cjoc
www.cjc.wiley-vch.de

For submission: https://mc.manuscriptcentral.com/cjoc
Report
CJC
For published articles: https://onlinelibrary.wiley.com/journal/16147065
中
国 化 学 - An International Journal
Cite this paper: Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Catalytic [3+3] Annulation of β-Ketoethers and Cyclopropenones
via C(sp3)-O/C-C Bond Cleavage Under Transition-metal Free Con-
ditions
Dachang Bai, *,abJunyan Chen,a Bingbing Zheng,a Xueyan Li,a and Junbiao Chang *,a
a NMPA Key Laboratory for Research and Evaluation of Innovative Drug, Collaborative Innovation Center of Henan Province for Green
Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007 (China)
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai
200032, P R China
Keywords
C-O/C-C activation | [3+3] annulation |β-ketoethers | cyclopropenones | transition-metal free conditions
Main observation and conclusion
The efficient cleavage of carbon-oxygen (C-O) bond is highly important for the transformation of oxygen-rich biomass and industry
chemicals. Herein, an efficient [3+3] annulation of β-ketoethers with cyclopropenones in presence of catalytic base has been devel-
oped, which proceed through the C(sp3)-O bonds cleavage in β-ketoethers and C-C bond cleavage in cyclopropenones under transi-
tion-metal free conditions. The cleavage of C(sp3)-O bonds in alkyl alkyl ethers and aryl alkyl ethers were realized. The reaction fea-
tured excellent functional group compatibility and chemoselectivity, affording various 2-pyrones in good to excellent yields under
mild conditions and simple operation.
Comprehensive Graphic Content
O
R3
cat. tBuOK
R2 Me
=
O
O
R3
Ar
Ar
Transition
Metal
O
O
R1
O
R2
O
Ar
+
R3
R3
R1
R3
R3
O
cat. tBuOK
R2
+
R3
R2 Ar
O
=
R3
R1
•
•
•
•
•
annulation
reaction Transition-metal
condition
free
C-C/C-O bond cleavage
[3+3]
•
scope
Broad substrate
Excellent chemoselectivity Mild reaction condition
*E-mail: baidachang@htu.edu.cn;changjunbiao@zzu.edu.cn
View HTML Article
Supporting Information
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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.202100276
This article is protected by copyright. All rights reserved.

First author et al.
Report
enolization. The mixture of geometric isomers may complicate the
annulation process; 2) The C-O bonds in the β-ketoethers are
highly insert, which may lead to low efficiency; 3) The protonation
of the reaction intermediate can be a competitive reaction after
the ring-opening of cyclopropenone.
Background and Originality Content
The ubiquity of C-O bond in nature has stimulated efforts to-
wards their efficient transformation to afford diverse organic plat-
forms.1 Although the direct conversion of C-O bonds of esters,
carbonates, carbamates and sulfates are studied very well, the
cleavage of C-O bonds in inexpensive ethers is more challenge
because of its low polarity and reactivity.2 In the past several dec-
ades, many efforts have been developed for the chemical conver-
sion of the C-O bonds in ethers into value-added chemicals.3
Among these investigations, the cleavage of sp2 C-O bonds in aryl
aryl ethers, aryl alkyl ethers and sp3 C-O bonds in aryl alkyl ethers,
benzyl alkyl ethers or benzyl allyl ethers have been the main fo-
cus,1-3 while the sp3 C-O bonds activation in other alkyl alkyl ethers
are rarely reported. In this regard, the C-O cleavage in β-ketoethers
has attracted great attention, as the keto aryl alkyl ethers are of-
ten utilized as the model compounds to disclose the chemical
transformation of lignin.4 Some representative approaches have
been reported to convert the lignin model compounds (keto aryl
alkyl ethers) using nickel catalysts, ruthenium complexes, vanadi-
um complexes and so on.5 These strategies usually require harsh
conditions or transition-metal-based catalysis. Only some transi-
tion-metal catalysis free routes for the C-O bond cleavage in keto
aryl ethers were developed in recent years,6-9 through ionic liquid
inducing oxidation process or classic Baeyer-Villiger oxidation re-
action with stoichiometric oxidant reagent (Scheme 1a).8
Results and Discussion
We initiated set out to explore the possibility of C(sp3)-O cleav-
age in β-ketoethers by investigating the coupling of commerical
available material 1a with diphenylcyclopropenone 2a (Table 1).
When the reaction was performed in MeOtBu at 30℃ for 12h, the
[3+3] annulation product 3a was not observed using the base of
CH3COOK, K2CO3, NEt3 or DBU (Table 1, entries 1-4), only CH3ONa
gave the product 3a in 13% yield (Table 1, entry 5). To our delight,
t
when BuOK was used, the cyclic product 3a could be obtained in
93% yield (Table 1, entry 6). The yield decreased slightly when the
reaction performed under the air atmosphere (Table 1, entry 7),
and higher temperature resulted slight lower yield as the decom-
position of cyclopropenone 2a (Table 1, entry 8). Screening of the
solvent revealed that the yield of 3a could be isolated in 98%
when DME was used as the solvent (Table 1, entry 9). The reaction
in dioxane, THF and toluene as well as polar solvent such as EtOH,
DMA also resulted in good to excellent yields of 3a (Table 1, en-
tries 10-15), while no desired product observed when
1,2-dichloroethane (DCE) was used as solvent (Table 1, entry 16).
Furthermore, only starting materials 1a and 2a were recovered in
the absence of tBuOK (Table 1, entry 17)
Scheme 1 Selected examples of C-O cleavage of β-ketoethers and C-C
cleavage of cyclopropenones in absence of transition-metal catalysis.
Table 1 Optimization of Reaction Conditions.
C-O cleavage of -ketoethers under transition-metal free conditions
β
(a)
O
O
O
Ionic
liquids
Baeyer-
Villiger
O
O
O
+
Ar
O
O
Ph
Ph
+
Base
O
ROH
R'
R
O
+
O
Ar
R
Ar
O
Ar
OH
OMe
Oxidation
Oxidation
solvent
R'
Ph
R'
=
=
Ar
R
Ar
R
Ph
Ph
Ph
1a
2a
3a
work)
via C-C cleavage
(Lin's
annulation of -ketoesters with
β
(b) [3+2]
cyclopropenones
O
O
O
o
Ar
mol
Entry
Base
Solvent
T
Yield
(%)
%)
DBU
(10
( C)
+
EWG
O
R
Ar
EWG
Ar
Ar
MeOtBu
MeOtBu
MeOtBu
MeOtBu
MeOtBu
MeOtBu
MeOtBu
MeOtBu
DME
30
30
30
30
30
30
30
60
30
30
30
30
30
30
30
30
30
NR
R
=
or
EWG CO2R', CN Bz
1
2
CH3COOK
K2CO3
NR
NR
NR
13
93
80
85
98
85
90
82
85
74
86
NR
NR
3
annulation of -ketoethers with
via
O
cleavage
β
(c) [3+3]
O
cyclopranones
C(sp )-O/C-C
3
N(Et)3
DBU
4
R2OH
R2 Me
O
=
R1
cat. t
BuOK
OR2
O
+
or
5
CH3ONa
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
--
+
Ar
-
O
OR2
R1
R1
R1
Ar
6
R3
R2
R1
O
=
R2 Ar
R3
7b
8c
9
R1
On the other hand, the cyclopropenones have been utilized as
important building skeletons with transition-metal or or-
gano-catalysis via C-C bond cleavage process,10 which could server
as 3C synthon in the [3+n] annulation reaction with various cou-
pling partners.11 Recently, Lin group reported the [3+2] annulation
of cyclopropenones with β-ketoesters under base conditions, the
electron-withdrawing group in the ketoester is crucial to the reac-
tion transformation(Scheme 1b).11c Herein, we report the [3+3]
annulation of β-ketoethers with cyclopropenones via C(sp3)-O/C-C
bond fission in presence of catalytic potassium t-butoxide without
the using of transition-metal catalysis, affording various 2-pyrones
in good to excellent yields with excellent chemoselectivity
10
11
12
13
14
15
16
17
dioxane
THF
toluene
PhCF3
EtOH
DMA
DCE
MeOtBu
a
mmol)
in
solvent
1a
2a
Reaction conditions:
mmol),
mmol), base
(0.2
b Under the air. c 60 oC.
(0.2
(0.02
12
30 o
h,
C, argon.
(2.0 mL),
(Scheme 1c). 2-pyrones constitute the key structural units of nu-
The scope and generality of this [3+3] annulation reaction was
evaluated with the optimized conditions (Scheme 2). First, the
compatibility of β-ketoethers was investigated. The β-ketoethers
bearing methyl-, methoxyl-, fluoro-, chloro- groups at the pa-
ra-position of the benzene ring were all tolerated, giving the de-
sired products in high to excellent yield (3a-3e, 75-99% yield). The
reaction also worked smoothly in the presence of methyl-,
methyoxyl-, fluoro- and chloro- groups at the meta-position of the
12
merous natural products and pharmaceuticals.
This general,
mild and clean method for cleavage of sp3 C-O bonds of the alkyl
alkyl ethers were furthermore expand to lignin models β-O-4 link-
age (keto aryl alkyl ethers) for synthetic transformations. Com-
pared to other C-O bond activations, there are three issues to
overcome: 1) The oxygen or carbon atom of keto group could both
be nucleophilic site after the deprotonation (α-position) as the
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
benzene ring (3f-3i, 90-99% yield). The cyclic products with ortho-
methyl (3j) or methoxyl group (3k) at the benzene ring were ob-
tained in 99% yield and 98% yield respectively. The presence of
phenyl group at the α-position of the β-ketoether afforded the
tetra-phenyl-substituted 2-pyrone 3l in 74% yield. The β-ketoether
with a methyl group at the α-position resulted in decreased reac-
2-pyrone 3z in 99% yield and ester 5a in 58% yield (Table 2, entry
6).
Table 2 Scope of lignin model compounds.
O
O
O
O
Ph
Ph
t
O
u
r
+
KO B
OA
+
tivity
(3m,
34%
yield).
The
coupling
of
r
O
A
Ph
Ph
DME
Ph
1-cyclohexyl-2-methoxyethan-1-one 2n with diphenylcycloprope-
none 2a failed to give the cyclic product. Further exploration
demonstrated the scope of cyclopropenones in this reaction sys-
R2
Ph
Ph
Ph
R2
a
2
4
3
5
t
n r
E
t y
e one
K
t
ro uc
d
ro uc
P
d
t 5
4
t 3
P
tem. Diphenylcyclopropenone bearing methyl-, Bu-, fluoro- and
chloro- groups at the C4-position of the benzene ring underwent
smooth transformation, and the desired annulation products
3o-3r were isolated in 71-89% yields. Several other cycloprope-
nones were also briefly examined, affording the desired products
3s-3u in 53-99% yields. The dialkyl- substituted cyclopropenones
could proceed very well (3v, 95% yield). Meanwhile, this coupling
system can be extended to the nonsymmetrical cyclopropenones
with excellent regioselectivity (3w, 47% yield and 3x, 93% yield).
Low yield of 3w as the decomposition of cyclopropenone. The
cyclopronones containing heterocyclic ring such as thiophene
could be converted to the desired product 3y in 99% yield.
O
O
O
Ph
Ph
1a
2a
3a
O
Ph
OPh
O
Ph
Ph
O
Ph
Ph
,
,
a
4
a
a
5
e
e
3
99% yi ld
83% yi ld
e
O
OM
O
O
Ph
Ph
O
O
Ph
Ph
e
Ph
,
O
M
Ph
,
,
a
3
e
e
6% yi ld
4b
5b
7
99% yi ld
O
e
COM
O
O
O
Ph
Ph
O
Ph
O
e
M
Ph
CO
Ph
Ph
,
c
4
a
3
c
e
e
5
99% yi ld
98% yi ld
O
O
O
Scheme 2 Substrates Scope.
Ph
Ph
O
OPh
4b
Ph
O
Ph
Ph
O
Ph
e
M
Ph
O
O
O
e
M
R3
R4
KOtBu
DME
OMe
,
m
,
+
O
a
e
e
4d
3
5
7
99% yi ld
O
2% yi ld
R1
R3
R4
R2
R1
e
OM
O
Ph
Ph
R2
3
O
O
5b
1
2
Ph
Ph
O
ketone variations
(A)
e
M
Ph
e
O
M
Ph
,
O
R
R
H
yield
99%
yield
98%
99%
75%
96%
e
O
M
3f Me
Ph
Ph
3a
,
e
4
m
3
e
e
%
yi ld
O
Ph
Ph
7
1
%
yi ld
5b
7
2
3g
3h
3i
OMe 99%
F
Cl 90%
3b Me
O
O
98%
3c
3d
3e
OMe
F
Cl 90%
O
Ph
Ph
O
O
OPh
R
6a
Ph
O
Ph
R
O
Ph
O
O
O
r
B
O
O
Ph
Ph
r
Ph
Ph
Ph
B
O
R
Ph
Ph
O
,
,
z
3
a
e
e
4f
5
99% yi ld
58% yi ld
Ph
Ph
Ph
.
.
.
.
a
,
,
,
,
36 h
t
a
2
mm
mm
u
mm
,
n
i
m
l
)
eac on con ons:
o
l
o
o
t
R
ti
diti
0 2
4
(
0 1
l
)
KO B 0 01
l
DME 1 0
(
(
)
(
)
Ph
Me
.
.
.
.
,
,
4
yield
50 o
C
m
g
R
80 o
ti
diti
0 2
(
l
)
0 1
(
l
KO B 0 01
b
R
ar on eac on con ons:
a
mmo
mmo
u
mmo
n
l i DME
)
2
)
(
,
.
.
,
ar on
g
b
,
,
3j Me
<
5%
99%
3l 74%
,
3n
3m
34%
yield
yield
yield
1
(
l
)
h
0
36
C
3k
OMe 98%
variations
(B) cyclopronones
R
R
R
Then we briefly explored the reaction mechanism (Scheme 3).
No corresponding product was observed when
O
O
O
R
R
yield
79%
yield
86%
3o Me
3p tBu 71%
3s Me
O
3t
Cl 99%
2,2-dimethyl-1-phenylpropan-1-one 1z reacted with cycloprope-
none 2a even at higher temperature (Scheme 3, eq. 1), and this
result demonstrated that the enol intermediate under base condi-
tion is crucial for the reaction conversion. Moreover, the H/D ex-
change reaction was performed, when CD3OD was added into the
coupling system of 1a with 2a, H/D exchanged was observed at
the 5-position of the product 3a with partial deuteration (73% D),
indicating that protonation of the enolization intermediate oc-
coured before the ring-opening of cyclopropenone and not likely
involved in the turnover-limiting step (Scheme 3, eq. 2).
3q
3r
F
72%
Ph
Ph
Ph
Cl 89%
R
Cl
Cl
S
S
O
O
O
O
R1 R2
3v nPr nPr
yield
95%
R1
O
O
3w Ph Me 47%
3x Ph
93%
R2
Ph
cyclo-
propyl
Cl
Cl
Cl
3u
3y
53%
99%
,
,
yield
yield
a
mmol),
mmol), KOtBu
in DME
mL) 36 h
mmol)
mmol)
and
1
2
Reaction conditions:
,
,
(0.2
(0.2
(0.2
(0.02
mmol),
(2.0
30 o
C
Reaction conditions:
mL) 36 h 30 o
C
, , ,
argon.
mmol),
KO Bu
in
b
t
1
2
(0.1
,
argon.
(0.1
DME
(1.0
Scheme 3 Mechanism studies.
We then turned our attention to the transformation of β-O-4
linkage 4 (keto aryl alkyl ether) which were used as the lignin
model compounds. The present base conditions allowed the direct
conversion of the lignin model 4a to 2-pyrone 3a in 99% yield
along with formation of phenyl (E)-2,3-diphenylacrylate 5a in 83%
yield just using two equiv cyclopropenone 2a at slightly higher
temperature (Table 2, entry 1). Installation of the methoxyl- or
acetyl- group on the benzene ring resulted in excellent conversion
(Table 2, entries 2 and 3). It is worthy of note that the presence of
methyl group at α-position in the β-ketoethers allowed direct
conversion of lignin model 4d and 4e to corresponding products in
moderate to excellent yields (Table 2, entries 4 and 5). The bro-
mo-substituted compound 4f gave corresponding products
O
O
tBuOK
mol%)
(10
+
1)
OMe
NR
O
(eq.
°
Ph
DME, 30 C
Ph
Ph
1z
2a
Ph
Ph
O
tBuOK
mol%)
O
O
(10
CD OD
+
2)
(eq.
OMe
(10.0 eq),
DME
Ph
3
Ph
Ph
Ph
H/D
73%
D
-
Dn 3a 89%
1a
2a
,
yield
On the base of our mechanism experiments results and previ-
ous related reports,10, 14 proposed mechanistic possibilities of this
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

First author et al.
Report
[3+3] annulation is shown in Scheme 4. Deprotonation of
β-ketoether 4a by tBuOK generated the enol intermediate A and B,
the in-situ formed nucleophilic oxygen anion attacks the carbonyl
group of cyclopropenone 2a gave intermediate C, subsequently
ring-opening process and intramolecular cyclization reaction de-
livered the anion species D. Finally, the β-O elimination process
gave the final product 3a and regenerated the base.
(2020T130176 and 2020M682306). We also thank the financial
support from Henan Key Laboratory of Organic Functional Mole-
cules and Drug Innovation.
References
(a) Zhang, T. Taking on all of the biomass for conversion. Science 2020,
367, 1305-1306; (b) Wu, L.P.; Moteki, T.; Gokhale, A.A.; Flaherty, D.W.;
Toste, F.D. Production of Fuels and Chemicals from Biomass: Condensa-
tion Reactions and Beyond. Chem 2016, 1: 32-58; (c) Corma, A.; Iborra, S.;
Velty, A. Chemical routes for the transformation of biomass into chemi-
cals. Chem. Rev. 2007, 107, 2411-2502; (d) Huber, G.W.; Iborra, S.; Corma,
A. Synthesis of transportation fuels from biomass: Chemistry, catalysts,
and engineering. Chem. Rev. 2006, 106: 4044-4098.
Scheme 4 Proposed Reaction Mechanism.
MeOH
O
tBuOK
OMe
4a
Ph
tBuOH
MeO
tBuOH
O
Ph
Ph
O
(a) Gan, Y.; Zhang, N.H.; Huang, S.X.; Liu,Y.H. Nickel-Catalyzed
Cross-Coupling of Aryl Pivalates with Cyclobutanols Involving C-O and
C-C Bond Cleavage. Chin. J. Chem. 2020, 38, 1686-1690. (b) Mas-
son-Makdissi, J.; Vandavasi, J.K.; Newman, S.G. Switchable Selectivity
in the Pd-Catalyzed Alkylative Cross-Coupling of Esters. Org. Lett.
2018, 20, 4094–4098; (c) Zeng, H.Y.; Qiu, Z.H. An Adventure in Sus-
tainable Cross-Coupling of Phenols and Derivatives via Car-
bon-Oxygen Bond Cleavage. ACS Catal. 2017, 7, 510-519; (d) Shi-
masaki, T.; Tobisu, M.; Chatani, N. Nickel-Catalyzed Amination of Aryl
Pivalates by the Cleavage of Aryl C-O Bonds. Angew. Chem. Int. Ed.
2010, 49, 2929 –2932; (e) Antoft-Finch, A.; Blackburn, T.; Snieckus, V.
N, N-Diethyl O-Carbamate: Directed Metalation Group and Orthogo-
nal Suzuki-Miyaura Cross-Coupling Partner. J. Am. Chem. Soc. 2009,
131, 17750–17752; (f) Guan, B.T.; Wang, Y.; Li, B.J.; Yu, D.G.; Shi, Z.J.
Biaryl Construction via Ni-Catalyzed C-O Activation of Phenolic Car-
boxylates. J. Am. Chem. Soc. 2008, 130, 14468–14470; (g) Corbet, J.P.;
Mignani, G. Selected patented cross-coupling reaction technologies.
Chem. Rev. 2006, 106, 2651-2710; (h) Nguyen, H.N.; Huang, X.H.;
Buchwald, S.L. The first general palladium catalyst for the Suzu-
ki-Miyaura and carbonyl enolate coupling of aryl arenesulfonates. J.
Am. Chem. Soc. 2003, 125, 11818-11819; (i) Hassan, J.; Se´vignon, M.;
Gozzi, C.; Schulz, E.; Lemaire, M. Aryl-aryl bond formation one cen-
tury after the discovery of the Ullmann reaction. Chem. Rev. 2002,
102, 1359−1469; (j) Hamann, B.C.; Hartwig, J.F. Sterically hindered
chelating alkyl phosphines provide large rate accelerations in palla-
dium-catalyzed amination of aryl iodides, bromides, and chlorides,
and the first amination of aryl tosylates. J. Am. Chem. Soc. 1998, 120,
7369−7370.
Ph
3a
O
O
OMe
Ph
Ph
OMe
B
A
O
Ph
Ph
O
O
Ph
OMe
D
Ph
Ph
2a
Ph
O
O
OMe
Ph
Ph
C
Conclusions
We have developed an unprecedented base catalyzed [3+3]
annulation of β-ketoethers with cyclopropenones via C(sp3)-O and
C-C cleavage under mild conditions, giving various 2-pydones with
broad substrates scope and excellent chemoselectivity. This
method obviated the need of transition-metal catalysis and pro-
ceeded well with simple operation. The sp3 C-O bonds cleavage in
keto alkyl alkyl ethers and keto aryl alkyl ethers were realized in
this annulation reaction. Further efforts will be made to apply the
present strategy to the conversion of the nature lignin.
Experimental
Selected reviews of C-O activation: (a) Qiu, Z.H.; Li, C.J. Transformations of
Less-Activated Phenols and Phenol Derivatives via C-O Cleavage. Chem.
Rev. 2020, 120, 10454-10515; (b) Yu, D.G.; Li, B.J.; Shi, Z.J. Exploration of
New C-O Electrophiles in Cross-Coupling Reactions. Acc. Chem. Res. 2010,
43, 1486-1495; (c) Lin, Y.S.; Yamamoto, A. Activation of C-O Bonds: Stoi-
chiometric and Catalytic Reactions. Topics in organometallic Chemistry,
1999, 3, 161-192.
Selected reviews of lignin transformation: (a) Schutyser, W.; Renders, T.;
Van den Bosch, S.; Koelewijn, S.F.; Beckham, G.T.; Sels, B.F. Chemicals
from lignin: an interplay of lignocellulose fractionation, depolymerisation,
and upgrading. Chem. Soc. Rev. 2018, 47, 852-908; (b) Sun, Z.H.; Fridrich,
B.; Santi, A.D.; Elangovan, S.; Barta, K. Bright Side of Lignin Depolymeriza-
tion: Toward New Platform Chemicals. Chem. Rev. 2018, 118: 614–678; (c)
Upton, B.M.; Kasko, A.M. Strategies for the Conversion of Lignin to
High-Value Polymeric Materials: Review and Perspective. Chem. Rev. 2016,
116: 2275–2306; (d) Deuss, P.J.; Barta, K. From models to lignin: Transi-
tion metal catalysis for selective bond cleavage reactions. Coord. Chem.
Rev. 2016, 306: 510-532; (e) Li, C.Z.; Zhao, X.C.; Wang, A.Q.; Huber, G.W.;
Zhang T. Catalytic Transformation of Lignin for the Production of Chemi-
cals and Fuels. Chem. Rev. 2015, 115: 11559–11624; (f) Zakzeski, J.;
Bruijnincx, P.C.A.; Jongerius, A.L.; Weckhuysen, B.M. The Catalytic Valori-
zation of Lignin for the Production of Renewable Chemicals. Chem. Rev.
2010, 110, 3552-3599.
General procedure：tBuOK (2.24 mg, 0.02 mmol) in DME (2.0
mL) were charged into a pressure tube under argon, followed by
addition of cyclopropenone (0.200 mmol, 1.0 equiv) and ke-
toether (0.200 mmol, 1.0 equiv). The reaction tube was then
sealed and placed into an oil bath at 30 oC. After reaction for 36 h,
the reaction mixture was filtered through a pad of celite. The
mixture was eluted with ethyl acetate, concentrated, and purified
by silica gel chromatography (PE : EA = 10:1) to give the indicated
product.
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2021xxxxx.
Acknowledgement
This work is supported by the NSFC (Nos. 21801067,
U1804283, 21801066), the Central Plains Scholars and Scientists
Studio Fund (2018002), and the Project funded by the Natural
Science Foundation of Henan (202300410225, 212300410181 and
201901023) and China Postdoctoral Science Foundation
Selected examples of C-O bonds cleavage in lignin model compounds: (a)
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, XXX－XXX

Running title
Chin. J. Chem.
Zhang, B.; Qi, Z.J.; Li, X.X.; Ji, J.W.; Luo, W.H.; Li, C.Z.; Wang, A.Q.; Zhang, T.
A.M.; Cui, Y.B.; Alherech, M.; Stahl, S.S.; Jackson, J.E.; Hegg, E.L. Nucleo-
philic Thiols Reductively Cleave Ether Linkages in Lignin Model Polymers
and Lignin. ChemSusChem 2020, 13, 4394-4399; (c) Yang, C.; Kärkäs, M.D.;
Magallanes, G.; Chan, K.; Stephenson, C.R.J. Organocatalytic Approach to
Photochemical Lignin Fragmentation. Org. Lett. 2020, 22, 8082–8085; (d)
Klinger, G.E.; Zhou, Y.T.; Hao, P.C.; Robbins, J.; Aquilina, J.M.; Jackson, J.E.;
Hegg, E.L. Biomimetic Reductive Cleavage of Keto Aryl Ether Bonds by
Small-Molecule Thiols. ChemSusChem 2019, 12, 4775-4779.
(a) Raiguru, B.P.; Nayak, S.; Mishra, D.R.; Das, T.; Mohapatra, S.; Mishra,
N.P. Synthetic Applications of Cyclopropene and Cyclopropenone: Recent
Progress and Developments. Asian J. Org. Chem. 2020, 9, 1088-1132; (b)
Nakamura, M.; Isobe, H.; Nakamura, E. Cyclopropenone acetals synthesis
and reactions. Chem. Rev. 2003, 103, 1295-1326.
(a) Haito, A.; Chatani, N. Rh(I)-Catalyzed [3+2] annulation reactions of cy-
clopropenones with amides. Chem. Commun. 2019, 55, 5740-5742; (b)
Ren, J.T.; Wang, J.X.; Tian, H.; Xu, J.L.; Hu, H.; Aslam, M.; Sun, M.
Ag(I)-Catalyzed [3+2]-Annulation of Cyclopropenones and Formamides via
C-C Bond Cleavage. Org. Lett. 2018, 20, 6636–6639; (c) Li, X.; Han, C.; Yao,
H.; Lin, A. Organocatalyzed [3+2] Annulation of Cyclopropenones and
β-Ketoesters: An Approach to Substituted Butenolides with a Quaternary
Center. Org. Lett. 2017, 19, 778-781; (d) Wei, Y.; Zhao, W.; Yang, Y.; Zhang,
Z.; Shi, M. Allenic Esters from Cyclopropenones by Lewis Base Catalysis:
Substrate Scope, the Asymmetric Variant from the Dynamic Kinetic
Asymmetric Transformation, and Mechanistic Studies. ChemCatChem
2015, 7, 3340-3349.
(a) Shin, H.J.; Lee, H.S.; Lee, J.S.; Shin, J.; Lee, M.A.; Lee, H.S.; Lee, Y.J.;
Yun, J.; Kang, J.S. Violapyrones H and I, New Cytotoxic Compounds Isolat-
ed from Streptomyces sp Associated with the Marine Starfish Acanthaster
planci. Mar. Drugs 2014, 12, 3283-3291; (b) McGlacken, G.P.; Fairlamb,
I.J.S. 2-Pyrone natural products and mimetics: isolation, characterisation
and biological activity. Nat. Prod. Rep. 2005, 22, 369-385; (c) Wang, F.; Luo,
D.Q.; Liu, J.K.; Aurovertin E, a new polyene pyrone from the basidiomy-
cete Albatrellus confluens. J. Antibiot. 2005, 58, 412–415.
ReOx/AC-Catalyzed Cleavage of C-O Bonds in Lignin Model Compounds
and Alkaline Lignins. ACS Sustainable Chem. Eng. 2019, 7, 208−215; (b) Li,
H.L.; Song, G.Y. Ru-Catalyzed Hydrogenolysis of Lignin: Base-Dependent
Tunability of Monomeric Phenols and Mechanistic Study. ACS Catal. 2019,
9, 4054−4064; (c) Kim, J.; Kim, K.H.; Kwon, E.E. Enhanced thermal cracking
of VOCs evolved from the thermal degradation of lignin using CO2. Energy
2016, 100, 51-57; (d) Gregorio, D.; Prado, R.; Vriamont, C.; Erdocia, X.; La-
bidi, J.; Hallett, J.P.; Welton, T. Oxidative Depolymerization of Lignin Using
a Novel Polyoxometalate-Protic Ionic Liquid System. ACS Sustainable
Chem. Eng. 2016, 4, 6031-6036; (e) Haibach, M.C.; Lease, N.; Goldman, A.S.
Catalytic Cleavage of Ether C-O Bonds by Pincer Iridium Complexes. An-
gew. Chem. Int. Ed. 2014, 53, 10160 –10163; (f) Fan, H.L.; Yang, Y.Y.; Song,
J.L.; Ding, G.D.; Wu, C.Y.; Yang, G.Y.; Han, B.X. One-pot sequential oxida-
tion and aldol-condensation reactions of veratryl alcohol catalyzed by the
Ru@ZIF-8+CuO/basic ionic liquid system. Green Chem. 2014, 16, 600-604;
(g) Zhang, J.; Liu, Y.; Chiba, S.; Loh, T.P. Chemical conversion of beta-O-4
lignin linkage models through Cu-catalyzed aerobic amide bond formation.
Chem. Commun. 2013, 49, 11439-11441.
(a) Ji, J.W.; Guo, H.W.; Li, C.Z.; Qi, Z.J.; Zhang, B.; Dai, T.; Jiang, M.; Ren,
C.R.; Wang, A.Q.; Zhang, T. Tungsten-Based Bimetallic Catalysts for Selec-
tive Cleavage of Lignin C-O Bonds. ChemCatChem 2018, 10, 415-421; (b)
Deuss, P.J.; Scott, M.; Tran, F.; Westwood, N.J.; de Vries, J.G.; Barta, K.
Aromatic Monomers by in Situ Conversion of Reactive Intermediates in
the Acid-Catalyzed Depolymerization of Lignin. J. Am. Chem. Soc. 2015,
137, 7456–7467; (c) Gao, Y.J.; Zhang, J.G.; Chen, X.; Ma, D.; Yan, N. A Met-
al-Free, Carbon-Based Catalytic System for the Oxidation of Lignin Model
Compounds and Lignin. ChemPlusChem 2014, 79, 825-834.
(a) Chatel, G.; Rogers, R.D. Review: Oxidation of Lignin Using Ionic Liq-
uids-An Innovative Strategy To Produce Renewable Chemicals. ACS Sus-
tainable Chem. Eng. 2014, 2, 322–339; (b) Kang, Y.; Lu, X.M.; Zhang, G.J.;
Yao, X.Q.; Xin, J.Y.; Yang, S.Q.; Yang, Y.Q.; Xu, J.L.; Feng, M.; Zhang, S.J.
Metal-Free Photochemical Degradation of Lignin-Derived Aryl Ethers and
Lignin by Autologous Radicals through Ionic Liquid Induction. ChemSus-
Chem 2019, 12, 4005-4013; (c) Yang, Y.Y.; Fan, H.L.; Meng, Q.L.; Zhang,
Z.F.; Yang, G.Y.; Han, B.X. Ionic liquid [OMIm][OAc] directly inducing oxi-
dation cleavage of the beta-O-4 bond of lignin model compounds. Chem.
Commun. 2017, 53, 8850-8853.
(a) Wang, Y.L.; Du, Y.M.; He, J.H.; Zhang, Y.T. Transformation of lignin
model compounds to N-substituted aromatics via Beckmann rearrange-
ment. Green Chem. 2018, 20, 3318-3326; (b) Wang, Y.L.; Wang, Q.Y.; He,
J.H.; Zhang, Y.T. Highly effective C-C bond cleavage of lignin model com-
pounds. Green Chem. 2017, 19, 3135-3141.
(a) Liu, H.F.; Zhu, L.L.; Wallraf, A.M.; Rauber, C.; Grande, P.M.; Anders, N.;
Gertler, C.; Werner, B.; Klankermayer, J.; Leitner, W.; Schwaneberg, .U.
Depolymerization of Laccase-Oxidized Lignin in Aqueous Alkaline Solution
at 37 degrees C. ACS Sustainable Chem. Eng. 2019, 7, 11150–11156; (b)
Rahimi, A.; Ulbrich, A.; Coon, J.J.; Stahl, S.S. Formic-acid-induced depoly-
merization of oxidized lignin to aromatics. Nature 2014, 515, 249–252.
(a) Bai, D.C.; Yu, Y.J.; Guo, H.M.; Chang, J.B.; Li, X.W. Nick-
el(0)-Catalyzed Enantioselective [3+2] Annulation of Cycloprope-
nones and α,β-Unsaturated Ketones/Imines. Angew. Chem. Int. Ed.
2020, 59, 2740-2744; (b) Haito, A.; Chatani, N. Rh(I)-Catalyzed [3+2]
annulation reactions of cyclopropenones with amides. Chem. Com-
mun. 2019, 55, 5740-5742.
(a) Zhen, F.; Flynn, M.G.; Jackson, J.E.; Hegg, E.L. Thio-assisted reductive
electrolytic cleavage of lignin beta-O-4 models and authentic lignin. Green
Chem. 2021, 23, 412-421; (b) Klinger, G.E.; Zhou, Y.T.; Foote, J.A.; Wester,
Chin. J. Chem. 2021, 39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de

Entry for the Table of Contents
Catalytic [3+3] Annulation of β-Ketoethers and Cyclopropenones via C(sp3)-O/C-C Bond Cleavage Under Transition-metal Free Conditions
Dachang Bai, *,abJunyan Chen,a Bingbing Zheng,a Xueyan Li,a Junbiao Chang *,a
Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
O
O
R3
R3
R3
R3
O
O
O
cat. tBuOK
cat. tBuOK
R2
+
O
R2
+
O
O
R2OH
R3
O
Ar
+
R3
R2 Me
R2 Ar
=
=
R3
Ar
Ar
R3
R1
R1
R1
•
•
•
•
reaction
annulation
Transition-metal free catalysis C-C/C-O bond cleavage
[3+3]
•
•
scope
Broad substrate
Excellent chemoselectivity Mild reaction condition
Text for Table of Contents.
a NMPA Key Laboratory for Research and Evaluation of Innovative b State Key Laboratory of Organometallic Chemistry, Shanghai In-
Drug, Collaborative Innovation Center of Henan Province for Green stitute of Organic Chemistry, Chinese Academy of Sciences, Shang-
Manufacturing of Fine Chemicals, School of Chemistry and Chemi- hai 200032, P R China
cal Engineering, Henan Normal University, Xinxiang 453007 (Chi-
na)
E-mail: baidachang@htu.edu.cn; changjunbiao@zzu.edu.cn
Chin. J. Chem. 2018, template
© 2018 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim