Dearomative [4+2] Cycloaddition of Oxindole-Embedded ortho-Quinone Methides with 2,5-Dialkylfurans

Article abstract of DOI:10.1002/adsc.201801509

2,5-Dialkylfurans were facilely converted to pharmaceutically significant spiro[chroman-4,3′-oxindole] scaffolds via an organocatalytic dearomative [4+2] cycloaddition with oxindole-embedded ortho-quinone methides. This method featured mild reaction conditions, simple operation, good yields, and excellent diastereoselectivities.

Full text of DOI:10.1002/adsc.201801509

Title: Dearomative [4+2] Cycloaddition of Oxindole-Embedded ortho-
Quinone Methides with 2,5-Dialkylfurans
Authors: Yao-Bin Shen, Shuai-Shuai Li, Xicheng Liu, Liping Yu, Qing
Liu, and Jian Xiao
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801509
Link to VoR: http://dx.doi.org/10.1002/adsc.201801509

10.1002/adsc.201801509
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Dearomative [4+2] Cycloaddition of Oxindole-Embedded ortho-
Quinone Methides with 2,5-Dialkylfurans
Yao-Bin Shen,a Shuai-Shuai Li,a Xicheng Liu,c Liping Yu,b* Qing Liu,d Jian Xiaoa*
a
College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266109, China
E-mail: lipingyu99@163.com; chemjianxiao@163.com
College of Landscape Architecture and Forestry, Qingdao Agricultural University, Qingdao 266109, China
College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China
College of Chemical and Environmental Engineering, Shandong University of Science and Technology, Qingdao
b
c
d
266590, China
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
contribution as core structures of numerous naturally
occurring and medicinal molecules (Figure 1).
Consequently, it is appealing to develop new
synthons and cyclization strategies for one-step
Abstract. 2,5-Dialkylfurans were facilely converted to
pharmaceutically significant spiro[chroman-4,3'-oxindole]
scaffolds via an organocatalytic dearomative [4+2]
cycloaddition with oxindole-embedded ortho-quinone
methides. This method featured mild reaction conditions,
construction
of
spiro[chroman-4,3'-oxindole]
simple
operation,
good
yields,
and
excellent
scaffolds from readily available starting materials.
ortho-Quinone methides (o-QMs) are highly
reactive intermediates for the synthesis of complex
natural products and bioactive compounds.[5] With
rearomatization as a driving force, o-QMs typically
serve as electron-deficient dienes to participate in
diastereoselectivities.
Keywords: 2,5-dialkylfuran; spirooxindole; oxindole-
embedded o-QMs; dearomatization; [4+2] cycloaddition
inverse-electron-demand
hetero-Diels−Alder
(IED−HDA) reactions (Scheme 1a).[6] However, the
limited kinds of o-QMs and dienophiles restricted
their applications in the assembly of molecular
diversity and complexity, which posed a formidable
challenge. To address this challenge, we rationally
designed a new type of oxindole-embedded o-QMs
and envisaged that a dearomative [4+2] cycloaddition
of these o-QMs with 2,5-dialkylfurans would occur,
Spirooxindoles are privileged structural motifs in a
wide range of natural products and pharmaceuticals
with intriguing bioactivities (Figure 1).[1] Owing to
their great significance, a large number of protocols
have been developed to build up such scaffolds.[2] For
instance, a quantity of methods dealt with the
construction
of
spiro[chroman-3,3'-oxindole]
thus providing
a
new synthetic option to
frameworks via an oxa-Michael-Michael cyclization,
in which oxindole components served as 2π
synthons.[3] Nevertheless, there are only sporadic
reports with regard to the assembly of spiro[chroman-
4,3'-oxindole] scaffolds,[4] in spite of their significant
spiro[chroman-4,3´-oxindole] scaffolds (Scheme 1b).
In this strategy, 2,5-dialkylfurans would act as novel
Scheme 1. IED-HDA reaction of o-QMs and dearomative
[4+2] cycloaddition of oxindole-embedded o-QMs with
2,5-dialkylfurans.
Figure 1. Representative bioactive molecules containing
spirooxindoles.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801509
Advanced Synthesis & Catalysis
Table 1. Optimization of the reaction conditions[a]
the catalyst loading was evaluated, and the yield of
3a could be increased to 85% when the catalyst
loading was decreased to 10 mol% (Table 1, entries
11-12). The final solvent screening implied that DCE
was the best solvent for this reaction (Table 1, entries
13-18).
Entry
1
2
3
4
5
6
7
8
Catalyst
TfOH
p-TSA·H2O
MsOH
Solvent Time Yield[b] (%)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
THF
10 s
1 h
0.1 h
2 d
1 d
2 d
2 d
2 d
1 h
4 h
28
82
67
40
74
18
0
0
77
0
TFA
(−
)-CSA
PA
PhCO2H
AcOH
Sc(OTf)3
Cu(OTf)2
9
10
11[c] p-TSA·H2O
12[d] p-TSA·H2O
13[c] p-TSA·H2O
14[c] p-TSA·H2O
2 h
5 h
1.3 h
2 d
85
81
80
0
15[c] p-TSA·H2O Toluene 5 h
61
27
0
16[c] p-TSA·H2O MeCN
2 d
2 d
2 d
17[c] p-TSA·H2O
18[c] p-TSA·H2O
EtOH
H2O
0
[a]
Reaction conditions (unless otherwise noted): 1a (0.1
mmol), 2a (0.3 mmol), catalyst (20 mol%), solvent (1
mL), room temperature. (−)-CSA
=
(−)-10-
camphorsulfonic acid. PA=1,1'-binaphthyl-2,2'-diyl
hydrogen phosphate.
Scheme 2. Substrate scope for dearomative [4+2]
cycloaddition of oxindole-embedded o-QMs 1 with 2,5-
dimethylfuran 2a. [a] Reaction conditions: 1 (0.1 mmol), 2a
[b] Isolated yield, dr >20:1.
[c] Catalyst (10 mol%).
[d] Catalyst (5 mol%).
(0.3 mmol), p-TSA·H2O (10 mol%), DCE (1 mL), room
temperature. Isolated yields after column chromatography.
1
The dr was determined by H NMR analysis, dr >20:1 in
dienophiles while oxindole-embedded o-QMs served
as new four-membered building blocks. However, it
is noteworthy that a competitive conjugate addition of
electron-rich 2,5-dialkylfurans to o-QMs might take
place.[7] As a continuation of our research interest in
one-step assembly of biological active molecules,[8]
herein, we reported an organocatalytic dearomative
[4+2] cycloaddition of oxindole-embedded o-QMs
all cases. [b] p-TSA
·H2O (20 mol%).
With the optimized reaction conditions in hand, the
substrate scope was investigated (Scheme 2).
Generally, a wide range of oxindole-embedded ortho-
hydroxybenzyl alcohols 1 with various R1/R2/R3
groups proceeded smoothly in this reaction,
delivering the corresponding products 3 in high yields
with excellent diastereoselectivities (dr >20:1). As for
the R1 groups, both electron-donating and electron-
withdrawing substituents were well tolerated and
provided products 3a-3j in high yields. The positions
of substituents had trivial impacts on the yields
except 3e and 3h, the lower yields of which might be
attributed to the steric hindrance. Notably, the success
of fluorine-substituted products 3c and 3d indicated
the potential applicability in synthesis of fluorine-
containing drugs. With respect to the R2 groups, in
addition to methyl and ethyl groups, cyclopropyl and
cyclopropylmethyl substituents with severe ring
strain were also compatible with the reaction
conditions and gave the desired products in 72%-84%
yields (3k-3n). Remarkably, substrates bearing
dienophilic allyl and propargyl moieties were
with
2,5-dialkylfurans,
furnishing
the
pharmaceutically important spiro[chroman-4,3'-
oxindole] scaffolds in high yields with excellent
diastereoselectivities under mild conditions.
To examine the feasibility of our hypothesis,
oxindole-embedded ortho-hydroxybenzyl alcohol 1a
and biomass-derived 2,5-dimethylfuran 2a[9] were
selected as model substrates to carry out this reaction
(Table 1). To our delight, this reaction proceeded
readily with 20 mol% TfOH as a catalyst in DCE at
room temperature, furnishing the cycloadduct 3a in
28% yield with high diastereoselectivity(dr >20:1)
(Table 1, entry 1). Afterwards, a series of Brønsted
acids and Lewis acids were screened, and it was
found that p-TSA·H2O was the optimal catalyst,
yielding 3a in 82% yield (Table 1, entries 2-10). Then
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801509
Advanced Synthesis & Catalysis
one was also performed and the cycloadduct 4f was
provided in 75% yield. It is worth mentioning that the
reactivity of 5-methylfuran-2(3H)-one serving as a
dienophile has never been reported. However, when
furan and 2-methylfuran were employed as the
reaction partners, the conjugate addition reactions
occurred and furnished 3,3-diaryl-substituted
oxindoles 4g and 4h in good yields.[12]
To shed light on the reaction mechanism, several
control experiments were performed (Scheme 4). To
verify the existence of our proposed oxindole-
embedded o-QMs, 1a was subjected to the standard
reaction conditions without 2,5-dimethylfuran. We
were pleased that the oxindole-embedded o-QM
intermediate 5a could be isolated, in a low yield,
which might be ascribed to the reversible dehydration
and hydrolysis processes (Scheme 4a). There are two
possible E/Z geometric isomers 5a and 5a', and 5a is
much more favored than 5a' due to the electrostatic
interaction and the steric repulsion between O/O
atoms. Moreover, failure to observe an NOE signal
between Ha and Hb further confirmed the
predominance of geometric isomer 5a (See
Supporting Information). When intermediate 5a was
subjected to the reaction conditions with the addition
of water, the desired product 3a was delivered in 75%
yield (Scheme 4b). Gratifyingly, other oxindole-
embedded o-QMs 5b, 5c and 5f could also be isolated
and applied to these reactions (See Supporting
Information). However, when the hydroxyl group of
phenol was protected with a benzyl group, no
reaction occurred under the standard reaction
conditions, since the generation of oxindole-
embedded o-QM 5a was obstructed (Scheme 4c).
Figure 2. X-ray structure of 3r.
tolerable as well, exhibiting the excellent selectivity
and specificity of this transformation (3o-3p).
Satisfyingly,
the
oxindole-embedded
ortho-
naphthoquinone methides (o-NQMs)[10] also reacted
smoothly and afforded products 3q and 3r in good
yields. The relative configuration of 3r was
unambiguously confirmed by X-ray crystallography
(Figure 2).[11]
Afterwards, a few other furan derivatives were
examined, as shown in Scheme 3. To our delight, the
dearomative [4+2] cycloaddition of oxindole-
embedded o-QMs 1 with various 2-benzhydryl-5-
alkylfurans proceeded very well via an IED-HDA
Scheme 3. Substrate scope for dearomative [4+2]
cycloaddition of oxindole-embedded o-QMs 1 with furan
[a]
derivatives 2. Reaction conditions: 1 (0.1 mmol), 2 (0.3
mmol), p-TSA·H2O (10 mol%), DCE (1 mL), room
Scheme 4. Control experiments.
temperature. Isolated yields after column chromatography.
1
The dr was determined by H NMR analysis, dr >20:1 for
[b]
products 4a-4f. p-TSA·H2O (20 mol%). 5-Methylfuran-
On the basis of the above experiments, a plausible
reaction mechanism was proposed (Scheme 5).
Initially, the oxindole-embedded o-QM intermediate
5 is in situ generated via the dehydration of 1 in the
presence of Brønsted acid, which undergoes
subsequent IED−HDA reaction with 2,5-dialkylfuran
2. In this process, there are two possible transition
states endo TS 1 and exo TS 2. Due to the unique
2(3H)-one was used.
/tautomerization process, giving the corresponding
products 4a-e in 74-84% yields. Moreover, in view of
the fact that 5-methylfuran-2(3H)-one could be
tautomerized to 5-methylfuran-2-ol under acidic
conditions, the reaction with 5-methylfuran-2(3H)-
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801509
Advanced Synthesis & Catalysis
structure of the oxindole-embedded o-QMs, the π-π
interaction of the unreacted C=C bond in 2,5-
dialkylfuran with the phenyl ring in oxindole unit (TS
2) is stronger than that with the diene in sesamol
moiety (TS 1). Thus the unusual exo TS 2 is much
more favored, furnishing the intermediate 7. When
2,5-dimethylfuran is employed, it undergoes
hydrolysis to afford the desired product 3. On the
other hand, the tautomerization of 7 would operate to
give product 4 if 2-benzhydryl-5-methylfuran is
utilized, which might be ascribed to the formation of
more stable conjugate system.
4,3'-oxindole] scaffolds in high yields with excellent
diastereoselectivities under mild conditions. In this
strategy, 2,5-dialkylfurans served as novel
dienophiles, and oxindole-embedded o-QMs acted as
new four-membered building blocks, which will push
forwards the chemistry of o-QMs in the synthesis of
biologically important compounds.
Experimental Section
General Experimental Procedures for the Synthesis of 3
or 4. An oven-dried reaction tube was charged with
oxindole-embedded ortho-hydroxybenzyl alcohol 1 (1.0
equiv, 0.1 mmol), p-TSA·H2O (10 mol%), DCE (1 mL)
and 2,5-dialkylfuran 2 (3.0 equiv, 0.3 mmol). The reaction
mixture was stirred vigorously at room temperature and
monitored by TLC. After the consumption of 1, the
reaction mixture was directly purified by flash column
chromatography
(column
chromatography
eluent,
petroleum ether/ethyl acetate) to afford products 3 or 4.
Acknowledgements
We are grateful to NSFC (21702117, 21878167) and the Natural
Science Foundation of Shandong Province (JQ201604,
ZR2017BB005) as well as the Key Research and Development
Program of Shandong Province (2017GSF218073). We thank Dr
Feng-Ying Dong (the Central Laboratory of Qingdao
Agricultural University) for NMR determination.
Scheme 5. Proposed mechanism.
References
To further demonstrate the synthetic utility of this
protocol, the scalability of the method was examined,
providing 3o in 75% yield with a maintenance of the
excellent diastereoselectivity (Scheme 6a). In
addition, a Wittig reaction of 3o afforded α, β-
unsaturated ester 8 in 72% yield with high E/Z
selectivity, and an interesting ketal product 9 could be
[1] a) G. S. Singh, Z. Y. Desta, Chem. Rev. 2012, 112,
6104; b) C. V. Galliford, K. A. Scheidt, Angew. Chem.
Int. Ed. 2007, 46, 8748; c) H. Lin, S. J. Danishefsky,
Angew. Chem. Int. Ed. 2003, 42, 36; d) P. Eastwood, J.
González, E. Gómez, F. Caturla, N. Aguilar, M. Mir, J.
Aiguadé, V. Matassa, C. Balagué, A. Orellana, M.
Domínguez, Bioorg. Med. Chem. Lett. 2011, 21, 6253;
e) P. J. D. Dollings, A. F. Donnell, A. M. Gilbert, M.
Zhang, B. L. Harrison, C. J. Stanton, S. V. O’Neil, L.
M. Havran, D. C. Chong, PCT Int. Appl. 2010,
WO2010077839; f) S. Wang, Y. Jiang, S. Wu, G. Dong,
Z. Miao, W. Zhang, C. Sheng, Org. Lett. 2016, 18,
1028.
obtained
in
51%
yield
with
excellent
diastereoselectivity when ethanol was added (Scheme
6b).
[2] For reviews, see: a) G.-J. Mei, F. Shi, Chem. Commun.
2018, 54, 6607; b) J. Bariwal, L. G. Voskressensky, E.
V. Van der Eycken, Chem. Soc. Rev. 2018, 47, 3831; c)
A. Ding, M. Meazza, H. Guo, J. W. Yang, R. Rios,
Chem. Soc. Rev. 2018, 47, 5946; d) Z.-Y. Cao, F. Zhou,
J. Zhou, Acc. Chem. Res. 2018, 51, 1443; e) R. Narayan,
M. Potowski, Z.-J. Jia, A. P. Antonchick, H. Waldmann,
Acc. Chem. Res. 2014, 47, 1296; f) Z.-Y. Cao, J. Zhou,
Org. Chem. Front. 2015, 2, 849; g) D. Cheng, Y.
Ishihara, B. Tan, C. F. Barbas, III, ACS Catal. 2014, 4,
743; h) L. Hong, R. Wang, Adv. Synth. Catal. 2013,
355, 1023; i) M. M. M. Santos, Tetrahedron 2014, 70,
9735; For representative examples, see: j) X.-L. He, H.-
R. Zhao, C.-Q. Duan, W. Du, Y.-C. Chen, Org. Lett.
2018, 20, 804; k) Y. Kuang, B. Shen, L. Dai, Q. Yao, X.
Liu, L. Lin, X. Feng, Chem. Sci. 2018, 9, 688; l) J.-Q.
Scheme 6. Gram-scale synthesis and derivatization of
product 3o.
In conclusion, we have developed an
organocatalytic dearomative [4+2] cycloaddition of
oxindole-embedded o-QMs with 2,5-dialkylfurans,
furnishing the biologically important spiro[chroman-
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801509
Advanced Synthesis & Catalysis
Zhao, X.-J. Zhou, Y. Zhou, X.-Y. Xu, X.-M. Zhang,
Panek, S. E. Schaus, Org. Lett. 2017, 19, 1878; f) Z.
Wang, J. Sun, Org. Lett. 2017, 19, 2334; g) J.-J. Zhao,
S.-B. Sun, S.-H. He, Q. Wu, F. Shi, Angew. Chem. Int.
Ed. 2015, 54, 5460; h) C.-C. Hsiao, S. Raja, H.-H. Liao,
I. Atodiresei, M. Rueping, Angew. Chem. Int. Ed. 2015,
54, 5762; i) X. Wu, L. Xue, D. Li, S. Jia, J. Ao, J. Deng,
H. Yan, Angew. Chem. Int. Ed. 2017, 56, 13722.
W.-C. Yuan, Org. Lett. 2018, 20, 909; m) D.-F. Yue,
J.-Q. Zhao, Y.-Z. Chen, X.-M. Zhang, X.-Y. Xu, W.-C.
Yuan, Adv. Synth. Catal. 2018, 360, 1420; n) W. He, J.
Hu, P. Wang, L. Chen, K. Ji, S. Yang, Y. Li, Z. Xie, W.
Xie, Angew. Chem. Int. Ed. 2018, 57, 3806; o) Y.-M.
Wang, H.-H. Zhang, C. Li, T. Fan, F. Shi, Chem.
Commun. 2016, 52, 1804; p) T. Fan, H.-H. Zhang, C.
Li, Y. Shen, F. Shi, Adv. Synth. Catal. 2016, 358, 2017;
q) X.-L. Jiang, S.-J. Liu, Y.-Q. Gu, G.-J. Mei, F. Shi,
Adv. Synth. Catal. 2017, 359, 3341; r) G.-J. Mei, D. Li,
G.-X. Zhou, Q. Shi, Z. Cao, F. Shi, Chem. Commun.
2017, 53, 10030; s) F. Shi, G.-J. Xing, R.-Y. Zhu, W.
Tan, S. Tu, Org. Lett. 2013, 15, 128; t) B.-L. Zhao, D.-
M. Du, Org. Lett. 2018, 20, 3797.
[7] a) J.-L. Wu, J.-Y. Wang, P. Wu, G.-J. Mei, F. Shi, Org.
Chem. Front. 2017, 4, 2465; b) W. Zhao, Z. Wang, B.
Chu, J. Sun, Angew. Chem. Int. Ed. 2015, 54, 1910; c)
S. Saha, S. K. Alamsetti, C. Schneider, Chem. Commun.
2015, 51, 1461; d) T. P. Pathak, K. M. Gligorich, B. E.
Welm, M. S. Sigman, J. Am. Chem. Soc. 2010, 132,
7870.
[8] a) S.-S. Li, X. Lv, D. Ren, C.-L. Shao, Q. Liu, J. Xiao,
Chem. Sci. 2018, 9, 8253; b) Y.-B. Shen, S.-S. Li, L.
Wang, X.-D. An, Q. Liu, X. Liu, J. Xiao, Org. Lett.
2018, 20, 6069; c) S.-S. Li, L. Zhou, L. Wang, H. Zhao,
L. Yu, J. Xiao, Org. Lett. 2018, 20, 138; d) S. Wang,
X.-D. An, S.-S. Li, X. Liu, Q. Liu, J. Xiao, Chem.
Commun. 2018, 54, 13833; e) S. Zhu, C. Chen, M.
Xiao, L. Yu, L. Wang, J. Xiao, Green Chem. 2017, 19,
5653; f) M. Xiao, D. Ren, L. Xu, S.-S. Li, L. Yu, J.
Xiao, Org. Lett. 2017, 19, 5724; g) J. Xiao, H. Wen, L.
Wang, L. Xu, Z. Hao, C.-L. Shao, C.-Y. Wang, Green
Chem. 2016, 18, 1032; h) L. Xu, Z. Shao, L. Wang, J.
Xiao, Org. Lett. 2014, 16, 796; i) J. Xiao, Org. Lett.
2012, 14, 1716; j) R. Niu, J. Xiao, T. Liang, X. Li, Org.
Lett. 2012, 14, 676.
[3] a) K. Zhao, Y. Zhi, T. Shu, A. Valkonen, K. Rissanen,
D. Enders, Angew. Chem. Int. Ed. 2016, 55, 12104; b)
L. Zhu, Q. Chen, D. Shen, W. Zhang, C. Shen, X. Zeng,
G. Zhong, Org. Lett. 2016, 18, 2387; c) Y. Huang, C.
Zheng, Z. Chai, G. Zhao, Adv. Synth. Catal. 2014, 356,
579; d) D. B. Ramachary, M. S. Prasad, S. V. Laxmi, R.
Madhavachary, Org. Biomol. Chem. 2014, 12, 574; e)
H. Mao, A. Lin, Y. Tang, Y. Shi, H. Hu, Y. Cheng, C.
Zhu, Org. Lett. 2013, 15, 4062.
[4] a) S. Jia, Y. Lei, L. Song, A. G. K. Reddy, D. Xing, W.
Hu, Adv. Synth. Catal. 2017, 359, 58; b) L. Qiao, Z.-W.
Duan, X.-N. Wu, D.-H. Li, Q.-Q. Gu, Y.-K. Liu, Org.
Lett. 2018, 20, 1630.
[5] a) U. Pindur, H. Erfanian-Abdoust, Chem. Rev. 1989,
89, 1681; b) J. L. Segura, N. Martin, Chem. Rev. 1999,
99, 3199; c) W.-J. Bai, J. G. David, Z.-G. Feng, M. G.
Weaver, K.-L. Wu, T. R. R. Pettus, Acc. Chem. Res.
2014, 47, 3655; d) Q. Li, T. Dong, X. Liu, X. Zhang, X.
Yang, X. Lei, Curr. Org. Chem. 2014, 18, 86; e) L.
Caruana, M. Fochi, L. Bernardi, Molecules 2015, 20,
11733; f) W. Ai, D. Liao, X. Lei, Chin. J. Org. Chem.
2015, 35, 1615; g) Z. Wang, J. Sun, Synthesis 2015, 47,
3629; h) T. P. Pathak, M. S. Sigman, J. Org. Chem.
2011, 76, 9210; i) N. J. Willis, C. D. Bray, Chem. Eur.
J. 2012, 18, 9160; j) B. Yang, S, Gao, Chem. Soc. Rev.
2018, 47, 7926.
[9] a) A. E. Settle, L. Berstis, N. A. Rorrer, Y. Roman-
Leshkóv, G. T. Beckham, R. M. Richards, D. R.
Vardon, Green Chem. 2017, 19, 3468; (b) B. Saha, M.
M. Abu-Omar, ChemSusChem 2015, 8, 1133; (c) Y.
Roman-Leshkóv, C. J. Barrett, Z. Y. Liu, J. A. Dumesic,
Nature 2007, 447, 982; (d) M. Chidambaram, A. T.
Bell, Green Chem. 2010, 12, 1253.
[10] D. Wu, X. Zhang, Y. Xu, Y. Xue, J. Li, W. Wang, J.
Zhu, Asian J. Org. Chem. 2014, 3, 480.
[11] CCDC 1871616 contains the supplementary
crystallographic data for 3r. These data can be obtained
free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[6] a) C. D. Gheewala, J. S. Hirschi, W.-H. Lee, D. W.
Paley, M. J. Vetticatt, T. H. Lambert, J. Am. Chem. Soc.
2018, 140, 3523; b) Y. Xie, B. List, Angew. Chem. Int.
Ed. 2017, 56, 4936; c) M. Liang, S. Zhang, J. Jia, C.-H.
Tung, J. Wang, Z. Xu, Org. Lett. 2017, 19, 2526; d) J.
Zhang, L. Lin, C. He, Q. Xiong, X. Liu, X. Feng, Chem.
Commun. 2018, 54, 74; e) E. E. Allen, C. Zhu, J. S.
[12] K. N. Babu, N. R. Kariyandi, S. S. M. K., L. K.
Kinthada, A. Bisai, J. Org. Chem. 2018, 83, 12664.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801509
Advanced Synthesis & Catalysis
UPDATE
Dearomative [4+2] Cycloaddition of Oxindole-
Embedded ortho-Quinone Methides with 2,5-
Dialkylfurans
Adv. Synth. Catal. Year, Volume, Page – Page
Yao-Bin Shen,a Shuai-Shuai Li,a Xicheng Liu,c
Liping Yu,b*Qing Liu,d Jian Xiaoa*
6
This article is protected by copyright. All rights reserved.