Synthesis of polycyclic spirooxindoles via an asymmetric catalytic one-pot stepwise Aldol/chloroetherification/aromatization procedure

Article abstract of DOI:10.1039/C8OB01713A

A general method for the synthesis of chiral pentacyclic spirooxindoles containing a tetrahydropyrano[2,3-b]indole scaffold through a one-pot stepwise sequence from 3-(3-indolomethyl)oxindole, paraformaldehyde and NCS is reported. Furthermore, the pentacyclic spirooxindoles could be transformed to bispirooxindole and other structurally diverse spirocyclic oxindoles.

Full text of DOI:10.1039/C8OB01713A

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DOI: 10.1039/C8OB01713A
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Synthesis of Polycyclic Spirooxindoles via Asymmetric Catalytic
One-pot Stepwise Aldol/ Chloroetherification/Aromatization
Procedure
Received 00th January 20xx,
Accepted 00th January 20xx
Yan Jiang,*a,b Shuo-Wen Yu,b Yi Yang,a Ying-Le Liu,a Xiao-Ying Xu,b Xiao-Mei Zhang [b] and Wei-
Cheng Yuan*b
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
general method for the synthesis of chiral pentacyclic
spirooxindoles containing tetrahydropyrano[2,3-b]indole scaffold
through one-pot stepwise sequence from 3-(3-
a
indolomethyl)oxindole, paraformaldehyde and NCS is reported.
Furthermore, the pentacyclic spirooxindoles could be transformed
to bispirooxindole and other structurally diverse spirocyclic
oxindole.
Chiral spirooxindoles, as a class of very important alkaloids, are
widely found in natural products, biologically active molecules
and drugs. [1] Such as spirotryprostatin A and spirotryprostatin
B, anti-tumor candidate MI147, analgesic drugs (-)-Horsfiline,
contain the backbone of spirooxindoles. For another,
compounds containing indole skeleton are corresponding with
a wide range of biological activity.[2] Furthermore, some
sophisticated structures in which the spirooxindole core is fused
with a indole moiety at the C3-position were documented as
possessing remarkable biological activities.[3] Because of the
significant medicinal value and structural complexities, these
intriguing frameworks have emerged as attractive synthetic
targets[3a, 4] and numerous methodologies for the construction
of diverse spirooxindole molecules have been exploited.[5]
The development of one-pot multicomponent stepwise
synthetic methodologies for the tailor-made construction of
enantioenriched compounds from simple and readily available
starting materials is a highly pursued area in chemical synthesis
since they reduce the generation of waste by avoiding multiple
separation steps and purification of intermediates.[6]
Scheme 1. A New One-pot Reaction Sequence by the Methodological
Combination.
Asymmetric catalytic nucleophilic addition of 3-substituted
oxindoles have been reported as a straightforward and mature
route to highly functionalized chiral 3,3-disubstituted
oxindoles.[7] Otherwise, the intramolecular electrophilic
halocyclization of olefins is a widely used fundamental organic
transformation for the construction of heterocycles.[8]
Therefore, we discovered a new one-pot stepwise reaction
sequence for the construction of spirooxindole, based on the
combination of nucleophilic addition of 3-substituted oxindoles
and intramolecular electrophilic halocyclization of olefins
(Scheme 1). By introducing an alkene group on the C3 position
of oxindole in advance, then the catalytic one-pot nucleophilic
addition/ halogenation/ cyclization could be proceeding
smoothly to getting the desired spirooxindoles. According to
the new one-pot synthetic method, we designed a catalytic one-
pot sequential Aldol/ chloroetherification/aromatization of 3-
(3-indolomethyl)oxindoles to synthesis of pentacyclic
spirooxindoles (Scheme 2).
a.School of Chemistry and Environmental Engineering, Sichuan University of Science
& Engineering, Zigong 643000, China. E-mail: jiangyan199@126.com
b.National Engineering Research Center of Chiral Drugs, Chengdu Institute of
Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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Journal Name
Entrya Cat. solvent
DABCO
T
Time VYieiwelAdrticleEOenline
DOI: 10.1039/C8OB01713A
(oC) (h)
(%)b
72
(%)c
91
88
62
78
93
87
84
95
95
1
3a
3b
3c
3d
3a
3a
3a
3a
3a
3a
DCM
DCM
DCM
DCM
DCE
1.2 equiv
1.2 equiv
1.2 equiv
1.2 equiv
1.2 equiv
1.2 equiv
1.2 equiv
1.2 equiv
1.2 equiv
0
rt.
rt.
rt.
rt.
rt.
rt.
rt.
0
24
24
24
24
23
17
27
46
74
46
Scheme
2
.
Catalytic
Asymmetric
One-pot
Sequencial
2
64
Aldol/Chloroetherification/Aromatization of 3-(3-indolomethyl)oxindoles to
Synthesis of Pentacyclic Spirooxindoles.
3
79
4
74
5
72
To test the validation of this design, 3-(3-indolomethyl)oxindole
(1a) was chosen as a model substrate for investigation. On the
6
CHCl3
Toluene
DCE
44
basis of the wide use of bifunctional tertiary amine-thiourea and
chiral tertiary amine in the asymmetric catalytic Aldol reaction
of oxindoles[9] and electrophilic halocyclization of olefins[10], we
initially used tertiary amine-thiourea or chiral tertiary amine as
ideal catalyst. We began investigating the reaction between 3-
(3-indolomethyl)oxindoles 1a and paraformaldehyde in the
7
67
8
79
9
DCE
-10
0
72
10
DCE
trace
presence of a chiral tertiary amine catalysts
3 followed by the
a Unless otherwise specified, the reactions were carried out on a 0.1 mmol
scale with 6 equiv (HCHO)n, 10 mol% cat. in 2 mL CH2Cl2 in the first step, then
added 1.2 equiv DABCO and 1.2 equiv NCS on a one-pot two steps manner.
b Isolated yield. c Determined by chiral HPLC.
addition of DABCO and NCS in different solvents (Table 1). To
our delight, chiral cyclohexanediamine based tertiary amine-
thiourea 3a catalyzed the reaction in CH2Cl2 delivered the
expected pentacyclic spirooxindole 2a in 72% yield with 91% ee
(Table 1, entry 1). Encouraged by the result, the more rigidity
catalyst 3b was used to promote the reaction. The reaction
exhibited in a slightly decrease in yield and enantioselectivity
and gave 2a in 64% yield with 88% ee (Table 1, entry 2). The
cinchona alkaloid derivatives (3c, 3d) were also evaluated and
gave lower enantioselectivity (Table 1, entries 3-4).
Subsequently, changing the solvent from CH2Cl2 to ClCH2CH2Cl
gave slightly higher enantioselectivity (Table 1, entry 5),
whereas CHCl3 and toluene resulted in a dramatic decrease in
yield and stereoselectivity (Table 1, entries 6-7). Lowering
Subsequently, we investigated the scope of 3-(3-
indolomethyl)oxindoles
Aldol/ chloroetherification/aromatization reaction using 3a (10
mol%) as the catalyst in ClCH2CH2Cl at 0 (Scheme 2). In general,
1 in the asymmetric one-pot stepwise
℃
the substrates bearing various functional groups (R), either an
electron-donating group or an electron-withdrawing on the
indole core were compatible with this reaction system,
affording the corresponding pentacyclic compounds with
moderate to good yields and excellent enantiocontrol (2b-2l, 2o,
51-72% yields, 87-96% ee), except for the 6-MeO and 7-Br
substituted substrates with a dramatic decrease in yields but
good enantioselectivities (2m and 2n, 15-38% yield, 93-95% ee).
It’s clear that the electronic features of the substituents on
indole ring had little effect on the enantioselectivities.
Furthermore, the substrates with various functional groups (R1)
on the oxindole core have also been investigated. When the
substituted groups of the oxindole N1 position were changed
from Boc to Ac, the corresponding products were obtained in
lower ee value (2p and 2q). In addition, Both the electron-
donating and electron-withdrawing substituents on the C4-C6
position of oxindole core were tolerated, providing the desired
products in excellent enantioselectivities (2r-2v, 92-94% ee),
while electron-withdrawing groups on C5-C6 position suffered
from low reaction efficiency in the first step (2t, 2v). According
to the experimental results, one can see that the electronic
features of the substituents (R1) on oxindole ring had little effect
on the enantioselectivities but great influence on reactivity,
probably due to the electron-withdrawing groups reduced the
nucleophilicity of enolate intermediate formed during the
reaction.
temperature to 0
℃ resulted in a better result with 95% ee
(Table 1, entry 8). Further lowering temperature did not
improve the enantioselectivity and the reaction became more
sluggish (Table 1, entry 9). The DABCO was vital to this reaction.
When the second step was proceeded without DABCO, no
obvious products were tested except much polarity
components under TLC analysis (Table 1, entry 10). The DABCO
might act as
chloroetherification process.
a
Lewis base and catalyst for the
Table 1. Optimization of the Reaction Conditions.
2 | J. Name., 2012, 00, 1-3
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To further expand the potential of this methodology, versatile
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transformations of the products into soDmOeI: 1o0t.h10e3r9/sCtr8uOcBt0u1r7a1l3lAy
diverse spirocyclic oxindoles were performed (Scheme 5). In
one-pot sequence, when adding 3 equivalents of NCS after the
Aldol procedure, substrates 1r could be readily transformed to
dearomatizated compound
4 in 76% yield and 94% ee.
Additionally, excellent diastereoselectivity was obtained
because of the steric hindrance of chlorine atom presented in
the substrate. Notably, the product 2a could undergo oxidative
rearrangement under NBS-HOAc-H2O-THF, affording the
product bispirooxindole
5
in moderate yield, high
enantioselectivity, and 1:1 dr. Furthermore, treatment the
product 2q with bulky p-nitrobenzene sulfonyl chloride in the
presence of trimethylamine and DMAP provided the product 6,
and the chemical structure of these pentacyclic spirooxindoles
2
has been confirmed by a single crystal X-ray analysis of 6.[11]
The only chiral quaternary carbon of pentacyclic spirooxindoles
was formation in the first Aldol reaction and were not change
2
in the subsequent process. So, the absolute configuration of the
chiral quaternary carbon has been confirmed by a single crystal
X-ray analysis of 1ra (the product of the first Aldol reaction of
1r).[12]
Scheme
3.
Substrate
Scope
for
One-pot
Stepwise
Aldol/Chloroetherification/Aromatization Reaction of
1
.
Scheme 5. Straightforward Transformations of Products to Other
Structurally Diverse Spirocyclic Oxindoles.
To examine the utility of the methodology, a gram scale
experiment was carried out under the optimized conditions. As
shown in Scheme 4, the reaction proceeded smoothly and
furnished 2a in good results, which are similarity to the results
of the original reaction illustrated in Table 1, entry 8.
Based on the aforementioned literatures, a plausible reaction
pathway is proposed in Scheme 6. Monomeric formaldehyde
was gradual released from its polymeric structure. Then the
chiral bifunctional thiourea catalyst was able to formally
transform
indolomethyl)oxindole
the
intermolecular
reaction
of
into
3-(3-
an
and
formaldehyde
intramolecular-like reaction due to their concurrently inducing
and activating nucleophiles (3-substituted oxindoles) and
electrophiles (formaldehyde) for excellent enantioselectivity.[9a]
subsequently, nucleophilic attack of the Aldol product to NCS
Scheme 4. Gram-Scale Experiment.
generated a chloronium ion
A
; then the DABCO might act as a
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Journal Name
Yu, H.-M. Liu, Eur. J. Med. Chem. 2015, 97, 673. (e) S. S. Panda,
R. A. Jones, P. Bachawala, P. P. MohaDpOaIt:r1a0,.1M03Vi9nie/iwC-RA8erOtivcB.le0M1O7n1eli3ndAe.
Chem. 2017, 17, 1515.
For selected examples, see: (a) M.-Z. Zhang, Q. Chen, G.-F.
Yang, Eur. J. Med. Chem. 2015, 89, 421. (b) T. P. Singh, O. M.
Singh, Mini-Rev. Med. Chem. 2018, 18, 9.
Lewis base, eliciting the cyclization to from a pyran ring in B.
finally, the aromatization occurred to afford 2 by release of HCl.
2
3
For selected examples, see: (a) H. Zheng, X. Liu, C. Xu, Y. Xia,
L. Lin, X. Feng, Angew. Chem. Int. Ed. 2015, 54, 10958. (b) N. J.
White, S. Pukrittayakamee, A. P. Phyo, R. Rueangweerayut, F.
Nosten, P. Jittamala, A. Jeeyapant, J. P. Jain, G. Lefèvre, R. Li,
B. Magnusson, T. T. Diagana, F. J. Leong, N. Engl. J. Med. 2014,
371, 403. (c) A. Lerchner, E. M. Carreira, J. Am. Chem. Soc.
2002, 124, 14826.
For selected examples, see: (a) B. Tan, G. Hernández-Torres,
C. F. Barbas, J. Am. Chem. Soc. 2011, 133, 12354. (b) Y. Liu, M.
Nappi, E. Arceo, S. Vera, P. Melchiorre, J. Am. Chem. Soc. 2011,
133, 15212. (c) W. Dai, H. Lu, X. Li, F. Shi, S.-J. Tu, Chem. Eur. J.
2014, 20, 11382. (d) J.-Q. Zhao, M.-Q. Zhou, Z.-J. Wu, Z.-H.
Wang, D.-F. Yue, X.-Y. Xu, X.-M. Zhang, W.-C. Yuan, Org. Lett.
2015, 17, 2238. (e) J.-Q. Zhao, Z.-J. Wu, M.-Q. Zhou, X.-Y. Xu,
X.-M. Zhang, W.-C. Yuan, Org. Lett. 2015, 17, 5020. (f) Y. Wang,
M.-S. Tu, L. Yin, M. Sun, F. Shi, J. Org. Chem. 2015, 80, 3223.
(g) F. Shi, R.-Y. Zhu, W. Dai, C.-S. Wang, S.-J. Tu, Chem. Eur. J.
2014, 20, 2597.
4
Scheme 6. Proposed Reaction Pathway.
Conclusions
5
Selected reviews for chiral catalytic asymmetric construction
of enantioenriched spirooxindoles, see: (a) J. E. M. N. Klein, R.
J. K. Taylor, Eur. J. Org. Chem. 2011, 2011, 6821. (b) N. R. Ball-
In summary, through the methodologies combination, we have
developed
chloroetherification/aromatization
indolomethyl)oxindoles to synthesis
spirooxindoles. With the combined protocol, a wide range of
enantioenriched polycyclic spirooxindoles, containing
a
catalytic
one-pot
sequential
Aldol/
of
3-(3-
Jones, J. J. Badilloa, A. K. Franz, Org. Biomol. Chem. 2012, 10
5165. (c) R. Rios, Chem. Soc. Rev. 2012, 41, 1060. (d) A. K.
Franz, N. V. Hanhan, N. R. Ball-Jones, ACS Catal. 2013, , 540.
(e) L. Hong, R. Wang, Adv. Synth. Catal. 2013, 355, 1023. (f) D.
Cheng, Y. Ishihara, B. Tan, C. F. Barbas III, ACS Catal. 2014,
743. (g) L.-J. Yan, Y.-C. Wang, ChemistrySelect 2016, , 6948.
,
of
pentacyclic
3
4
,
tetrahydropyrano[2,3-b]indole scaffold, could be smoothly
obtained with satisfactory results (up to 84% yield and 96% ee)
under mild conditions. Furthermore, the straightforward
transformations of the products into other structurally diverse
spirocyclic oxindoles were also feasible. Further application of
the new one-pot stepwise synthetic strategy in construction of
other complex natural products or pharmaceutically active
substances are in progress.
1
(h) G.-J. Mei, F. Shi, Chem. Commun. 2018, 54, 6607. Selected
examples for construction of enantioenriched spiro[pyran-3-
oxindole] scaffolds. see: (i) K. Zhao, Y. Zhi, T. Shu, A. Valkonen,
K. Rissanen, D. Enders, Angew. Chem. Int. Ed. 2016, 55, 12104.
(j) J.-L. Wu, B.-X. Du, Y.-C. Zhang, Y.-Y. He, J.-Y. Wang, P. Wu,
F. Shi, Adv. Synth. Catal. 2016, 358, 2777. (k) H.-W. Zhao, B. Li,
T. Tian, W. Meng, Z. Yang, X.-Q. Song, X.-Q. Chen, H.-L. Pang,
Eur. J. Org. Chem. 2015, 2015, 3320. (l) P. Kumari, S. Nandi, G.
Kumar, N. H. Khan, R. I. Kureshy, S. H. R. Abdi, E. Suresh, H. C.
Bajaj, RSC Adv. 2016, 6, 52384.
6
(a) D. S. Allgäuer, H. Mayr, Eur. J. Org. Chem. 2013, 2013, 6379.
(b) Z.-M. Yan, N. Wu, D. Liang, H.-S. Wang, Y.-M. Pan, Org. Lett.
2014, 16, 4048. (c) D. Srikrishna, P. K. Dubey, Tetrahedron Lett.
2014, 55, 6561. (d) D. Han, J. Chen, Q. He, R. H. Fan, Org. Lett.
2016, 18, 4690. (e) R. Kumar, M. Asthana, R. M. Singh, J. Org.
Conflicts of interest
There are no conflicts to declare.
Chem. 2017, 82
, 11531. (f) Y. Jiang, L. Deiana, R.
Acknowledgements
Alimohammadzadhe, L. Liu, J. Sun, A. Cordova, Eur. J. Org.
Chem. 2018, 2018, 1158.
7
8
For selected reviews, see: (a) F. Zhou, Y.-L. Liu, J. Zhou, Adv.
Synth. Catal. 2010, 352, 1381. (b) R. Dalpozzo, G. Bartolib, G.
Bencivenni, Chem. Soc. Rev. 2012, 41, 7247. (c) J.-R. Chen, X.-
Y. Yu, W.-J. Xiao, Synthesis 2015, 47, 604. (d) G. M. Zia-rania,
R. Moradia, N. Lashgari, Tetrahedron: Asymmetry 2015, 26
517. (e) R. Dalpozzo, Adv. Synth. Catal. 2017, 359, 1772.
For selected reviews and recent examples, see: (a) A. N. French,
S. Bissmire, T. Wirth, Chem. Soc. Rev. 2004, 33, 354. (b) U.
Hennecke, Chem. Asian J. 2012, 7, 456. (c) S. E. Denmark, W. E.
Kuester, M. T. Burk, Angew. Chem. Int. Ed. 2012, 51, 10938. (d) Y.
A. Cheng, W. Z. Yu, Y.-Y. Yeung, Org. Biomol. Chem. 2014, 12,
2333. (e) C. K. Tan, W. Z. Yu, Y.-Y. Yeung, Chirality, 2014, 26, 328.
(f) P. Zhou, Y. Cai, X. Zhong, W. Luo, T. Kang, J. Li, X. Liu, L. Lin, X.
Feng, ACS Catal. 2016, 6, 7778. (g) H. Wang, L. Huang, X. Cao, D.
Liang, A.-Y. Peng, Org. Biomol. Chem. 2017, 15, 7396. (h) Y.-C.
Chan, Y.-Y. Yeung, Angew. Chem. Int. Ed. 2018, 57, 3483. (i) N. S.
We gratefully acknowledge the financial support from the
National Natural Science Foundation of China (No. 21402132),
Science and Technology Department of Sichuan Province (No.
2016JY0228), Education Department of Sichuan Province (No.
16ZB0241), Sichuan University of Science & Engineering (No.
2014RC08). The China Postdoctoral Science Foundation (No.
2017M613000) and Sichuan Postdoctoral Science Foundation
are also greatly acknowledged for funding this work.
,
Notes and references
1
For selected reviews, see: (a) C. V. Galliford, K. A. Scheidt,
Angew. Chem. Int. Ed. 2007, 46, 8748. (b) B. M. Trost, M. K.
Brennan, Synthesis 2009, 3003. (c) N. Ye, H. Chen, E. A. Wold,
P.-Y. Shi, J. Zhou, ACS Infect. Dis. 2016, 2, 382. (d) B. Yu, D.-Q.
4 | J. Name., 2012, 00, 1-3
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COMMUNICATION
Marzijarani, R. Yousefi, A. Jaganathan, K. D. Ashtekar, J. E.
Jackson, B. Borhan, Chem. Sci. 2018, 9, 2898.
For selected examples, see: (a) X.-L. Liu, Y.-H. Liao, Z.-J. Wu, L.-
F. Cun, X.-M. Zhang, W.-C. Yuan, J. Org. Chem. 2010, 75, 4872.
(b) L. Cheng, L. Liu, H. Jia, D. Wang, Y.-J. Chen, J. Org. Chem.
2009, 74, 4650. (c) Z. Tang, Y. Shi, H. Mao, X. Zhu, W. Li, Y.
View Article Online
DOI: 10.1039/C8OB01713A
9
Cheng, W.-H. Zheng, C. Zhu, Org. Biomol. Chem. 2014, 12
6085. (d) X. Gao, J. Han, L. Wang, Org. Chem. Front. 2016,
,
,
3
656. (e) K. Shen, X. Liu, W. Wang, G. Wang, W. Cao, W. Li, X.
Hu, L. Lin, X. Feng, Chem. Sci. 2010, , 590.
1
10 For selected examples, see: (a) O. Lozano, G. Blessley, T. M.
Campo, A. L. Thompson, G. T. Giuffredi, M. Bettati, M. Walker,
R. Borman, V. Gouverneur, Angew. Chem. Int. Ed. 2011, 50
,
8105. (b) A. Jaganathan, A. Garzan, D. C. Whitehead, R. J.
Staples, B. Borhan, Angew. Chem. Int. Ed. 2011, 50, 2593. (c)
C. B. Tripathi, S. Mukherjee, Org. Lett. 2015, 17, 4424. (d) A.
Garzan, A. Jaganathan, N. S. Marzijarani, R. Yousefi, D. C.
Whitehead, J. E. Jackson, B. Borhan, Chem. Eur. J. 2013, 19
,
9015. (e) Y. A. Cheng, W. Z. Yu, Y.-Y. Yeung, Angew. Chem. Int.
Ed. 2015, 54, 12102. (f) Q. Yin, S.-L. You, Org. Lett. 2014, 16
,
2426.
11 CCDC-1822550 (6) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre.
12 CCDC-1822086 (1ra) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre.
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DOI: 10.1039/C8OB01713A
A general method for the synthesis of chiral pentacyclic spirooxindoles containing
tetrahydropyrano[2,3-b]indole scaffold through a one-pot stepwise sequence is reported.