Organocatalytic Regioselective [3+2] Annulation of Morita-Baylis-Hillman Carbonates with Azonaphthalenes: An Efficient Access to 3-Spiropyrazole- 2-oxindoles

Author(s): Yuyu Cheng, Zhongyue Lu, Pengfei Li*

Journal Name: Current Organocatalysis

Volume 7 , Issue 2 , 2020

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Graphical Abstract:


Background: A cheap and commercially available organocatalyst, 4-dimethylaminopyridine was successfully employed in the regioselective [3+2] cycloaddition of isatin-derived Morita-Baylis- Hillman carbonates with azonaphthalenes for the construction of 3-spiropyrazole-2-oxindoles in excellent yields under mild conditions.

Methods: In the presence of 4-dimethylaminopyridine with a loading of 10 mol%, a series of isatinderived Morita-Baylis-Hillman carbonates reacted smoothly with azonaphthalenes in dichloromethane at room temperature to furnish 3-spiropyrazole-2-oxindoles in 72-98% yield.

Results and Conclusion: In summary, we have developed reasonably cheap and commercially available 4-dimethylaminopyridine-mediated regioselective [3+2] annulations between isatin-derived Morita- Baylis-Hillman carbonates and azonaphthalenes for the construction of 3-spiropyrazole-2-oxindoles under mild conditions.

Keywords: Annulation, azonaphthalenes, MBH carbonates, 4-dimethylaminopyridine, regioselective, spirooxindole.

Galliford, C.V.; Scheidt, K.A. Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents. Angew. Chem. Int. Ed. Engl., 2007, 46(46), 8748-8758.
[] [PMID: 17943924]
Yu, B.; Yu, Z.; Qi, P-P.; Yu, D-Q.; Liu, H-M. Discovery of orally active anticancer candidate CFI-400945 derived from biologically promising spirooxindoles: success and challenges. Eur. J. Med. Chem., 2015, 95, 35-40.
[] [PMID: 25791677]
Yu, B.; Yu, D-Q.; Liu, H-M. Spirooxindoles: Promising scaffolds for anticancer agents. Eur. J. Med. Chem., 2015, 97, 673-698.
[] [PMID: 24994707]
Zhou, F.; Liu, Y-L.; Zhou, J. Catalytic asymmetric synthesis of oxindoles bearing a tetrasubstituted stereocenter at the C-3 position. Adv. Synth. Catal., 2010, 352, 1381-1407.
Singh, G.S.; Desta, Z.Y. Isatins as privileged molecules in design and synthesis of spiro-fused cyclic frameworks. Chem. Rev., 2012, 112(11), 6104-6155.
[] [PMID: 22950860]
Dalpozzo, R.; Bartoli, G.; Bencivenni, G. Recent advances in organocatalytic methods for the synthesis of disubstituted 2- and 3-indolinones. Chem. Soc. Rev., 2012, 41(21), 7247-7290.
[] [PMID: 22899437]
Ball-Jones, N.R.; Badillo, J.J.; Franz, A.K. Strategies for the enantioselective synthesis of spirooxindoles. Org. Biomol. Chem., 2012, 10(27), 5165-5181.
[] [PMID: 22581310]
Liu, Y.; Wang, H.; Wan, J. Recent advances in diversity oriented synthesis through isatin-based multicomponent reactions. Asian J. Org. Chem., 2013, 2, 374-386.
Hong, L.; Wang, R. Recent advances in asymmetric organocatalytic construction of 3,3′-spirocyclic oxindoles. Adv. Synth. Catal., 2013, 355, 1023-1052.
Santos, M.M.M. Recent advances in the synthesis of biologically active spirooxindoles. Tetrahedron, 2014, 70, 9735-9757.
Cheng, D.; Ishihara, Y.; Tan, B.; Barbas, C.F. III Organocatalytic asymmetric assembly reactions: synthesis of spirooxindoles via organocascade strategies. ACS Catal., 2014, 4, 743-762.
Wu, H.; He, Y-P.; Shi, F. Recent advances in chiral phosphoric acid catalyzed asymmetric reactions for the synthesis of enantiopure indole derivatives. Synthesis, 2015, 47, 1990-2016.
Chen, D-Z.; Xiao, W-J.; Chen, J-R. Synthesis of spiropyrazoline oxindoles by a formal [4 + 1] annulation reaction between 3-bromooxindoles and in situ-derived 1,2-diaza-1,3-dienes. Org. Chem. Front., 2017, 4, 1289-1293.
Selvakumar, K.; Vaithiyanathan, V.; Shanmugam, P. An efficient stereoselective synthesis of 3-spirocyclopentene- and 3-spiropyrazole-2-oxindoles via 1,3-dipolar cycloaddition reaction. Chem. Commun. (Camb.), 2010, 46(16), 2826-2828.
[] [PMID: 20369196]
Singh, S.; Saquib, M.; Singh, S.B.; Singh, M.; Singh, J. Catalyst free, multicomponent-tandem synthesis of spirooxindole-indazolones and spirooxindolepyrazolines: a glycerol mediated green approach. RSC Advances, 2015, 5, 45152-45157.
Peng, J.; Huang, X.; Jiang, L.; Cui, H-L.; Chen, Y-C. Tertiary amine-catalyzed chemoselective and asymmetric [3 + 2] annulation of Morita-Baylis-Hillman carbonates of isatins with propargyl sulfones. Org. Lett., 2011, 13(17), 4584-4587.
[] [PMID: 21815615]
Wei, F.; Huang, H-Y.; Zhong, N-J.; Gu, C-L.; Wang, D.; Liu, L. Highly enantioselective [3 + 2]-annulation of isatin-derived morita-baylis-hillman adducts with cyclic sulfonimines. Org. Lett., 2015, 17(7), 1688-1691.
[] [PMID: 25781216]
Zhao, Y-Y.; Zhao, S.; Xie, J-K.; Hu, X-Q.; Xu, P-F. Synthesis of spirocyclic oxindole dihydrothiophenes by DBU-catalyzed [3+2] annulation of Morita-Baylis-Hillman carbonates with isothiocyanates. J. Org. Chem., 2016, 81(21), 10532-10537.
[] [PMID: 27649297]
Fan, X.; Yang, H.; Shi, M. Tertiary amine-catalyzed difluoromethylthiolation of Morita-Baylis-Hillman carbonates of isatins with Zard’s trifluoromethylthiolation reagent. Adv. Synth. Catal., 2017, 359, 49-57.
Ren, Y.; Meng, L-G.; Peng, T.; Zhu, L.; Wang, L. Cycloaddition of isatin-derived Morita-Baylis-Hillman adducts with azo esters: a simple protocol to access 3-spiropyrazole-2-oxindoles. Adv. Synth. Catal., 2018, 360, 3176-3180.
Qi, L-W.; Li, S.; Xiang, S-H.; Wang, J.; Tan, B. Asymmetric construction of atropisomeric biaryls via a redox neutral cross-coupling strategy. Nat. Catal., 2019, 2, 314-323.
Yuan, H.; Li, Y.; Zhao, H.; Yang, Z.; Li, X.; Li, W. Asymmetric synthesis of atropisomeric pyrazole via an enantioselective reaction of azonaphthalene with pyrazolone. Chem. Commun. (Camb.), 2019, 55(84), 12715-12718.
[] [PMID: 31588462]
Qi, L-W.; Mao, J-H.; Zhang, J.; Tan, B. Organocatalytic asymmetric arylation of indoles enabled by azo groups. Nat. Chem., 2018, 10(1), 58-64.
[] [PMID: 29256504]
Hu, Y-L.; Wang, Z.; Yang, H.; Chen, J.; Wu, Z-B.; Lei, Y.; Zhou, L. Conversion of two stereocenters to one or two chiral axes: atroposelective synthesis of 2,3-diarylbenzoindoles. Chem. Sci. (Camb.), 2019, 10(28), 6777-6784.
[] [PMID: 31391898]
Zhao, H.; Yuan, H.; Zhang, Y.; Li, R.; Li, W. Enamine catalytic annulation of azonaphthalenes: an access to indole derivatives. Org. Lett., 2019, 21(16), 6557-6561.
[] [PMID: 31353910]
Cheng, Y.; Han, Y.; Li, P. Organocatalytic enantioselective [1+4] annulation of Morita-Baylis-Hillman carbonates with electron-deficient olefins: access to chiral 2,3-dihydrofuran derivatives. Org. Lett., 2017, 19(18), 4774-4777.
[] [PMID: 28846432]
Cheng, Y.; Fang, Z.; Li, W.; Li, P. Phosphine-mediated enantioselective [4+1] annulations between ortho-quinone methides and Morita–Baylis–Hillman carbonates. Org. Chem. Front., 2018, 5, 2728-2733.
Wang, T.; Zhang, P.; Li, W.; Li, P. Phosphine-mediated enantioselective [1+4] annulations of Morita-Baylis-Hillman carbonates with 2-enoylpyridines. RSC Advances, 2018, 8, 41620-41623.
Qian, C.; Zhang, P.; Li, W.; Li, P. Phosphine-catalyzed enantioselective [1+4] annulation of Morita-Baylis-Hillman carbonates with α,β-unsaturated imines. Asian J. Org. Chem., 2019, 8, 242-245.
Zhang, P.; Guo, X.; Liu, C.; Li, W.; Li, P. Enantioselective construction of pyridine N-oxides featuring 2,3-dihydrofuran motifs via phosphine-catalyzed [4+1]-annulation of 2-enoylpyridine N-oxides with Morita-Baylis-Hillman carbonates. Org. Lett., 2019, 21(1), 152-155.
[] [PMID: 30574783]
Xie, P.; Huang, Y. Morita-Baylis-Hillman adduct derivatives (MBHADs): versatile reactivity in Lewis base-promoted annulation. Org. Biomol. Chem., 2015, 13(32), 8578-8595.
[] [PMID: 26133693]

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Article Details

Year: 2020
Published on: 01 July, 2020
Page: [134 - 139]
Pages: 6
DOI: 10.2174/2213337206666191125094216
Price: $25

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