Stereoselective Synthesis of Dispirooxindoles Incorporating Pyrrolo[2,1-a]isoquinoline via [3+2] Cycloaddition of Azomethine Ylides with a Thiazolo[3,2-a]indole Dipolarophile

Abstract

Highly regio- and stereoselective synthesis of dispiropyrrolo[2,1-a]isoquinoline-oxindoles have been developed by the one-pot three component reaction of isatins, 1,2,3,4-tetrahydroisoquinoline (THIQ), and a thiazolo[3,2-a]indole derivative. The reaction proceeds regioselectively through an exo-Re face approach of the in situ generated tetrahydroisoquinolium ylides towards the dipolarophile yielding the corresponding [3+2] cycloadducts in excellent yields and stereoselectivity.

Key words

[3+2] cycloaddition - azomethine ylide - 1,2,3,4-tetrahydroisoquinoline - thiazolo[3,2-a]indole - spiropyrrolo[2,1-a]isoquinoline

• References

• 1 Breugst M, Reissig H.-U. Angew. Chem. Int. Ed. 2020; 59: 12293 ; and references cited therein
• 2 Michael JP. Nat. Prod. Rep. 2005; 22: 603
• 3 Liddell JR. Nat. Prod. Rep. 2001; 18: 441
• 4 Saraswat P, Jeyabalan G, Hassan MZ, Rahman MU, Nyola NK. Synth. Commun. 2016; 46: 1643
• 5 Döndas HA, Retamosa MG, Sansano JM. Synthesis 2017; 49: 2819
• 6 Bdiri B, Zhao B.-J, Zhou Z.-M. Tetrahedron: Asymmetry 2017; 28: 876
• 7 Meyer AG, Ryan JH. Molecules 2016; 21: 935
• 8 Najera C, Sansano JM. Curr. Org. Chem. 2003; 7: 1105
• 9 Saoussen H, Boudriga S, Porzio F, Soldera A, Askri M, Knorr M, Rousselin Y, Kubicki MM, Golz C, Strohmann C. J. Org. Chem. 2015; 80: 9064
• 10 Filatov AS, Knyazev NA, Shmakov SV, Bogdanov AA, Ryazantsev MN, Shtyrov AA, Starova GL, Molchanov AP, Larina AG, Boitsov VM, Stepakov AV. Synthesis 2019; 51: 713
• 11 Filatov AS, Wang S, Khoroshilova OV, Lozovskiy SV, Larina AG, Boitsov VM, Stepakov AV. J. Org. Chem. 2019; 84: 7017
• 12 Barkov AY, Zimnitskiy NS, Korotaev VY, Kutyashev IB, Moshkin VS, Sosnovskikh VY. Chem. Heterocycl. Compd. (Engl. Transl.) 2017; 53: 451
• 13 Ardill H, Grigg R, Sridharan V, Surendrakumar S, Thianpatanagul S, Kanajun S. J. Chem. Soc., Chem. Commun. 1986; 602
• 14 Pässler U, Knölker H.-J. The Pyrrolo[2,1-a]isoquinoline Alkaloids . In The Alkaloids: Chemistry and Biology, Vol. 70. Knölker H.-J. Elsevier; Amsterdam: 2011: 79-151
• 15 Shi R.-G, Sun J, Yan C.-G. ACS Omega 2017; 2: 7820 ; and references cited therein
• 16 Zhang Q, Tu G, Zhao Y, Cheng T. Tetrahedron 2002; 58: 6795
• 17 Wang RF, Yang XW, Ma CM, Cai SQ, Li JN, Shoyama Y. Heterocycles 2004; 63: 1443
• 18 Xiang L, Xing D, Wang W, Wang R, Ding Y, Du L. Phytochemistry 2005; 66: 2595
• 19 Xiang Y, Li Y, Zhang J, Li P, Yao Y. Yaoxue Xuebao 2007; 42: 618
• 20 Andersen RJ, Faulkner DJ, He CH, Van Duyne GD, Clardy J. J. Am. Chem. Soc. 1985; 107: 5492
• 21 Sathi V, Thomas NV, Deepthi A. Org. Biomol. Chem. 2020; 18: 7822
• 22 Berg R, Bergman J. Tetrahedron 2017; 73: 5654
• 23 Thomas NV, Sathi V, Deepthi A, Leena SS, Chopra S. J. Heterocycl. Chem. 2021; 58: 48
• 24 Huang Y, Huang YX, Sun J, Yan CG. RSC Adv. 2018; 8: 23990
• 25 Boudriga S, Haddad S, Askri M, Soldera A, Knorr M, Strohmannd C, Golz C. RSC Adv. 2019; 9: 11082
• 26 Toumi A, Boudriga S, Hamden K, Daoud I, Askri M, Soldera A, Lohier JF, Strohmann C, Brieger L, Knorr M. J. Org. Chem. 2021; 86: 13420
• 27 CCDC 2128145 (6b) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 28a The cycloadduct initially formed probably undergoes a transesterification in MeOH promoted by the secondary amine 4.
• 28b See also: Otera J. Chem. Rev. 1993; 93: 1449
• 29 The cycloaddition of substrates (i) 3b in EtOH, (ii) 3c in PrOH, and (iii) 3d in i-PrOH resulted in the formation of compounds 6n, 6o, and 6p, respectively. In the case of 6n and 6o, transesterification took place for ester group attached to pyrrolidine ring while this was not observed during the formation of 6p.
• 30 Xu Y.-W, Wang J, Wang G, Zhen L. J. Org. Chem. 2021; 86: 91