Regioselective C-H Sulfenylation of -sulfonyl Protected 7-azaindoles Promoted by TBAI: a Rapid Synthesis of 3-thio-7-azaindoles

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 May 6

PMID 35518137

Authors

Jingyan Hu

Xiaoming Ji

Shuai Hao

Mingqin Zhao

Miao Lai

Tianbao Ren

Gaolei Xi

Erbin Wang

Juanjuan Wang

Zhiyong Wu

Affiliations

Soon will be listed here.

Abstract

This paper describes the regioselective C-3 sulfenylation of -sulfonyl protected 7-azaindoles with sulfonyl chlorides. In this transformation, dual roles of TBAI serving as both promoter and desulfonylation reagent have been demonstrated. The reaction proceeded smoothly under simple conditions to afford 3-thio-7-azaindoles in moderate to good yields with broad substrate scopes. This protocol refrains from using transition-metal catalysts, strong oxidants or bases, and shows its practical synthetic value in organic synthesis.

Citing Articles

Novel 4-alkoxy Meriolin Congeners Potently Induce Apoptosis in Leukemia and Lymphoma Cells.

Krings K, Wassenberg T, Cea-Medina P, Schmitt L, Lechtenberg I, Llewellyn T Molecules. 2025; 29(24.

PMID: 39770138 PMC: 11676355. DOI: 10.3390/molecules29246050.

Pushing Boundaries: What's Next in Metal-Free C-H Functionalization for Sulfenylation?.

Rani P, Chahal S, Singh R, Sindhu J Top Curr Chem (Cham). 2024; 382(2):13.

PMID: 38607428 DOI: 10.1007/s41061-024-00460-1.

References

Irie T, Sawa M . 7-Azaindole: A Versatile Scaffold for Developing Kinase Inhibitors. Chem Pharm Bull (Tokyo). 2018; 66(1):29-36. DOI: 10.1248/cpb.c17-00380. View

Hong S, Kim J, Seo J, Jung K, Hong S, Hong S . Design, synthesis, and evaluation of 3,5-disubstituted 7-azaindoles as Trk inhibitors with anticancer and antiangiogenic activities. J Med Chem. 2012; 55(11):5337-49. DOI: 10.1021/jm3002982. View

Liu S, Yang H, Jiao L, Zhang J, Zhao C, Ma Y . Regioselective deoxygenative chalcogenation of 7-azindole N-oxides promoted by I/PEG-200. Org Biomol Chem. 2019; 17(47):10073-10087. DOI: 10.1039/c9ob02044f. View

Wu Y, Huang H, Shen J, Tseng H, Ho J, Chen Y . Water-catalyzed excited-state proton-transfer reactions in 7-azaindole and its analogues. J Phys Chem B. 2014; 119(6):2302-9. DOI: 10.1021/jp506136v. View

Kannaboina P, Kumar K, Das P . Site-Selective Intermolecular Oxidative C-3 Alkenylation of 7-Azaindoles at Room Temperature. Org Lett. 2016; 18(5):900-3. DOI: 10.1021/acs.orglett.5b03429. View

Chen X, Jin Z, Gong Y, Zhao N, Wang X, Ran Y . 5-HT receptor agonist and memory-enhancing properties of hypidone hydrochloride (YL-0919), a novel 5-HT receptor partial agonist and SSRI. Neuropharmacology. 2018; 138:1-9. DOI: 10.1016/j.neuropharm.2018.05.027. View

Zhang M, Chen Q, Yang G . A review on recent developments of indole-containing antiviral agents. Eur J Med Chem. 2014; 89:421-41. PMC: 7115707. DOI: 10.1016/j.ejmech.2014.10.065. View

Song J, Reeves J, Gallou F, Tan Z, Yee N, Senanayake C . Organometallic methods for the synthesis and functionalization of azaindoles. Chem Soc Rev. 2007; 36(7):1120-32. DOI: 10.1039/b607868k. View

Zhang J, Wang Z, Chen L, Liu Y, Liu P, Dai B . The fast and efficient KI/HO mediated 2-sulfonylation of indoles and -methylpyrrole in water. RSC Adv. 2022; 8(72):41651-41656. PMC: 9092009. DOI: 10.1039/c8ra09367a. View

10.

Xiao F, Chen H, Xie H, Chen S, Yang L, Deng G . Iodine-catalyzed regioselective 2-sulfonylation of indoles with sodium sulfinates. Org Lett. 2013; 16(1):50-3. DOI: 10.1021/ol402987u. View

11.

Lane B, Brown M, Sames D . Direct palladium-catalyzed C-2 and C-3 arylation of indoles: a mechanistic rationale for regioselectivity. J Am Chem Soc. 2005; 127(22):8050-7. DOI: 10.1021/ja043273t. View

12.

Chen L, Zou Y . Recent progress in the synthesis of phosphorus-containing indole derivatives. Org Biomol Chem. 2018; 16(41):7544-7556. DOI: 10.1039/c8ob02100g. View

13.

Alves F, Barreiro E, Fraga C . From nature to drug discovery: the indole scaffold as a 'privileged structure'. Mini Rev Med Chem. 2009; 9(7):782-93. DOI: 10.2174/138955709788452649. View

14.

Potavathri S, Pereira K, Gorelsky S, Pike A, LeBris A, DeBoef B . Regioselective oxidative arylation of indoles bearing N-alkyl protecting groups: dual C-H functionalization via a concerted metalation-deprotonation mechanism. J Am Chem Soc. 2010; 132(41):14676-81. PMC: 2954267. DOI: 10.1021/ja107159b. View

15.

Kannaboina P, Anilkumar K, Aravinda S, Vishwakarma R, Das P . Direct C-2 arylation of 7-azaindoles: chemoselective access to multiarylated derivatives. Org Lett. 2013; 15(22):5718-21. DOI: 10.1021/ol4027478. View

16.

Lane B, Sames D . Direct C-H bond arylation: selective palladium-catalyzed C2-arylation of N-substituted indoles. Org Lett. 2004; 6(17):2897-900. DOI: 10.1021/ol0490072. View

17.

Gerhauser C, You M, Liu J, Moriarty R, Hawthorne M, Mehta R . Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes. Cancer Res. 1997; 57(2):272-8. View

18.

Wu Z, Song H, Cui X, Pi C, Du W, Wu Y . Sulfonylation of quinoline N-oxides with aryl sulfonyl chlorides via copper-catalyzed C-H bonds activation. Org Lett. 2013; 15(6):1270-3. DOI: 10.1021/ol400178k. View

19.

Equbal D, Singh R, Saima , Lavekar A, Sinha A . Synergistic Dual Role of [hmim]Br-ArSOCl in Cascade Sulfenylation-Halogenation of Indole: Mechanistic Insight into Regioselective C-S and C-S/C-X (X = Cl and Br) Bond Formation in One Pot. J Org Chem. 2019; 84(5):2660-2675. DOI: 10.1021/acs.joc.8b03097. View

20.

Zhao S, Wang S . Luminescence and reactivity of 7-azaindole derivatives and complexes. Chem Soc Rev. 2010; 39(8):3142-56. DOI: 10.1039/c001897j. View