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DOI: 10.1055/a-2605-1321
8-Aminoimidazo[1,2-a]pyridine-Directed Nickel-Catalyzed β-C(sp 2)–H Arylation and Alkylation: Implementation for Late-Stage C–H Activation towards Biologically Relevant Compounds

Abstract
We herein report an efficient and convenient protocol for the Ni(II)-catalyzed ortho-C(sp 2)–H arylation as well as alkylation using 8-aminoimidazo[1,2-a]pyridine (8-AIP) as a unique directing group in the absence of any external ligand and oxidant. This protocol is scalable, has excellent yield, exhibits high levels of β-site selectivity, and tolerates a broad spectrum of functional groups. A kinetic study was also undertaken to establish a plausible reaction pathway. Single-crystal XRD analysis was carried out to determine one of the structures. Furthermore, late-stage functionalization of the synthesized derivatives demonstrates the methodology’s synthetic adaptability and showcases the use of 8-AIP as an inbuilt directing group.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2605-1321.
- Supporting Information
Publication History
Received: 02 April 2025
Accepted after revision: 09 May 2025
Accepted Manuscript online:
09 May 2025
Article published online:
11 June 2025
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References
- 1a Chen Z, Wang B, Zhang J, Yu W, Liu Z, Zhang Y. Org. Chem. Front. 2015; 2: 1107
- 1b Sambiagio C, Schönbauer D, Blieck R, Dao-Huy T, Pototsching G, Schaaf P, Wiensinger T, Zia MF, Wencel-Delord J, Besset T, Maes BU. W, Schnürch M. Chem. Soc. Rev. 2018; 47: 6603
- 1c Rao W.-H, Shi B.-F. Org. Chem. Front. 2016; 3: 1028
- 1d Chen F.-J, Liao G, Li X, Wu J, Shi B.-F. Org. Lett. 2014; 16: 5644
- 1e Yin X.-S, Li Y.-C, Yuan J, Gu W.-J, Shi B.-F. Org. Chem. Front. 2015; 2: 115
- 1f Zhao S, Liu Y.-J, Yan S.-Y, Chen F.-J, Zhang Z.-Z, Shi B.-F. Org. Lett. 2015; 17: 3338
- 1g Rao W.-H, Shi B.-F. Org. Lett. 2015; 17: 2784
- 1h Li Y, Liu Y.-J, Shi B.-F. Adv. Synth. Catal. 2017; 359: 4117
- 2a Wencel-Delord J, Dröge T, Liu F, Glorius F. Chem. Soc. Rev. 2011; 40: 4740
- 2b Kuhl N, Hopkinson MN, Wencel-Delord J, Glorius F. Angew. Chem. Int. Ed. 2012; 51: 10236
- 2c Hartwig JF, Larsen MA. ACS Cent. Sci. 2016; 2: 281
- 2d Gensch T, Hopkinson MN, Glorius F, Wencel-Delord J. Chem. Soc. Rev. 2016; 45: 2900
- 2e Santoro S, Ferlin F, Luciani L, Ackermann L, Vaccaro L. Green Chem. 2017; 19: 1601
- 2f Gensch T, James MJ. M. J, Dalton T, Glorius F. Angew. Chem. Int. Ed. 2018; 57: 2296
- 2g Meyer TH, Finger LH, Gandeepan P, Ackermann L. Trends Chem. 2019; 1: 63
- 2h Gandeepan P, Kaplaneris N, Santoro S, Vaccaro L, Ackermann L. ACS Sustainable Chem. Eng. 2019; 7: 8023
- 2i Gandeepan P, Müller T, Zell D, Cera G, Warratz S, Ackermann L. Chem. Rev. 2019; 119: 2192
- 2j Yu C, Sanjosé-Orduna J, Patureau FW, Pérez-Temprano MH. Chem. Soc. Rev. 2020; 49: 1643
- 2k Gandeepan P, Finger LH, Meyer TH, Ackermann L. Chem. Soc. Rev. 2020; 49: 4254
- 3a Daugulis O, Roane J, Tran LD. Acc. Chem. Res. 2015; 48: 1053
- 3b Rouquet G, Chatani N. Angew. Chem. Int. Ed. 2013; 52: 11726
- 3c Rej S, Ano Y, Chatani N. Chem. Rev. 2020; 120: 1788
- 3d Roane J, Daugulis O. J. Am. Chem. Soc. 2016; 138: 4601
- 4a Guo X.-X, Gu D.-W, Wu Z, Zhang W. Chem. Rev. 2015; 115: 1622
- 4b Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
- 4c Li S, Qin L, Dong L. Org. Biomol. Chem. 2016; 14: 4554
- 4d Arockiam PB, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879
- 4e Pan S, Shibata T. ACS Catal. 2013; 3: 704
- 5 Genchi G, Carocci A, Lauria G, Stefania M, Catalano SA. Int. J. Environ. Res. Public Health 2020; 17: 679
- 6a Yamaguchi J, Muto K, Itami K. Eur. J. Org. Chem. 2013; 1: 19
- 6b Harry NA, Saranya S, Ujwaldev SM, Anilkumar G. Catal. Sci. Technol. 2019; 9: 1726
- 7a Hachiya H, Hirano K, Satoh T, Miura M. Org. Lett. 2009; 11: 1737
- 7b Canivet J, Yamaguchi J, Ban I, Itami K. Org. Lett. 2009; 11: 1733
- 8a Aihara Y, Chatani N. J. Am. Chem. Soc. 2013; 135: 5308
- 8b Honeycutt AP, Hoover JM. ACS catal. 2017; 7: 4597
- 9 Yokota A, Aihara Y, Chatani N. J. Org. Chem. 2014; 79: 11922
- 10a Zhao S, Liu B, Zhan BB, Zhang WD, Shi BF. Org. Lett. 2016; 18: 4586
- 10b Liu B, Zhang ZZ, Li X, Shi BF. Org. Chem. Front. 2016; 3: 897
- 11a Mondal B, Ghosh P, Kundu MK, Das TK, Das S. Org. Biomol. Chem. 2021; 19: 360
- 11b Mondal B, Ghosh P, Kundu MK, Das S. Org. Biomol. Chem. 2021; 19: 1604
- 11c Hajra AK, Ghosh P, Roy C, Kundu M, Ghosh S, Das S. Org. Biomol. Chem. 2024; 22: 6617
- 12 Garamvölgyi R, Dobos J, Sipos A, Boros S, Illyés E, Baska F, Kékesi L, Szabadkai I, Szantai-Kis C, Kéri G, Őrfi L. Eur. J. Med. Chem. 2016; 108: 623
- 13 Hamaguchi W, Koganemaru Y, Sekiyoka R, Kaneko O, Kato K. PCT Int. Appl 2012108490, 2012
- 14 Liscio P, Carotti A, Asciutti S, Karlberg T, Bellocchi D, Macchiarulo LL. A, Aaronson SA, Schüler H, Pellicciari R, Camaioni E. J. Med. Chem. 2014; 57: 2807
- 15 Blair VL, Carrella LM, Clegg W, Conway B, Harrington RW, Hogg LM, Klett J, Mulvey RE, Rentschler E, Russo L. Angew. Chem. Int. Ed. 2008; 47: 6208
- 16a Bergman RG. Nature 2007; 446: 391
- 16b Hong B, Luo T, Lei X. ACS Cent. Sci. 2020; 6: 622
- 16c Moir M, Danon JJ, Reekie TA, Kassiou M. Expert Opin. Drug Discov. 2019; 14: 1137
- 16d Guillemard L, Kaplaneris N, Ackermann L, Johansson MJ. Nat. Rev. Chem. 2021; 5: 522
- 16e Castellino NJ, Montgomery AP, Danon JJ, Kassiou M. Chem. Rev. 2023; 123: 8127
- 17 Garamvolgyi R, Dobos J, Sipos A, Boros S, Illyes E, Baska F, Kekesi L, Szabadkai I, Szantai-Kis C, Keri G, Orfi L. Eur. J. Med. Chem. 2016; 108: 623
For a recent review of Ni-catalyzed C–H bond functionalization, see: