Copper Promoted 8-Aminoimidazo[1,2-a]pyridine-Directed Additive-Free Ortho C(sp2)–H C–S, C–Se Functionalization of (Hetero)Arenes

Priyadarshi Manna; Rusmita Mukherjee; Mrinalkanti Kundu; Susanta Sekhar Adhikari

doi:10.1055/a-2755-9816

Synthesis, Table of Contents

Synthesis
DOI: 10.1055/a-2755-9816

Feature

Copper Promoted 8-Aminoimidazo[1,2-a]pyridine-Directed Additive-Free Ortho C(sp²)–H C–S, C–Se Functionalization of (Hetero)Arenes

Authors

Priyadarshi Manna

¹Chemistry, TCG Lifesciences Private Limited, Kolkata, India (Ringgold ID: RIN30151)

²Department of Chemistry, University of Calcutta, Kolkata, India (Ringgold ID: RIN210244)
Rusmita Mukherjee

¹Chemistry, TCG Lifesciences Private Limited, Kolkata, India (Ringgold ID: RIN30151)
Mrinalkanti Kundu

¹Chemistry, TCG Lifesciences Private Limited, Kolkata, India (Ringgold ID: RIN30151)
Susanta Sekhar Adhikari

²Department of Chemistry, University of Calcutta, Kolkata, India (Ringgold ID: RIN210244)

Abstract

All articles of this category

Abstract

Diaryl sulfides, diaryl selenides, and their derivatives are crucial scaffolds in the fields of organic chemistry and drug discovery. We report a practical and broadly applicable strategy for additive-free copper(II)-catalyzed ortho-sulfanylation and selanylation of β-C(sp²)–H bonds in (hetero)arenes, directed by 8-aminoimidazo[1,2-a]pyridine (8-AIP), a removable 6,5-fused bicyclic N,N-bidentate directing group. This protocol features mild reaction conditions that enable the formation of diverse functionalized thioethers and selenides using thiols, disulfides, and diselenides, with enhanced functional group tolerance and unique site-selectivity. The present protocol is reproducible in gram scale, and, in addition, we have also the showed cleavage of chelating auxiliary.

Keywords

C–H activation - ß-C(sp²)–H thiolation & selanylation - Additive free - Cu-catalysis - 8-AIP - Late-stage functionalization

Full Text

References

References

1a Feng MH, Tang BQ, Liang SH, Jiang XF. Curr Top Med Chem 2016; 16: 1200
1b Devendar P, Yang G-F. Top Curr Chem 2017; 375: 82
1c Woods JA, Hadfield JA, McGown AT, Fox BW. Bioorg Med Chem 1993; 1: 333
1d Engman L, Cotgreave I, Angulo M, Taylor CW, PaineMurrieta GD, Powis G. Anticancer Res 1997; 17: 4599-4605
1e La Regina G, Edler MC, Brancale A. et al. J Med Chem 2007; 50: 2865-2874
1f Dunbar KL, Scharf DH, Litomska A, Hertweck C. Chem Rev 2017; 117: 5521-5577
1g Dvorak CA, Schmitz WD, Poon DJ. et al. Angew Chem Int Ed 2000; 39: 1664-1666
1h Dvorak CA, Schmitz WD, Poon DJ. et al. Angew Chem 2000; 112: 1730-1732
1i Moreno E, Plano D, Lamberto I. et al. Eur J Med Chem 2012; 47: 283-298
1j Alcaraz M-L, Atkinson S, Cornwall P. et al. Org Process Res Dev 2005; 9: 555-569
1k Grädler U, Czodrowski P, Tsaklakidis C. et al. Bioorg Med Chem Lett 2014; 24: 4141-4150
1l Kalgutkar AS, Kozak KR, Crews BC, Hochgesang GP, Marnett LJ. J Med Chem 1998; 41 (24) 4800-4818

2a McGrath NA, Brichacek M, Njardarson JT. J Chem Educ 2010; 87: 1348-1349
2b Ilardi EA, Vitaku E, Njardarson JT. J Med Chem 2014; 57: 2832
2c https://njardarson.lab.arizona.edu/content/top-pharmaceuticals-poster
2d Benedetto Tiz D, Rosati O, Sancineto L. Phosphorus Sulfur Silicon Relat Elem 2025; 1-39

3a Zhang Z-X, Willis MC. Trends Chem 2023; 5: 3-6
3b Das S, Dhibar A, Sahoo B. ACS Org Inorg Au 2025; 5: 1-12

4a Woods JA, Hadfield JA, McGown AT, Fox BW. Bioorg Med Chem 1993; 1: 333
4b Engman L, Stern D, Frisell H. et al. Bioorg Med Chem 1995; 3: 1255
4c Chatterjee T, Ranu BC. J Org Chem 2013; 78: 7145
4d De Aquino Silva D, Silva MRP, Guerra GP, do Sacramento M, Alves D, Prigol M. Comp Biochem Physiol C: Toxicol Pharmacol 2021; 239: 108892
4e Reich HJ, Hondal RJ. ACS Chem Biol 2016; 11: 821-841
4f Rodriguez CG, Rodriguez JB. ChemMedChem 2024; 19: e202400063
4g Nogueira CW, Zeni G, Rocha JBT. Chem Rev 2004; 104 (12) 6255-6286

5a Lou Z, Li P, Han K. Acc Chem Res 2015; 48: 1358-1368
5b Manjare ST, Kim Y, Churchill DG. Acc ChemRes 2014; 47: 2985-2998
5c Tang B, Yin L, Wang X, Chen Z, Tong L, Xu K. Chem Commun 2009; 5293-5295

6a Sonoda N, Yamamoto G, Natsukawa K, Kondo K, Murai S. Tetrahedron Lett 1969; 1975: 16
6b Kumar A, Rao GK, Saleem F, Singh AK. Dalton Trans 2012; 41: 11949
6c Ando T, Kwon TS, Kitagawa A. et al. Macromol Chem Phys 1996; 197: 2803
6d Wirth T. Tetrahedron 1999; 55: 1
6e Crich D, Zou Y. J Org Chem 2005; 70: 3309
6f van der Toorn JC, Kemperman G, Sheldon RA, Arends IWCE. J Org Chem 2009; 74: 3085
6g Sharma AK, Joshi H, Bhaskar R, Kumar S, Singh AK. Dalton Trans 2017; 46: 2485-2496

7a Kondo T, Mitsudo T-A. Chem Rev 2000; 100: 3205-3220
7b Beletskaya IP, Ananikov VP. Chem Rev 2011; 111: 1596-1636
7c Bhadra S, Saha A, Ranu BC. J Org Chem 2010; 75: 4864
7d Zheng B, Gong Y, Xu H-J. Tetrahedron 2013; 69: 5342
7e Yu J-T, Guo H, Yi Y, Fei H, Jiang Y. Adv Synth Catal 2014; 356: 749
7f Barahman M, Zhila H. Synlett 2016; 27: 777
7g Matheis C, Wagner V, Goossen LJ. Chem Eur J 2016; 22: 79
7h Barba F, Ranz F, Batanero B. Tetrahedron Lett 2009; 50 (49) 6798-6799
7i Goldani B, Ricordi VG, Seus N, Lenardão E-J, Schumacher RF, Alves D. J Org Chem 2016; 81: 11472-11476
7j Xu T, Zhou X, Xiao X. et al. J Org Chem 2022; 87: 8672-8684

8a Taniguchi N. J Org Chem 2007; 72: 1241
8b Ren K, Wang M, Wang L. Org Biomol Chem 2009; 7: 4858
8c Ricordi VG, Freitas CS, Perin G. et al. Green Chem 2012; 14: 1030
8d Nishiyama Y, Tokunaga K, Sonoda N. Org Lett 1999; 1: 1725
8e Millois C, Diaz P. Org Lett 2000; 2: 1705
8f Beletskaya IP, Sigeev AS, Peregudov AS, Petrovskii PV, Khrustalev VN. Chem Lett 2010; 39: 720
8g Zhao H, Hao W, Xi Z, Cai M. New J Chem 2011; 35: 2661

9a Rej S, Ano Y, Chatani N. Chem Rev 2020; 120: 1788
9b Goswami N, Bhattacharya T, Maiti D. Nat Rev Chem 2021; 5: 646
9c Rampon DS, Luz EQ, Lima DB, Balaguez RA, Schneider PH, Alves D. Dalton Trans 2019; 48: 9851-9905
9d Sinha SK, Guin S, Maiti S, Biswas JP, Porey S, Maiti D. Chem Rev 2022; 122: 5682
9e Sinha SK, Ghosh P, Jain S. et al. Chem Soc Rev 2023; 52: 7461
9f Ma W, Kaplaneris N, Fang X, Gu L, Mei R, Ackermann L. Org Chem Front 2020; 7: 1022-1060
9g Rampon DS, Seckler D, Luz EQ. et al. Org Biomol Chem 2022; 20: 6072-6177

10a Chen X, Hao XS, Goodhue CE, Yu JQ. J Am Chem Soc 2006; 128: 6790
10b Chu L, Yue X, Qing F. Org Lett 2010; 12 (07) 1644-1647
10c Tran LD, Popov I, Daugulis O. J Am Chem Soc 2012; 134: 18237
10d Liu S, Li X, Shi T. et al. Eur J Org Chem 2017; 2280-2289
10e Yan S-Y, Liu Y-J, Liu B, Liu Y-H, Shi B-F. Chem Commun 2015; 51: 4069-4072
10f Lin C, Li D, Wang B, Yao J, Zhang Y. Org Lett 2015; 17: 1328-1331
10g Xu C, Shen Q. Org Lett 2014; 16: 2046-2049
10h Iwasaki M, Iyanaga M, Tsuchiya Y. et al. Chem Eur J 2014; 20: 2459-2462
10i Yang Y, Hou W, Qin L. et al. Chem Eur J 2014; 20: 416-420
10j Xie W, Li B, Wang B. J Org Chem 2015; 81 (02) 396-403

11a Mandal A, Sahoo H, Baidya M. Org Lett 2016; 18: 3202
11b Pati TK, Molla SA, Ghosh NN. et al. J Org Chem 2024; 89: 6798-6812
11c Iwasaki M, Tsuchiya Y, Nakajima K, Nishihara Y. Org Lett 2014; 16 (18) 4920-4923
11d Badshah G, Gomes CMB, Ali S. et al. J Org Chem 2023; 88: 14033

12a Daugulis O, Do H-Q, Shabashov D. Acc Chem Res 2009; 42: 1074
12b Wendlandt AE, Suess AM, Stahl SS. Angew Chem Int Ed 2011; 50: 11062
12c Hirano K, Miura M. Chem Commun 2012; 48: 10704
12d Guo X-X, Gu D-W, Wu Z, Zhang W. Chem Rev 2015; 115: 1622
12e Shang M, Sun S-Z, Wang H-L, Wang M-M, Dai H-X. Synthesis 2016; 48: 4381
12f Wang Z, Kuninobu Y, Kanai M. Org Lett 2014; 16: 4790-4793
12g Manna P, Chatterjee A, Kundu M. et al. Synthesis 2025; 57: 1199-1212

13a Harrison TS, Keating GM. CNS Drugs 2005; 19: 65-89
13b Husinec S, Markovic R, Petkovic M, Nasufovic V, Savic VA. Org Lett 2011; 13: 2286-2289
13c Huang HW, Ji XC, Tang XD, Zhang M, Li XW, Jiang HF. Org Lett 2013; 15: 6254-6257
13d Gao Y, Yin MZ, Wu WQ, Huang HW, Jiang HF. Adv Synth Catal 2013; 355: 2263-2273
13e Iwama S, Tanaka T, Yajima N. WO2010/055911A1 2010
13f Parlow JJ, Stevens AM, Stegeman RA, Stallings WC, Kurumbail RG, South MS. J Med Chem 2003; 46: 4297-4312

14a Mondal B, Ghosh P, Kundu M, Das S. Org Biomol Chem 2021; 19: 1604-1609
14b Hajra A, Ghosh P, Roy C, Kundu M, Ghosh S, Das S. Org Bio Chem 2024; 22: 6617-6630
14c Joardar S, Rao GP, Jakkani S. et al. Synthesis 2025; 57: 2207-2220

15 Garamvolgyi R, Dobos J, Sipos A. et al. Eur J Med Chem 2016; 108: 623

Supplementary Material

Supplementary Material (PDF) (opens in new window)