Palladium-Catalyzed C7–H (Hetero)arylation of Pyrazolo[1,5-a]pyrazines with Heteroarenes and Aryl Iodides with the Assistance of Silver Salts

Abstract

Pyrazolo[1,5-a]pyrazines coupled with heteroarenes and aryl iodides selectively at the C7 position to afford a broad library of bi(hetero)aryl structures under ligand-free palladium-catalyzed conditions. The key to the success of the reaction is the use of silver salts as the oxidant or the base, allowing the regioselective C–H bond functionalization to occur under relatively mild conditions.

Key words

C–H bond functionalization - fused-ring systems - heteroarenes - homogeneous catalysis - synthetic methods

Publication History

Received: 13 December 2022

Accepted after revision: 30 January 2023

Article published online:
06 March 2023

• References

• 1a Gerstenberger BS, Ambler C, Arnold EP, Banker ME, Brown MF, Clark JD, Dermenci A, Dowty ME, Fensome A, Fish S, Hayward MM, Hegen M, Hollingshead BD, Knafels JD, Lin DW, Lin TH, Owen DR, Saiah E, Sharma R, Vajdos FF, Xing L, Yang X, Yang X, Wright SW. J. Med. Chem. 2020; 63: 13561
• 1b Martínez González S, Hernández AI, Álvarez RM, Rodríguez A, Ramos-Lima F, Bischoff JR, Albarrán MI, Cebriá A, Hernández-Encinas E, García-Arocha J, Cebrián D, Blanco-Aparicio C, Pastor J. Bioorg. Med. Chem. Lett. 2017; 27: 4794
• 1c Ratni H, Karp GM, Weetall M, Naryshkin NA, Paushkin SV, Chen KS, McCarthy KD, Qi H, Turpoff A, Woll MG, Zhang X, Zhang N, Yang T, Dakka A, Vazirani P, Zhao X, Pinard E, Green L, David-Pierson P, Tuerck D, Poirier A, Muster W, Kirchner S, Mueller L, Gerlach I, Metzger F. J. Med. Chem. 2016; 59: 6086
• 2a Bozhanov VI, Bohdan DP, Borysov OV, Silin AV, Zaremba OV, Avramenko MM, Volochnyuk DM, Ryabukhin SV, Gavrilenko KS. ChemistrySelect 2022; 7: e202104287
• 2b Barsanti PA, Aversa RJ, Jin X, Pan Y, Lu Y, Elling R, Jain R, Knapp M, Lan J, Lin X, Rudewicz P, Sim J, Taricani L, Thomas G, Xiao L, Yue Q. ACS Med. Chem. Lett. 2015; 6: 37
• 3a Lindsay-Scott PJ, Charlesworth NG, Grozavu A. J. Org. Chem. 2017; 82: 11295
• 3b Mousseau JJ, Bull JA, Ladd CL, Fortier A, Sustac Roman D, Charette AB. J. Org. Chem. 2011; 76: 8243

Several reviews on C–H arylation, see:
• 4a Caro-Diaz EJ. E, Urbano M, Buzard DJ, Jones RM. Bioorg. Med. Chem. Lett. 2016; 26: 5378
• 4b Yamaguchi J, Yamaguchi AD, Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
• 4c Yuan S, Chang J, Yu B. Top. Curr. Chem. 2020; 378: 23
• 4d Albano G, Punzi A, Capozzi MA. M, Farinola GM. Green Chem. 2022; 24: 1809
• 4e Hagui W, Doucet H, Soulé J.-F. Chem 2019; 5: 2006
• 4f Li B, Ali AI. M, Ge H. Chem 2020; 6: 2591 ; and references therein
• 5 Choy PY, Wong SM, Kapdi A, Kwong FY. Org. Chem. Front. 2018; 5: 288
• 6a Faarasse S, El Brahmi N, Guillaumet G, El Kazzouli S. Molecules 2021; 26: 5763
• 6b Aziz J, Piguel S. Synthesis 2017; 49: 4562
• 7a Bedford RB, Durrant SJ, Montgomery M. Angew. Chem. Int. Ed. 2015; 54: 8787
• 7b Oh KH, Kim SM, Lee MJ, Park JK. Adv. Synth. Catal. 2015; 357: 3927
• 7c Wu H.-C, Chu J.-H, Li C.-W, Hwang L.-C, Wu M.-J. Organometallics 2016; 35: 288
• 8 Nguyen TV. Q, Poli L, Garrison AT. Chem. Commun. 2022; 58: 827
• 9 Cs₂CO₃ could facilitate the H/D exchange of (hetero)arenes and DMSO-d ₆ in the absence of D₂O, see: Salamanca V, Albéniz AC. Eur. J. Org. Chem. 2020; 3206

Formation of (hetero)arene-Ag complex was generally proposed when silver salt was indispensable for C–H bond cleavage (experimentally confirmed when Ag salt was crucial for H/D exchange), for example, see:
• 10a Zhang H.-H, Wang C.-X, Sheng F.-F, Liu K.-H, Gu J.-G, Shen K, Sun Z.-Y, Hong K. Synthesis 2022; 54: 4025
• 10b Tlahuext-Aca A, Lee SY, Sakamoto S, Hartwig JF. ACS Catal. 2021; 11: 1430
• 10c Liu KH, Hu GQ, Wang CX, Sheng FF, Bai JW, Gu JG, Zhang HH. Org. Lett. 2021; 23: 5626

Silver cation could act as iodide scavenger to remove iodide from palladium, see:
• 11a Arroniz C, Denis JG, Ironmonger A, Rassias G, Larrosa I. Chem. Sci. 2014; 5: 3509
• 11b Srinivasan R, Dey A, Nagarajan NS, Kumaran RS, Gandhi T, Maiti D. Chem. Commun. 2017; 53: 11709
• 11c Joshi A, Semwal R, Suresh E, Adimurthy S. Chem. Commun. 2019; 55: 10888