Sterically Controlled C–H Borylation and Silylation of (Hetero)arenes Using Pyrazolonaphthyridine Ligands

Abstract

We have developed iridium-catalyzed C–H borylation and silylation reactions using pyrazolonaphthyridine (PzNPy) ligands. The readily tunable PzNPy system provides easy control of the ligand characteristics, enabling selective functionalization at the least hindered positions. With the new catalytic system, 1,4-disubstituted and multi-substituted toluene derivatives preferentially underwent borylation at benzylic positions, whereas 1,3-disubstituted arenes favored the least hindered sp2 positions. The Ir/PzNPy system also showed applicability in the C–H borylation of heteroarenes and metallocenes. Furthermore, increasing steric bulk near nitrogen atoms of ligand enabled C–H silylation of five-membered heteroarenes. These results expand the toolbox of bidentate nitrogen ligands for the development of iridium-catalyzed C–H functionalization reactions, suggesting the potential of tailorable PzNPy ligands to extend beyond their applications in palladium catalysis.

Keywords

Borylation - Silylation - Ligand - Iridium - C–H Activation

Publication History

Received: 19 May 2025

Accepted after revision: 23 June 2025

Article published online:
31 July 2025

• References

• 1 Kaes C, Katz A, Hosseini MW. Chem Rev 2000; 100: 3553-3590
• 2a Ishiyama T, Takagi J, Ishida K, Miyaura N, Anastasi NR, Hartwig JF. J Am Chem Soc 2002; 124: 390-391
• 2b Ishiyama T, Takagi J, Hartwig JF, Miyaura N. Angew Chem, Int Ed 2002; 41: 3056-3058
• 3a Mkhalid IAI, Barnard JH, Marder TB, Murphy JM, Hartwig JF. Chem Rev 2010; 110: 890-931
• 3b Wright JS, Scott PJH, Steel PG. Angew Chem, Int Ed 2021; 60: 2796-2821
• 3c Bisht R, Haldar C, Hassan MMM, Hoque ME, Chaturvedi J, Chattopadhyay B. Chem Soc Rev 2022; 51: 5042-5100
• 3d Hu J, Lv J, Shi Z. Trends Chem 2022; 4: 685-698
• 4a Hoque ME, Hassan MMM, Haldar C. et al. Synthesis 2022; 54: 3328-3340
• 4b Miller SL, Chotana GA, Fritz JA, Chattopadhyay B, Maleczka RE, Smith MR. Org Lett 2019; 21: 6388-6392
• 4c Hoque ME, Hassan MMM, Chattopadhyay B. J Am Chem Soc 2021; 143: 5022-5037
• 5a Nippa DF, Atz K, Hohler R. et al. Nat Chem 2024; 16: 239-248
• 5b Caldeweyher E, Elkin M, Gheibi G. et al. J Am Chem Soc 2023; 145: 17367-17376
• 6 Tatsuo I, Kousaku I, Jun T, Norio M. Chem Lett 2001; 30: 1082-1083
• 7a Shimada S, Batsanov AS, Howard JAK, Marder TB. Angew Chem, Int Ed 2001; 40: 2168-2171
• 7b Mertins K, Zapf A, Beller M. J Mol Catal A: Chem 2004; 207: 21-25
• 8a Palmer WN, Obligacion JV, Pappas I, Chirik PJ. J Am Chem Soc 2016; 138: 766-769
• 8b Jayasundara CRK, Sabasovs D, Staples RJ, Oppenheimer J, Smith III MR, Maleczka Jr RE. Organometallics 2018; 37: 1567-1574
• 8c Ghosh P, Schoch R, Bauer M, Jacobi von Wangelin A. Angew Chem, Int Ed 2022; 61: e202110821
• 9 Palmer WN, Zarate C, Chirik PJ. J Am Chem Soc 2017; 139: 2589-2592
• 10 Jones MR, Fast CD, Schley ND. J Am Chem Soc 2020; 142: 6488-6492
• 11 Larsen MA, Wilson CV, Hartwig JF. J Am Chem Soc 2015; 137: 8633-8643
• 12a Yu IF, Wilson JW, Hartwig JF. Chem Rev 2023; 123: 11619-11663
• 12b Khatua H, Das S, Patra S, Chattopadhyay B. Synthesis 2023; 55: 3434-3453
• 13a Kim HT, Kang E, Kim M, Joo JM. Org Lett 2021; 23: 3657-3662
• 13b Kang E, Jeon JE, Jeong S, Kim HT, Joo JM. Chem Commun 2021; 57: 11791-11794
• 13c Müller S, Lee W, Song JY, Kang E, Joo JM. Chem Commun 2022; 58: 10809-10812
• 13d Kim J, Joo JM. Bull Korean Chem Soc 2022; 43: 1173-1176
• 13e Yun SJ, Kim J, Kang E. et al. ACS Catal 2023; 13: 4042-4052
• 14a Jeong S, Joo JM. Acc Chem Res 2021; 54: 4518-4529
• 14b Kang E, Joo JM. Synthesis 2023; 56: 1549-1562
• 15 Cao Z-C, Luo F-X, Shi W-J, Shi Z-J. Org Chem Front 2015; 2: 1505-1510
• 16 Datta A, Köllhofer A, Plenio H. Chem Commun 2004; 1508-1509
• 17a Karmel C, Chen Z, Hartwig JF. J Am Chem Soc 2019; 141: 7063-7072
• 17b Karmel C, Rubel CZ, Kharitonova EV, Hartwig JF. Angew Chem Int Ed 2020; 59: 6074-6081
• 18 Nasso I, Bedel S, Galaup C, Picard C, Jal P. Eur J Inorg Chem 2008; 2064-2074
• 19 Pawar GG, Wu HB, De S, Ma DW. Adv Synth Catal 2017; 359: 1631-1636
• 20 Shavaleev NM, Kessler F, Grätzel M, Nazeeruddin MK. Inorg Chim Acta 2013; 407: 261-268
• 21 Mao LJ, Szabó KJ, Marder TB. Org Lett 2017; 19: 1204-1207
• 22 Newar R, Begum W, Akhtar N. et al. Eur J Inorg Chem 2022; 2022
• 23a Murata M, Oda T, Sogabe Y, Tone H, Namikoshi T, Watanabe S. Chem Lett 2011; 40: 962-963
• 23b Wang G, Liu L, Wang H. et al. J Am Chem Soc 2017; 139: 91-94
• 24 Colvin AE, Mortellaro MA, Modzelewska A. Preparation of arylboronic acid derivatives as oxidation resistant indicator molecules. WO2008066921, 2008
• 25 Kim S, Treacy JW, Nelson YA. et al. Nat Commun 2023; 14: 1671
• 26 Lima F, Kabeshov MA, Tran DN. et al. Angew Chem, Int Ed 2016; 55: 14085-14089
• 27 Boebel TA, Hartwig JF. Organometallics 2008; 27: 6013-6019
• 28 Klein LL, Petukhova V. Synth Commun 2013; 43: 2242-2245
• 29 Tse MK, Cho JY, Smith MR. Org Lett 2001; 3: 2831-2833
• 30 Bastick KAC, Watson AJB. ACS Catal 2023; 13: 7013-7018
• 31 Bose SK, Deißenberger A, Eichhorn A, Steel PG, Lin Z, Marder TB. Angew Chem, Int Ed 2015; 54: 11843-11847
• 32 Wang G, Xu L, Li P. J Am Chem Soc 2015; 137: 8058-8061
• 33 Guerrand HDS, Vaultier M, Pinet S, Pucheault M. Adv Synth Catal 2015; 357: 1167-1174
• 34 Marciasini LD, Richy N, Vaultier M, Pucheault M. Adv Synth Catal 2013; 355: 1083-1088
• 35 Li ZQ, Liang ZB, Wang YQ, Yu P. Res Chem Intermed 2013; 39: 1917-1926
• 36 Tanaka S, Saito Y, Yamamoto T, Hattori T. Org Lett 2018; 20: 1828-1831
• 37 Chotana GA, Kallepalli VA, Maleczka RE, Smith MR. Tetrahedron 2008; 64: 6103-6114
• 38 Harrisson P, Morris J, Marder TB, Steel PG. Org Lett 2009; 11: 3586-3589
• 39 Datta A, Köllhofer A, Plenio H. Chem Commun 2004; 1508-1509
• 40 Braunschweig H, Grünewald B, Schwab K, Sigritz R. Eur J Inorg Chem 2009; 4860-4863
• 41 Sato M, Maruyama G, Tanemura A. J Organomet Chem 2002; 655: 23-30
• 42 Fang H, Guo L, Zhang Y, Yao W, Huang Z. Org Lett 2016; 18: 5624-5627