Benzoxazole or Benzothiazole as an Innate Directing Group for Palladium- and Ruthenium-Catalyzed Complementary C–H Arylation: Functionalization of Biorelevant Heterocyclic Scaffolds

Abstract

The benzoxazole and benzothiazole moieties were used as innate directing groups for Pd(II)- and Ru(II)-catalyzed C–H arylation of the biorelevant heterocycles 2-arylbenzoxazole and 2-arylbenzothiazole with diverse iodoarenes; palladium and ruthenium catalysis could be used complementarily. The use of σ-donor ligands, such as N,N-dimethylacetamide in the Pd(II) catalytic cycle, and σ-donor/π-acceptor ligands, such as PPh₃ in the Ru(II) catalytic cycle, enhanced the arylation rate significantly and was governed by the C–H acidity of the C2-aryl ring of the 2-arylbenzoxazole or 2-arylbenzothiazole. These approaches have a broad substrate scope with respect to coupling partners, to accommodate electron-neutral, electron-rich, as well as electron-deficient iodoarenes; the C2-aryl unit of the 2-arylbenzoxazole or 2-arylbenzothiazole exhibited a high degree of site selectivity at the ortho C–H position, affording only monoarylated derivatives in decent yields; the reactions are functional-group-tolerant and applicable to gram-scale production.

Key words

innate/native directing group - palladium catalysis - ruthenium catalysis - complementary C–H activation - monoarylation - biosignificant scaffolds - site selectivity

Publication History

Received: 06 September 2023

Accepted after revision: 17 October 2023

Accepted Manuscript online:
17 October 2023

Article published online:
13 November 2023

• References


For selected representative reviews, see:
• 1a Grover J, Prakash G, Goswami N, Maiti D. Nat. Commun. 2022; 13: 1085
• 1b Gandeepan P, Müller T, Zell D, Cera G, Warratz S, Ackermann L. Chem. Rev. 2019; 119: 2192
• 1c Gensch T, Hopkinson M, Glorius F, Wencel-Delord J. Chem. Soc. Rev. 2016; 45: 2900
• 1d Wencel-Delord J, Dröge T, Liu F, Glorius F. Chem. Soc. Rev. 2011; 40: 4740
• 1e Chiusoli GP, Catellani M, Costa M, Motti E, Ca’ ND, Maestri G. Coord. Chem. Rev. 2010; 254: 456
• 1f Ackermann L, Vicente R, Kapdi AR. Angew. Chem. Int. Ed. 2009; 48: 9792
• 2 Dalton T, Faber T, Glorius F. ACS Cent. Sci. 2021; 7: 245
• 3a Davies HM. L, Morton D. J. Org. Chem. 2016; 81: 343
• 3b Kallepalli VA, Gore KA, Shi F, Sanchez L, Chotana GA, Miller SL, Maleczka RE. Jr, Smith MR. III. J. Org. Chem. 2015; 80: 8341

For selected representative examples, see:
• 4a Zhang L, Ritter T. J. Am. Chem. Soc. 2022; 144: 2399
• 4b Friis SD, Johansson MJ, Ackermann L. Nat. Chem. 2020; 12: 511
• 4c Porey S, Zhang X, Bhowmick S, Singh VK, Guin S, Paton RS, Maiti D. J. Am. Chem. Soc. 2020; 142: 3762
• 4d Simonetti M, Cannas DM, Just-Baringo X, Vitorica-Yrezabal IJ, Larrosa I. Nat. Chem. 2018; 10: 724
• 4e Cernak T, Dykstra KD, Tyagarajan S, Vachal P, Krska SW. Chem. Soc. Rev. 2016; 45: 546
• 4f Campbell MG, Ritter T. Org. Process Res. Dev. 2014; 18: 474
• 4g Schönherr H, Cernak T. Angew. Chem. Int. Ed. 2013; 52: 12256
• 4h Dai H.-X, Stepan AF, Plummer MS, Zhang Y.-H, Yu J.-Q. J. Am. Chem. Soc. 2011; 133: 7222

For selected representative examples, see:
• 5a Baudoin O. Angew. Chem. Int. Ed. 2020; 59: 17798
• 5b Abrams DJ, Provencher PA, Sorensen EJ. Chem. Soc. Rev. 2018; 47: 8925
• 5c Yamaguchi J, Yamaguchi AD, Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
• 5d McMurray L, O’Hara F, Gaunt MJ. Chem. Soc. Rev. 2011; 40: 1885
• 5e Giri R, Shi B.-F, Engle KM, Maugel N, Yu J.-Q. Chem. Soc. Rev. 2009; 38: 3242
• 6 Lam NY. S, Wu K, Yu J.-Q. Angew. Chem. Int. Ed. 2021; 60: 15767
• 7a Hartwig JF, Larsen MA. ACS Cent. Sci. 2016; 2: 281
• 7b Newhouse T, Baran PS. Angew. Chem. Int. Ed. 2011; 50: 3362

For selected representative examples, see:
• 8a Iqbal Z, Joshi A, De S R. Adv. Synth. Catal. 2020; 362: 5301
• 8b Sambiagio C, Schönbauer D, Blieck R, Dao-Huy T, Pototschnig G, Schaaf P, Wiesinger T, Zia MF, Wencel-Delord J, Besset T, Maes BU. W, Schnürch M. Chem. Soc. Rev. 2018; 47: 6603
• 8c Chen Z, Wang B, Zhang J, Yu W, Liu Z, Zhang Y. Org. Chem. Front. 2015; 2: 1107
• 8d Zhang M, Zhang Y, Jie X, Zhao H, Li G, Su W. Org. Chem. Front. 2014; 1: 843
• 8e Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
• 9a Albrecht M. Chem. Rev. 2010; 110: 576
• 9b Cope AC, Siekman RW. J. Am. Chem. Soc. 1965; 87: 3272
• 9c Kleiman JP, Dubeck M. J. Am. Chem. Soc. 1963; 85: 1544
• 10 Neufeldt SR, Sanford MS. Acc. Chem. Res. 2012; 45: 936
• 11 Seth K. In Handbook of CH-Functionalization, 1st ed. Maiti D. Wiley-VCH; Weinheim: 2023. Chap. 158

For selected representative examples, see:
• 12a Brückl T, Baxter RD, Ishihara Y, Baran PS. Acc. Chem. Res. 2012; 45: 826
• 12b Engle KM, Mei T.-S, Wasa M, Yu J.-Q. Acc. Chem. Res. 2012; 45: 788
• 12c Arockiam PB, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879

For selected representative examples, see:
• 13a Rej S, Ano Y, Chatani N. Chem. Rev. 2020; 120: 1788
• 13b Gramage-Doria R. Chem. Eur. J. 2020; 26: 9688
• 13c Daugulis O, Roane J, Tran LD. Acc. Chem. Res. 2015; 48: 1053
• 13d Sarkar SD, Liu W, Kozhushkov SI, Ackermann L. Adv. Synth. Catal. 2014; 356: 1461
• 13e Rouquet G, Chatani N. Angew. Chem. Int. Ed. 2013; 52: 11726
• 13f Daugulis O, Do H.-Q, Shabashov D. Acc. Chem. Res. 2009; 42: 1074

For selected representative examples, see:
• 14a Zarkadoulas A, Zgouleta I, Tzouras NV, Vougioukalakis GC. Catalysts 2021; 11: 554
• 14b Cizikovs A, Lukasevics L, Grigorjeva L. Tetrahedron 2021; 93: 132307
• 14c Rani G, Luxami V, Paul K. Chem. Commun. 2020; 56: 12479
• 14d Font M, Quibell JM, Perry GJ. P, Larrosa I. Chem. Commun. 2017; 53: 5584
• 14e Zhang J, Shrestha R, Hartwig JF, Zhao P. Nat. Chem. 2016; 8: 1144
• 14f Huang L, Biafora A, Zhang G, Bragoni V, Gooßen LJ. Angew. Chem. Int. Ed. 2016; 55: 6933
• 14g Cornella J, Righi M, Larrosa I. Angew. Chem. Int. Ed. 2011; 50: 9429
• 14h Maehara A, Tsurugi H, Satoh T, Miura M. Org. Lett. 2008; 10: 1159

For selected representative examples, see:
• 15a Trouvé J, Rajeshwaran P, Tomasini M, Perennes A, Roisnel T, Poater A, Gramage-Doria R. ACS Catal. 2023; 13: 7715
• 15b Gillespie JE, Fanourakis A, Phipps RJ. J. Am. Chem. Soc. 2022; 144: 18195
• 15c Dutta U, Maiti S, Bhattacharya T, Maiti D. Science 2021; 372: eabd5992
• 15d Trouvé J, Zardi P, Al-Shehimy S, Roisnel T, Gramage-Doria R. Angew. Chem. Int. Ed. 2021; 60: 18006
• 15e Mihai MT, Genov GR, Phipps RJ. Chem. Soc. Rev. 2018; 47: 149
• 15f Rasheed OK, Sun B. ChemistrySelect 2018; 3: 5689
• 15g Haldar C, Hoque ME, Bisht R, Chattopadhyay B. Tetrahedron Lett. 2018; 59: 1269
• 15h Hoque ME, Bisht R, Haldar C, Chattopadhyay B. J. Am. Chem. Soc. 2017; 139: 7745
• 15i Beer PD, Gale PA, Smith DK. Supramolecular Chemistry . Oxford University Press; New York: 1999

For selected representative examples, see:
• 16a Zu B, Guo Y, Ke J, He C. Synthesis 2021; 53: 2029
• 16b Gandeepan P, Ackermann L. Chem 2018; 4: 199
• 16c Bhattacharya T, Pimparkar S, Maiti D. RSC Adv. 2018; 8: 19456
• 16d Li B, Seth K, Niu B, Pan L, Yang H, Ge H. Angew. Chem. Int. Ed. 2018; 57: 3401
• 16e Liu X.-H, Park H, Hu J.-H, Hu Y, Zhang Q.-L, Wang B.-L, Sun B, Yeung K.-S, Zhang F.-L, Yu J.-Q. J. Am. Chem. Soc. 2017; 139: 888
• 16f Dydio P, Reek JN. H. Chem. Sci. 2014; 5: 2135
• 16g Rousseau G, Breit B. Angew. Chem. Int. Ed. 2011; 50: 2450
• 17 Lu Q, Greßies S, Cembellín S, Klauck FJ. R, Daniliuc CG, Glorius F. Angew. Chem. Int. Ed. 2017; 56: 12778
• 18 Liu L, Durai M, Doucet H. Eur. J. Org. Chem. 2022; e202200007
• 19 Tomberg A, Muratore M. É, Johansson MJ, Terstiege I, Sköld C, Norrby P.-O. iScience 2019; 20: 373
• 20a Lamb YN, Deeks ED. Drugs 2019; 79: 863
• 20b Scott LJ. Drugs 2014; 74: 1371
• 20c Said G, Grippon S, Kirkpatrick P. Nat. Rev. Drug Discovery 2012; 11: 185
• 20d Hohmann C, Schneider K, Bruntner C, Irran E, Nicholson G, Bull AT, Jones AL, Brown R, Stach JE. M, Goodfellow M, Beil W, Krämer M, Imhoff JF, Süssmuth RD, Fiedler H.-P. J. Antibiot. 2009; 62: 99
• 20e Mortimer CG, Wells G, Crochard J.-P, Stone EL, Bradshaw TD, Stevens MF. G, Westwell AD. J. Med. Chem. 2006; 49: 179
• 20f Mathis CA, Wang Y, Holt DP, Huang G.-F, Debnath ML, Klunk WE. J. Med. Chem. 2003; 46: 2740
• 20g Anderson R, Lukey PT, Naudé SP. E, Jooné G. Agents Actions 1984; 14: 238
• 20h Dunwell DW, Evans D. J. Med. Chem. 1977; 20: 797
• 20i Dunwell DW, Evans D, Hicks TA. J. Med. Chem. 1975; 18: 1158
• 21 Seth K, Garg SK, Kumar R, Purohit P, Meena VS, Goyal R, Banerjee UC, Chakraborti AK. ACS Med. Chem. Lett. 2014; 5: 512
• 22 Ashraf M, Shaik TB, Malik MS, Syed R, Mallipeddi PL, Vardhan MV. P. S. V, Kamal A. Bioorg. Med. Chem. Lett. 2016; 26: 4527
• 23 Racané L, Ptiček L, Fajdetić G, Tralić-Kulenović V, Klobučar M, Pavelić SK, Perić M, Paljetak H. Č, Verbanac D, Starčević K. Bioorg. Chem. 2020; 95: 103537
• 24a Pipaliya BV, Seth K, Chakraborti AK. Chem. Asian J. 2021; 16: 87
• 24b Pipaliya BV, Chakraborti AK. J. Org. Chem. 2017; 82: 3767
• 24c Pipaliya BV, Chakraborti AK. ChemCatChem 2017; 9: 4191
• 24d Seth K, Nautiyal M, Purohit P, Parikh N, Chakraborti AK. Chem. Commun. 2015; 51: 191
• 25a Hoffmann T, Gastreich M. Drug Discovery Today 2019; 24: 1148
• 25b Reymond J.-L, Awale M. ACS Chem. Neurosci. 2012; 3: 649
• 25c Reymond J.-L, van Deursen R, Blum LC, Ruddigkeit L. Med. Chem. Commun. 2010; 1: 30
• 26 Seth K, Purohit P, Chakraborti AK. Org. Lett. 2014; 16: 2334
• 27 Brown DG, Boström J. J. Med. Chem. 2016; 59: 4443
• 28 Yang F, Wu Y, Zhu Z, Zhang J, Li Y. Tetrahedron 2008; 64: 6782
• 29 Yang F, Wu Y, Li Y, Wang B, Zhang J. Tetrahedron 2009; 65: 914
• 30 Ding Q, Ji H, Wang D, Lin Y, Yu W, Peng Y. J. Organomet. Chem. 2012; 711: 62
• 31 Peng H, Liu Q, Sun Y, Luo B, Yu T, Huang P, Zhu D, Wen S. Org. Chem. Front. 2022; 9: 1137
• 32 Only one example is mentioned for direct ortho C–H phenylation of isolated 2-phenylbenzoxazole with external iodobenzene under Pd(II) catalysis.
• 33 Purohit P, Seth K, Kumar A, Chakraborti AK. ACS Catal. 2017; 7: 2452
• 34 Leckie SM, Harkness GJ, Clarke ML. Chem. Commun. 2014; 50: 11511
• 35 Belluco U, Giustiniani M, Graziani M. J. Am. Chem. Soc. 1967; 89: 6494
• 36 Labinger JA, Bercaw JE. Nature 2002; 417: 507
• 37 Ryabov AD. Chem. Rev. 1990; 90: 403

For the HOMO–LUMO interaction of a catalytic metal center and a C–H bond, see:
• 38a Seth K. Org. Chem. Front. 2022; 9: 3102
• 38b Hashiguchi BG, Bischof SM, Konnick MM, Periana RA. Acc. Chem. Res. 2012; 45: 885
• 39a Boström J, Brown DG, Young RJ, Keserü GM. Nat. Rev. Drug Discovery 2018; 17: 709
• 39b Roughley SD, Jordan AM. J. Med. Chem. 2011; 54: 3451

For selected representative examples, see:
• 40a Findlay MT, Hogg AS, Douglas JJ, Larrosa I. Green Chem. 2023; 25: 2394
• 40b Kobayashi Y, Kashiwa M, Sonoda M, Kirihata M, Tanimori S. Synthesis 2014; 46: 3185
• 40c Li B, Dixneuf PH. Chem. Soc. Rev. 2013; 42: 5744
• 40d Kozhushkov SI, Potukuchi HK, Ackermann L. Catal. Sci. Technol. 2013; 3: 562
• 40e Aihara Y, Chatani N. Chem. Sci. 2013; 4: 664
• 40f Luo N, Yu Z. Chem. Eur. J. 2010; 16: 787
• 40g Ackermann L. Angew. Chem. Int. Ed. 2006; 45: 2619
• 41 Liu M, Zhou L, Luo X, Wan C, Xu L. Catalysts 2020; 10: 788
• 42 Satoh T, Kawamura Y, Miura M, Nomura M. Angew. Chem. Int. Ed. 1997; 36: 1740
• 43 Barrios-Landeros F, Carrow BP, Hartwig JF. J. Am. Chem. Soc. 2008; 130: 5842
• 44a Flegeau EF, Bruneau C, Dixneuf PH, Jutand A. J. Am. Chem. Soc. 2011; 133: 10161
• 44b Ackermann L, Vicente R, Potukuchi HK, Pirovano V. Org. Lett. 2010; 12: 5032
• 45 Benzai A, Derridj F, Doucet H, Soulé J.-F. ChemCatChem 2021; 13: 338
• 46 Mousseau JJ, Charette AB. Acc. Chem. Res. 2013; 46: 412
• 47 Hartings MR. Nat. Chem. 2012; 4: 764
• 48a Topczewski JJ, Sanford MS. Chem. Sci. 2015; 6: 70
• 48b Sehnal P, Taylor RJ. K, Fairlamb IJ. S. Chem. Rev. 2010; 110: 824
• 48c Chen X, Engle KM, Wang D.-H, Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094
• 49 Engle KM, Yu J.-Q. J. Org. Chem. 2013; 78: 8927
• 50 Wayland BB, Fitzgerald RJ, Drago RS. J. Am. Chem. Soc. 1966; 88: 4600
• 51 Miyasaka M, Fukushima A, Satoh T, Hirano K, Miura M. Chem. Eur. J. 2009; 15: 3674
• 52 Tóth BL, Monory A, Egyed O, Domján A, Bényei A, Szathury B, Novák Z, Stirling A. Chem. Sci. 2021; 12: 5152
• 53a Eissa IH, El-Haggar R, Dahab MA, Ahmed MF, Mahdy HA, Alsantali RI, Elwan A, Masurier N, Fatahala SS. J. Enzyme Inhib. Med. Chem. 2022; 37: 1587
• 53b Osmaniye D, Çelikateş BK, Sağlık BN, Levent S, Çevik UA, Çavuşoğlu BK, Ilgın S, Özkay Y, Kaplancıklı ZA. Eur. J. Med. Chem. 2021; 210: 112979
• 54a Tokala R, Mahajan S, Kiranmai G, Sigalapalli DK, Sana S, John SE, Nagesh N, Shankaraiah N. Bioorg. Chem. 2021; 106: 104481
• 54b Fu D.-J, Liu S.-M, Li F.-H, Yang J.-J, Li J. J. Enzyme Inhib. Med. Chem. 2020; 35: 1050
• 54c Elsayed MS. A, Chang S, Cushman M. Org. Biomol. Chem. 2018; 16: 108
• 54d Dhameliya TM, Tiwari R, Banerjee A, Pancholia S, Sriram D, Panda D, Chakraborti AK. Eur. J. Med. Chem. 2018; 155: 364
• 54e Seth K, Purohit P, Chakraborti AK. Curr. Med. Chem. 2017; 24: 4638
• 54f Hutchinson I, Chua M.-S, Browne HL, Trapani V, Bradshaw TD, Westwell AD, Stevens MF. G. J. Med. Chem. 2001; 44: 1446
• 54g Kashiyama E, Hutchinson I, Chua M.-S, Stinson SF, Phillips LR, Kaur G, Sausville EA, Bradshaw TD, Westwell AD, Stevens MF. G. J. Med. Chem. 1999; 42: 4172
• 55 Huheey JE, Keiter EA, Keiter RL. Inorganic Chemistry: Principles of Structure and Reactivity, 4th ed. 2004
• 56a Gorelsky SI, Lapointe D, Fagnou K. J. Org. Chem. 2012; 77: 658
• 56b Lafrance M, Rowley CN, Woo TK, Fagnou K. J. Am. Chem. Soc. 2006; 128: 8754
• 57 Gorelsky SI, Lapointe D, Fagnou K. J. Am. Chem. Soc. 2008; 130: 10848
• 58 Tan Y, Hartwig JF. J. Am. Chem. Soc. 2011; 133: 3308
• 59 García-Cuadrado D, Braga AA. C, Maseras F, Echavarren AM. J. Am. Chem. Soc. 2006; 128: 1066
• 60 For an EMD pathway of a heteroarene, see: Joo JM, Touré BB, Sames D. J. Org. Chem. 2010; 75: 4911
• 61 For an eCMD pathway of an electron-rich heteroarene, see: Wang L, Carrow BP. ACS Catal. 2019; 9: 6821
• 62 Boutadla Y, Davies DL, Macgregor SA, Poblador-Bahamonde AI. Dalton Trans. 2009; 5820
• 63 Davies DL, Macgregor SA, McMullin CL. Chem. Rev. 2017; 117: 8649
• 64 Boutadla Y, Davies DL, Macgregor SA, Poblador-Bahamonde AI. Dalton Trans. 2009; 5887
• 65a Li K, Jiang H, Zeng M, Tan C, Chen Z, Yin G. J. Org. Chem. 2022; 87: 16592
• 65b Brookhart M, Green ML. H, Parkin G. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 6908
• 66a Sunny S, Maingle M, Sheeba L, Pathan FR, Sankar JG, Juloori H, Gadewar SG, Seth K. Synthesis 2023; in press DOI: 10.1055/a-2060-3488.
• 66b Wang L, Yi W.-b, Cai C. Chem. Commun. 2011; 47: 806
• 67 Wang X, Gribkov DV, Sames D. J. Org. Chem. 2007; 72: 1476
• 68 Alharis RA, McMullin CL, Davies DL, Singh K, Macgregor SA. Faraday Discuss. 2019; 220: 386
• 69a Albano VG, Serio MD, Monari M, Orabona I, Panunzi A, Ruffo F. Inorg. Chem. 2002; 41: 2672
• 69b Liston DJ, Lee YJ, Scheidt WR, Reed CA. J. Am. Chem. Soc. 1989; 111: 6643
• 70 Ballivet-Tkatchenko D, Bremard C. J. Chem. Soc., Dalton Trans. 1983; 1143
• 71a Amatore C, Jutand A, Lemaítre F, Ricard JL, Kozuch S, Shaik S. J. Organomet. Chem. 2004; 689: 3728
• 71b Schmülling M, Grove DM, van Koten G, van Eldik R, Veldman N, Spek AL. Organometallics 1996; 15: 1384
• 72a Moermond CT. A, Puhlmann N, Brown AR, Owen SF, Ryan J, Snape J, Venhuis BJ, Kümmerer K. Environ. Sci. Technol. Lett. 2022; 9: 699
• 72b Bryan MC, Dillon B, Hamann LG, Hughes GJ, Kopach ME, Peterson EA, Pourashraf M, Raheem I, Richardson P, Richter D, Sneddon HF. J. Med. Chem. 2013; 56: 6007
• 73 Cooper TW. J, Campbell IB, Macdonald SJ. F. Angew. Chem. Int. Ed. 2010; 49: 8082