An Update on Direct C–H Bond Functionalization of Nitrogen-Containing Fused Heterocycles

Abstract

This report highlights the recent advances in direct C–H bond functionalization of 5,5- and 6,5-fused heterocycles containing at least two nitrogen atoms. Besides C–C bond formation, C–N, C–S, C–P, and C–Si bonds can also be created via a metal-catalyzed process. Some examples, where a C–H functionalization approach was applied for the synthesis of drug candidates, will be presented as well.

1 Introduction

2 C–H Functionalization Reactions of N-Containing Heterocycles

2.1 Imidazo[1,2-a]pyridines

2.2 Pyrrolo[1,2-a]pyrazines

2.3 Imidazo[1,2-b]pyrazoles

2.4 Imidazo[1,2-a]pyrimidines

2.5 Imidazo[1,2-a]pyrazines and Imidazo[1,5-a]pyrazines

2.6 Imidazo[1,2-b]pyridazines

2.7 Imidazo[4,5-b]pyridines and Imidazo[4,5-c]pyridines

2.8 Pyrazolo[3,4-b]pyridines

2.9 Pyrazolo[1,5-a]pyrimidines

2.10 Pyrrolo[2,3-d]pyrimidines and Pyrrolo[3,2-d]pyrimidines

2.11 Imidazo[1,2-b][1,2,4]triazines

2.12 Imidazo[1,2-b][1,2,4,5]tetrazines

3 Outlook

4 Conclusion

Key words

heterocycles - nitrogen - C–H bond - direct functionalization - catalysis - regioselectivity

• References

• 1a Davies HM. L. Morton D. J. Org. Chem. 2016; 81: 343
• 1b Gensch T. Hopkinson MN. Glorius F. Wencel-Delord J. Chem. Soc. Rev. 2016; 45: 2900
• 1c Labinger JA. Bercaw JE. Nature (London) 2002; 417: 507
• 2 Eicher T. Hauptmann S. The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications. 2nd ed. Wiley-VCH; Weinheim: 2003
• 3 Vitaku E. Smith DT. Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 4a Abdoli M. Mirjafary Z. Saeidian H. Kakanejadifard A. RSC Adv. 2015; 5: 44371
• 4b El Kazzouli S. Koubachi J. El Brahmi N. Guillaumet G. RSC Adv. 2015; 5: 15292
• 4c Gayakhe V. Sanghvi YS. Fairlamb IJ. S. Kapdi AR. Chem. Commun. 2015; 51: 11944
• 4d Koubachi J. El Kazzouli S. Bousmina M. Guillaumet G. Eur. J. Org. Chem. 2014; 5119
• 4e Rossi R. Bellina F. Lessi M. Manzini C. Perego LA. Synthesis 2014; 46: 2833
• 4f Sharma A. Vacchani D. Van der Eycken E. Chem. Eur. J. 2013; 19: 1158
• 5 Liang Y. Wnuk S. Molecules 2015; 20: 4874
• 6a Couty F. Evano G. In Comprehensive Heterocyclic Chemistry III . Ramsden CA. Scriven EF. V. Taylor RJ. K. Elsevier; Oxford: 2008: 409
• 6b Enguehard-Gueiffier C. Gueiffier A. Mini Rev. Med. Chem. 2007; 7: 888
• 6c Goel R. Luxami V. Paul K. Curr. Top. Med. Chem. 2016; 16: 3590
• 7a Bagdi AK. Santra S. Monir K. Hajra A. Chem. Commun. 2015; 51: 1555
• 7b Pericherla K. Kaswan P. Pandey K. Kumar A. Synthesis 2015; 47: 887
• 8 Koubachi J. El Kazzouli S. Berteina-Raboin S. Mouaddib A. Guillaumet G. Synthesis 2008; 2537
• 9 Koubachi J. Berteina-Raboin S. Mouaddib A. Guillaumet G. Synthesis 2009; 271
• 10 Zhan H. Zhao L. Li N. Chen L. Liu J. Liao J. Cao H. RSC Adv. 2014; 4: 32013
• 11 Cao H. Lei S. Liao J. Huang J. Qiu H. Chen Q. Qiu S. Chen Y. RSC Adv. 2014; 4: 50137
• 12 Ghosh M. Naskar A. Mitra S. Hajra A. Eur. J. Org. Chem. 2015; 715
• 13 Pericherla K. Khedar P. Khungar B. Kumar A. Chem. Commun. 2013; 49: 2924
• 14 Fukuyama T. Chatani N. Tatsumi J. Kakiuchi F. Murai S. J. Am. Chem. Soc. 1998; 120: 11522
• 15 Cao H. Lei S. Li N. Chen L. Liu J. Cai H. Qiu S. Tan J. Chem. Commun. 2015; 51: 1823
• 16 Lei S. Chen G. Mai Y. Chen L. Cai H. Tan J. Cao H. Adv. Synth. Catal. 2016; 358: 67
• 17 Samanta S. Mondal S. Santra S. Kibriya G. Hajra A. J. Org. Chem. 2016; 81: 10088
• 18 Monir K. Bagdi AK. Ghosh M. Hajra A. J. Org. Chem. 2015; 80: 1332
• 19 Ji X.-M. Wei L. Chen F. Tang R.-Y. RSC Adv. 2015; 5: 29766
• 20 Wu Y. Zhang H.-R. Jin R.-X. Lan Q. Wang X.-S. Adv. Synth. Catal. 2016; 358: 3528
• 21 Yadav M. Dara S. Saikam V. Kumar M. Aithagani SK. Paul S. Vishwakarma RA. Singh PP. Eur. J. Org. Chem. 2015; 6526
• 22 Mondal S. Samanta S. Jana S. Hajra A. J. Org. Chem. 2017; 82: 4504
• 23 Cao H. Chen L. Liu J. Cai H. Deng H. Chen G. Yan C. Chen Y. RSC Adv. 2015; 5: 22356
• 24 Li J. Li C. Yang S. An Y. Wu W. Jiang H. J. Org. Chem. 2016; 81: 7771
• 25 Ravi C. Reddy NN. K. Pappula V. Samanta S. Adimurthy S. J. Org. Chem. 2016; 81: 9964
• 26 Zhu W. Ding Y. Bian Z. Xie P. Xu B. Tang Q. Wu W. Zhou A. Adv. Synth. Catal. 2017; 359: 2215
• 27 Ding Y. Xie P. Zhu W. Xu B. Zhao W. Zhou A. RSC Adv. 2016; 6: 81932
• 28 Ravi C. Chandra Mohan D. Adimurthy S. Org. Biomol. Chem. 2016; 14: 2282
• 29a Lecoutey C. Rochais C. Genest D. Butt-Gueulle S. Ballandonne C. Corvaisier S. Dulin F. Lepailleur A. Sopkova-de Oliveira Santos J. Dallemagne P. Med. Chem. Commun. 2012; 3: 627
• 29b Micheli F. Bertani B. Bozzoli A. Crippa L. Cavanni P. Di Fabio R. Donati D. Marzorati P. Merlo G. Paio A. Perugini L. Zarantonello P. Bioorg. Med. Chem. Lett. 2008; 18: 1804
• 30 Park S. Jung Y. Kim I. Tetrahedron 2014; 70: 7534
• 31 Grosse S. Mathieu V. Pillard C. Massip S. Marchivie M. Jarry C. Bernard P. Kiss R. Guillaumet G. Eur. J. Med. Chem. 2014; 84: 718
• 32 Grosse S. Pillard C. Massip S. Léger JM. Jarry C. Bourg S. Bernard P. Guillaumet G. Chem. Eur. J. 2012; 18: 14943
• 33 Grosse S. Pillard C. Bernard P. Guillaumet G. Synlett 2013; 24: 2095
• 34a Spitzer WA. Victor F. Pollock GD. Hayes JS. J. Med. Chem. 1988; 31: 1590
• 34b Zhou JP. Ding YW. Zhang HB. Xu L. Dai Y. Chin. Chem. Lett. 2008; 19: 669
• 34c Chen X. Xu W. Wang K. Mo M. Zhang W. Du L. Yuan X. Xu Y. Wang Y. Shen J. J. Med. Chem. 2015; 58: 8529
• 35 Goel R. Luxami V. Paul K. RSC Adv. 2015; 5: 81608 ; and references cited therein
• 36 Li W. Nelson DP. Jensen MS. Hoerrner RS. Javadi GJ. Cai D. Larsen RD. Org. Lett. 2003; 5: 4835
• 37 Parisien M. Valette D. Fagnou K. J. Org. Chem. 2005; 70: 7578
• 38 Liégault B. Lapointe D. Caron L. Vlassova A. Fagnou K. J. Org. Chem. 2009; 74: 1826
• 39 Ermolat’ev DS. Giménez VN. Babaev EV. Van der Eycken E. J. Comb. Chem. 2006; 8: 659
• 40 Lapointe D. Markiewicz T. Whipp CJ. Toderian A. Fagnou K. J. Org. Chem. 2011; 76: 749
• 41 Wang H. Chen C. Huang Z. Yao L. Li B. Peng J. Synthesis 2015; 47: 2457
• 42 Jensen MS. Hoerrner RS. Li W. Nelson DP. Javadi GJ. Dormer PG. Cai D. Larsen RD. J. Org. Chem. 2005; 70: 6034
• 43 Cameron M. Foster BS. Lynch JE. Shi Y.-J. Dolling U.-H. Org. Process Res. Dev. 2006; 10: 398
• 44 Frei R. Breitbach AS. Blackwell HE. Angew. Chem. Int. Ed. 2012; 51: 5226
• 45 Chaudhary V. Venghateri JB. Dhaked HP. S. Bhoyar AS. Guchhait SK. Panda D. J. Med. Chem. 2016; 59: 3439
• 46a Bouloc N. Large JM. Kosmopoulou M. Sun C. Faisal A. Matteucci M. Reynisson J. Brown N. Atrash B. Blagg J. McDonald E. Linardopoulos S. Bayliss R. Bavetsias V. Bioorg. Med. Chem. Lett. 2010; 20: 5988
• 46b Matthews TP. McHardy T. Klair S. Boxall K. Fisher M. Cherry M. Allen CE. Addison GJ. Ellard J. Aherne GW. Westwood IM. van Montfort R. Garrett MD. Reader JC. Collins I. Bioorg. Med. Chem. Lett. 2010; 20: 4045
• 47 Sayer JR. Walldén K. Pesnot T. Campbell F. Gane PJ. Simone M. Koss H. Buelens F. Boyle TP. Selwood DL. Waksman G. Tabor AB. Bioorg. Med. Chem. 2014; 22: 6459
• 48 Hyodo I. Tobisu M. Chatani N. Chem. Asian J. 2012; 7: 1357
• 49 Guchhait SK. Kandekar S. Kashyap M. Taxak N. Bharatam PV. J. Org. Chem. 2012; 77: 8321
• 50 Gembus V. Bonfanti J.-F. Querolle O. Jubault P. Levacher V. Hoarau C. Org. Lett. 2012; 14: 6012
• 51 Johnson BM. Huestis MP. Eur. J. Org. Chem. 2014; 1589
• 52 Marchand P. Bazin M.-A. Pagniez F. Rivière G. Bodero L. Marhadour S. Nourrisson M.-R. Picot C. Ruchaud S. Bach S. Baratte B. Sauvain M. Pareja DC. Vaisberg AJ. Le Pape P. Eur. J. Med. Chem. 2015; 103: 381
• 53 Wang J.-X. McCubbin JA. Jin M. Laufer RS. Mao Y. Crew AP. Mulvihill MJ. Snieckus V. Org. Lett. 2008; 10: 2923
• 54a Byth KF. Cooper N. Culshaw JD. Heaton DW. Oakes SE. Minshull CA. Norman RA. Pauptit RA. Tucker JA. Breed J. Pannifer A. Rowsell S. Stanway JJ. Valentine AL. Thomas AP. Bioorg. Med. Chem. Lett. 2004; 14: 2249
• 54b Pogacic V. Bullock AN. Fedorov O. Filippakopoulos P. Gasser C. Biondi A. Meyer-Monard S. Knapp S. Schwaller J. Cancer Res. 2007; 67: 6916
• 54c Kusakabe K.-i. Ide N. Daigo Y. Itoh T. Yamamoto T. Hashizume H. Nozu K. Yoshida H. Tadano G. Tagashira S. Higashino K. Okano Y. Sato Y. Inoue M. Iguchi M. Kanazawa T. Ishioka Y. Dohi K. Kido Y. Sakamoto S. Ando S. Maeda M. Higaki M. Baba Y. Nakamura Y. J. Med. Chem. 2015; 58: 1760
• 55 El Akkaoui A. Berteina-Raboin S. Mouaddib A. Guillaumet G. Eur. J. Org. Chem. 2010; 862
• 56 Chikhi S. Djebbar S. Soulé J.-F. Doucet H. Chem. Asian J. 2016; 11: 2443
• 57 Meegalla SK. Huang H. Illig CR. Parks DJ. Chen J. Lee Y.-K. Wilson KJ. Patel SK. Cheung WS. Lu T. Kirchner T. Askari HB. Geisler J. Patch RJ. Gibbs AC. Rady B. Connelly M. Player MR. Bioorg. Med. Chem. Lett. 2016; 26: 4216
• 58a Bavetsias V. Large JM. Sun C. Bouloc N. Kosmopoulou M. Matteucci M. Wilsher NE. Martins V. Reynisson J. Atrash B. Faisal A. Urban F. Valenti M. de Haven Brandon A. Box G. Raynaud FI. Workman P. Eccles SA. Bayliss R. Blagg J. Linardopoulos S. McDonald E. J. Med. Chem. 2010; 53: 5213
• 58b Chen D. Wang Y. Ma Y. Xiong B. Ai J. Chen Y. Geng M. Shen J. ChemMedChem 2012; 7: 1057
• 59 Futatsugi K. Kung DW. Orr ST. M. Cabral S. Hepworth D. Aspnes G. Bader S. Bian J. Boehm M. Carpino PA. Coffey SB. Dowling MS. Herr M. Jiao W. Lavergne SY. Li Q. Clark RW. Erion DM. Kou K. Lee K. Pabst BA. Perez SM. Purkal J. Jorgensen CC. Goosen TC. Gosset JR. Niosi M. Pettersen JC. Pfefferkorn JA. Ahn K. Goodwin B. J. Med. Chem. 2015; 58: 7173
• 60a Tatipaka HB. Gillespie JR. Chatterjee AK. Norcross NR. Hulverson MA. Ranade RM. Nagendar P. Creason SA. McQueen J. Duster NA. Nagle A. Supek F. Molteni V. Wenzler T. Brun R. Glynne R. Buckner FS. Gelb MH. J. Med. Chem. 2014; 57: 828
• 60b Madaiah M. Prashanth MK. Revanasiddappa HD. Veeresh B. New J. Chem. 2016; 40: 9194
• 61 Casimiro-Garcia A. Filzen GF. Flynn D. Bigge CF. Chen J. Davis JA. Dudley DA. Edmunds JJ. Esmaeil N. Geyer A. Heemstra RJ. Jalaie M. Ohren JF. Ostroski R. Ellis T. Schaum RP. Stoner C. J. Med. Chem. 2011; 54: 4219
• 62a Onoue S. Igarashi N. Yamauchi Y. Kojima T. Murase N. Zhou Y. Yamada S. Tsuda Y. J. Pharm. Sci. 2008; 97: 4307
• 62b Baladi T. Granzhan A. Piguel S. Eur. J. Org. Chem. 2016; 2421
• 63 Barbero N. SanMartin R. Domínguez E. Org. Biomol. Chem. 2010; 8: 841
• 64 Iaroshenko VO. Ali I. Mkrtchyan S. Semeniuchenko V. Ostrovskyi D. Langer P. Synlett 2012; 23: 2603
• 65 Iaroshenko VO. Ostrovskyi D. Miliutina M. Maalik A. Villinger A. Tolmachev A. Volochnyuk DM. Langer P. Adv. Synth. Catal. 2012; 354: 2495
• 66 Macdonald J. Oldfield V. Bavetsias V. Blagg J. Org. Biomol. Chem. 2013; 11: 2335
• 67 Avinesh MP. Jaison MT. J. Sajith AM. Nagaswarupa HP. Muralidharan A. ChemistrySelect 2016; 1: 2265
• 68 Aziz J. Baladi T. Piguel S. J. Org. Chem. 2016; 81: 4122
• 69a Howard S. Amin N. Benowitz AB. Chiarparin E. Cui H. Deng X. Heightman TD. Holmes DJ. Hopkins A. Huang J. Jin Q. Kreatsoulas C. Martin AC. L. Massey F. McCloskey L. Mortenson PN. Pathuri P. Tisi D. Williams PA. ACS Med. Chem. Lett. 2013; 4: 1208
• 69b Wang X. Kolesnikov A. Tay S. Chan G. Chao Q. Do S. Drummond J. Ebens AJ. Liu N. Ly J. Harstad E. Hu H. Moffat J. Munugalavadla V. Murray J. Slaga D. Tsui V. Volgraf M. Wallweber H. Chang JH. J. Med. Chem. 2017; 60: 4458
• 70 Ye M. Edmunds AJ. F. Morris JA. Sale D. Zhang Y. Yu J.-Q. Chem. Sci. 2013; 4: 2374
• 71 Egan BA. Burton PM. RSC Adv. 2014; 4: 27726
• 72 Ahmed SA. Elgendy HS. Younes WO. Int. J. Adv. Res. 2014; 2: 474
• 73 Cherukupalli S. Karpoormath R. Chandrasekaran B. Hampannavar GA. Thapliyal N. Palakollu VN. Eur. J. Med. Chem. 2017; 126: 298 ; and references cited therein
• 74 Bassoude I. Berteina-Raboin S. Massip S. Leger J.-M. Jarry C. Essassi EM. Guillaumet G. Eur. J. Org. Chem. 2012; 2572
• 75 Bedford RB. Durrant SJ. Montgomery M. Angew. Chem. Int. Ed. 2015; 54: 8787
• 76 Bassoude I. Tber Z. Essassi EM. Guillaumet G. Berteina-Raboin S. RSC Adv. 2016; 6: 3301
• 77 De Coen LM. Heugebaert TS. A. García D. Stevens CV. Chem. Rev. 2016; 116: 80
• 78 Skardžiūtė L. Kazlauskas K. Dodonova J. Bucevičius J. Tumkevičius S. Juršėnas S. Tetrahedron 2013; 69: 9566
• 79a Klecka M. Pohl R. Klepetarova B. Hocek M. Org. Biomol. Chem. 2009; 7: 866
• 79b Klecka M. Postova Slavetinska L. Hocek M. Eur. J. Org. Chem. 2015; 7943
• 80 Čerňa I. Pohl R. Klepetářová B. Hocek M. Org. Lett. 2006; 8: 5389
• 81 Dodonova J. Tumkevicius S. RSC Adv. 2014; 4: 35966
• 82 Klecka M. Pohl R. Cejka J. Hocek M. Org. Biomol. Chem. 2013; 11: 5189
• 83 Sokolovs I. Lubriks D. Suna E. J. Am. Chem. Soc. 2014; 136: 6920
• 84 Sabat N. Klecka M. Slavetinska L. Klepetarova B. Hocek M. RSC Adv. 2014; 4: 62140
• 85 Sabat N. Poštová Slavětínská L. Klepetářová B. Hocek M. J. Org. Chem. 2016; 81: 9507
• 86 Sabat N. Poštová Slavětínská L. Hocek M. Tetrahedron Lett. 2015; 56: 6860
• 87 Gauthier DR. Limanto J. Devine PN. Desmond RA. Szumigala RH. Foster BS. Volante RP. J. Org. Chem. 2005; 70: 5938
• 88 Ishmetova RI. Ignatenko NK. Belyaninova IA. Tolshchina SG. Korotina AV. Slepukhin PA. Evstigneeva NP. Zil’berberg NV. Amineva PG. Kungurov NV. Rusinov GL. Chupakhin ON. Russ. Chem. Bull. 2015; 64: 2100
• 89 Pellegatti L. Vedrenne E. Leger J.-M. Jarry C. Routier S. J. Comb. Chem. 2010; 12: 604
• 90a Buron F. Mérour JY. Akssira M. Guillaumet G. Routier S. Eur. J. Med. Chem. 2015; 95: 76
• 90b Chauhan M. Kumar R. Bioorg. Med. Chem. 2013; 21: 5657
• 90c Demmer CS. Jørgensen M. Kehler J. Bunch L. Rasmussen LK. Synlett 2015; 26: 519