Facile Synthesis of [1,2,3]-Triazole-Fused Isoindolines, Tetrahydroisoquino­lines, Benzoazepines and Benzoazocines by Palladium-Copper Catalysed Heterocyclisation­

Abstract

An elegant method for the synthesis of 1,2,3-triazoles fused with five-, six-, seven- and eight-membered benzoheterocycles, including isoindoline, tetrahydroisoquinoline, benzoazepine and benzoazocine, has been developed via palladium-copper catalysed reactions in one-pot. The broad scope of this reaction was illustrated by effecting bis-heteroannulations, synthesis of uracil derivatives of biological interest, and employment of acetylene gas as an inexpensive substrate. The reactions are experimentally simple and utilise easily accessible substrates of different types.

Key words

1,2,3-triazoles - nitrogen heterocycles - intramolecular reactions - azide-alkyne cycloaddition - bis-heteroannulations

• References

• 1a Puig-Basagoiti F, Qing M, Dong H, Zhang B, Zou G, Yuan Z, Shi P.-Y. Antiviral Res. 2009; 83: 71
• 1b Fung-Tomc JC, Huczko E, Minassian B, Bonner DP. Antimicrob. Agents Chemother. 1998; 42: 313
• 1c Maurya SK, Gollapalli DR, Kirubakaran S, Zhang M, Johnson CR, Benjamin NN, Hedstrom L, Cuny GD. J. Med. Chem. 2009; 52: 4623
• 1d Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE, Garmon SA, Graber DR, Grega KC, Hester JB, Hutchinson DK, Morris J, Reischer RJ, Ford CW, Zurenko GE, Hamel JC, Schaadt RD, Stapert D, Yagi BH. J. Med. Chem. 2000; 43: 953
• 1e Lee T, Cho M, Ko S.-Y, Youn H.-J, Baek DJ, Cho W.-J, Kang C.-Y, Kim S. J. Med. Chem. 2007; 50: 585
• 1f For a recent review article, see: Agalave SG, Maujan SR, Pore VS. Chem. Asian J. 2011; 6: 2696
• 2 Holub JM, Kirshenbaum K. Chem. Soc. Rev. 2010; 39: 1325
• 3a Huisgen R. Angew. Chem., Int. Ed. Engl. 1963; 2: 565
• 3b Huisgen R In 1,3-Dipolar Cycloaddition Chemistry . Padwa A. Wiley; New York: 1984: 1-176
• 4a Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596
• 4b Tornoe CW, Christensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
• 5a Kwok SW, Fotsing JR, Fraser RJ, Rodionov VO, Fokin VV. Org. Lett. 2010; 12: 4217
• 5b Zhang L, Chen X, Xue P, Sun HH. Y, Williams ID, Sharpless KB, Fokin VV, Jia G. J. Am. Chem. Soc. 2005; 127: 15998
• 5c Boren BC, Narayan S, Rasmussen LK, Zhang L, Zhao H, Lin Z, Jia G, Fokin VV. J. Am. Chem. Soc. 2008; 130: 8923
• 6a Moses JE, Moorehouse AD. Chem. Soc. Rev. 2007; 36: 1249
• 6b Kolb HC, Sharpless KB. Drug Discovery Today 2003; 8: 1128
• 6c Nandivada H, Jiang X, Lahann J. Adv. Mater. 2007; 19: 2197
• 6d Fournier D, Hoogenboom R, Schubert US. Chem. Soc. Rev. 2007; 36: 1369
• 6e Lutz J.-F. Angew. Chem. Int. Ed. 2007; 46: 1018 ; Angew. Chem. 2007, 119, 1036
• 6f Golas PL, Matyjaszewski K. Chem. Soc. Rev. 2010; 39: 1338
• 7 Ackermann L, Potukuchi HK, Landsberg D, Vicente R. Org. Lett. 2008; 10: 3081
• 8 For a review article, see: Majumdar KC, Ray K. Synthesis 2011; 3767

For biological activities, see:
• 9a Berger D, Citarella R, Dutia M, Greenberger L, Hallett W, Paul R, Powell D. J. Med. Chem. 1999; 42: 2145
• 9b Alanine A, Burner S, Buettelmann B, Heitz NM, Jaeschke G, Pinard E, Wyler R. Eur. Pat. Appl. EP1090917, 2001 ; Chem. Abstr. 2001, 134, 280719b
• 9c Goethem SV, Matheeussen V, Joossens J, Lambeir A.-M, Chen X, Meester ID, Haemers A, Augustyns K, der Veken PV. J. Med. Chem. 2011; 54: 5737

For biological activities, see:
• 10a Scott JD, Williams RM. J. Am. Chem. Soc. 2002; 124: 2951
• 10b Oku N, Matsunaga S, Vaa Soest RW. M, Fusetani N. J. Nat. Prod. 2003; 66: 1136
• 10c Razet R, Thomet U, Furtmuller R, Chiaroni A, Sigel E, Sieghart W, Dodd RH. J. Med. Chem. 2000; 43: 4363
• 10d Allan KM, Stoltz BM. J. Am. Chem. Soc. 2008; 130: 17270

For biological activities, see:
• 11a Malachowski WP, Paul T, Phounsavath S. J. Org. Chem. 2007; 72: 6792
• 11b Evans P, Lee AT. L, Thomas EJ. Org. Biomol. Chem. 2008; 6: 2158
• 11c Takeuchi K, Holloway WG, Mitch CH, Quimby SJ, McKinzie JH, Suter TM, Statnick MA, Surface PL, Emmerson PJ, Thomas EM, Siegel MG. Bioorg. Med. Chem. Lett. 2007; 17: 6841

For biological activities, see:
• 12a Seto M, Aikawa K, Miyamoto N, Aramaki Y, Kanzaki N, Takashima K, Kuze Y, Iizawa Y, Baba M, Shiraishi M. J. Med. Chem. 2006; 49: 2037
• 12b Sofia MJ, Chang W, Furman PA, Mosley RT, Ross BS. J. Med. Chem. 2012; 55: 2481
• 13 Das Adhikary N, Chattopadhyay P. J. Org. Chem. 2012; 77: 5399
• 14 Endo Y, Ohno M, Hirano M, Itai A, Shudo K. J. Am. Chem. Soc. 1996; 118: 1841
• 15a Snyder PJ, Werth J, Giordani B, Caveney AF, Feltner D, Maruff P. Hum. Psychopharmacol. Clin. Exp. 2005; 20: 263
• 15b Greenblatt DJ, Harmatz JS, Shapiro L, Engelhardt N, Gouthro TA, Shader RI. N. Engl. J. Med. 1991; 324: 1691
• 15c Georgiev S, Loev B, Mack R, Musser J. US Patent US 4276292, 1981 ; Chem. Abstr. 1981, 95, 132905v
• 15d Tatsuta K, Ikeda Y, Miura S. J. Antibiot. 1996; 49: 836
• 15e Bromidge SM, Arban R, Bertani B, Bison S, Borriello M, Cavanni P, Dal Forno G, Di-Fabio R, Donati D, Fontana S, Gianotti M, Gordon LJ, Granei E, Leslie CP, Moccia L, Pasquarello A, Sartori I, Sava A, Watson JM, Worby A, Zonzini L, Zucchelli V. J. Med. Chem. 2010; 53: 5827
• 16a Kallander LS, Lu Q, Chen W, Tomaszek T, Yang G, Tew D, Meek TD, Hoffmann GA, Schulz-Pritchard CK, Smith WW, Janson CA, Ryan MD, Zhang G.-F, Johanson KO, Kirkpatrick RB, Ho TF, Fisher PW, Mattern MR, Johnson RK, Hansbury MJ, Winkler JD, Ward KW, Veber DF, Thompson SK. J. Med. Chem. 2005; 48: 5644
• 16b Niculescu-Duvaz D, Niculescu-Duvaz I, Suijkerbuijk BM. J. M, Menard D, Zambon A, Nourry A, Davies L, Manne HA, Friedlos F, Ogilvie L, Hedley D, Takle AK, Wilson DM, Pons J.-F, Coulter T, Kirk R, Cantarino N, Whittaker S, Marais R, Springer CJ. Bioorg. Med. Chem. 2010; 18: 6934
• 17a Chuprakov S, Chernyak N, Dudnik AS, Gevorgyan V. Org. Lett. 2007; 9: 2333
• 17b Ackermann L, Vicente R, Born R. Adv. Synth. Catal. 2008; 350: 741
• 17c Ackermann L, Jeyachandran R, Potukuchi HK, Novak P, Buttner L. Org. Lett. 2010; 12: 2056
• 17d Fiandanese V, Marchese G, Punzi A, Iannone F, Rafaschieri GG. Tetrahedron 2010; 66: 8846
• 17e Schulman JM, Friedman AA, Panteleev J, Lautens M. Chem. Commun. 2012; 48: 55

For a recent review article, see ref. 8. For examples, see:
• 18a Conrad WE, Rodriguez KX, Nguyen HH, Fettinger JC, Haddadin MJ, Kurth MJ. Org. Lett. 2012; 14: 3870
• 18b Arigela RK, Mandadapu AK, Sharma SK, Kumar B, Kundu B. Org. Lett. 2012; 14: 1804
• 18c Hu Y.-Y, Wang X.-C, Guo L.-N, Shu X.-Z, Niu Y.-N, Liang Y.-M. Tetrahedron 2010; 66: 80
• 19a Chowdhury C, Mukherjee S, Das B, Achari B. J. Org. Chem. 2009; 74: 3612
• 19b Chowdhury C, Sasmal AK, Dutta PK. Tetrahedron Lett. 2009; 50: 2678
• 19c Chowdhury C, Sasmal AK, Achari B. Org. Biomol. Chem. 2010; 8: 4971
• 19d Chowdhury C, Mukherjee S, Chakraborty B, Achari B. Org. Biomol. Chem. 2011; 9: 5856
• 20 For a preliminary communication, see: Chowdhury C, Mandal SB, Achari B. Tetrahedron Lett. 2005; 46: 8531
• 21a Ripa L, Hallberg A. J. Org. Chem. 1996; 61: 7147
• 21b Tummatorn J, Dudley GB. Org. Lett. 2011; 13: 1572
• 22a Heidelberger C. Pyrimidine and Pyrimidine Antimetabolites in Cancer Medicines . Holland JF, Frei E. Lea and Febiger; Philadelphia: 1984: 801
• 22b Onishi T, Mukai C, Nakagawa R, Sekiyama T, Aoki M, Suzuki K, Nakazawa H, Ono N, Ohmura Y, Iwayama S, Okunishi M, Tsuji T. J. Med. Chem. 2000; 43: 278 ; and references cited therein
• 23a Das B, Chowdhury C, Kumar D, Sen R, Roy R, Das P, Chatterjee M. Bioorg. Med. Chem. Lett. 2010; 20: 6947
• 23b Srivastava V, Darokar MP, Fatima A, Kumar JK, Chowdhury C, Saxena HO, Dwivedi GR, Shrivastava K, Gupta V, Chattopadhyay SK, Luqman S, Gupta MM, Negi AS, Khanuja SP. S. Bioorg. Med. Chem. 2007; 15: 518
• 24 Cytotoxicities of compounds 11a and 11b against various cancer cell lines are currently under study.
• 25 Based on control experiments and known features of palladium chemistry, a plausible reaction mechanism can be envisaged. Mechanistically, the active catalytic species Pd(0) is generated in situ by dimerization, to a small extent, of acetylenic compound 8. Next, coupling of 8 with iodide 7 takes place through the Sonogashira pathway, see: Sonogashira K, Tohda Y, Haghihara N. Tetrahedron Lett. 1975; 50: 4467 ; leading to the formation of intermediate o-alkynyl azide derivative, which is then converted into products 1–4 through intramolecular [3+2] cycloaddition between azide and alkyne moieties. An alternative mechanism involving copper-assisted regioselective [3+2] cycloaddition between acetylene and azide groups of substrates 8 and 7, leading to the formation of intermediate 1,4-substituted 1,2,3-triazoles 9 (X = I), which may undergo intramolecular coupling with aryl iodide through C–H bond activation to form the products 1–4, was ruled out on the basis of control experiments