Highly Efficient Synthesis of N ¹-Substituted 1H-Indazoles by DBU-Catalyzed Aza-Michael Reaction of Indazole with Enones

Abstract

1H-Indazoles are important heterocycles as they are a substantial part in many drugs. Here, a DBU-catalyzed aza-Michael reaction of indazole with enones is described. A variety of aromatic and aliphatic enones are well tolerated and afford the corresponding N ¹-substituted 1H-indazoles in high to excellent yields with exclusive N ¹-regioselectivity. The use of a metal-free catalyst, good substrate tolerance, mild reaction conditions, and high atom economy make this procedure a direct and facile method for the preparation of N ¹-substituted 1H-indazoles.

Key words

Michael addition - indazoles - enones - catalysis - regioselectivity

• References


For selected reviews, see:
• 1a Amara Z, Caron J, Joseph D. Nat. Prod. Rep. 2013; 30: 1211
• 1b Weiner B, Szymański W, Janssen DB, Minnaard AJ, Feringa BL. Chem. Soc. Rev. 2010; 39: 1656
• 1c Mikami K, Fustero S, Sánchez-Roselló M, Aceña JL, Soloshonok V, Sorochinsky A. Synthesis 2011; 3045
• 1d Cardillo G, Tomasini C. Chem. Soc. Rev. 1996; 25: 117

For selected reviews, see:
• 2a Sánchez-Roselló M, Aceña JL, Simón-Fuentes A, del Pozo C. Chem. Soc. Rev. 2014; 43: 7430
• 2b Wang J, Li P, Choy PY, Chan AS. C, Kwong FY. ChemCatChem 2012; 4: 917
• 2c Enders D, Wang C, Liebich JX. Chem. Eur. J. 2009; 15: 11058
• 2d Xu L.-W, Xia C.-G. Eur. J. Org. Chem. 2005; 633
• 3a Gandelman M, Jacobsen EN. Angew. Chem. Int. Ed. 2005; 44: 2393
• 3b Wang J, Li H, Zu L, Wang W. Org. Lett. 2006; 8: 1391
• 3c Dinér P, Nielsen M, Marigo M, Jørgensen KA. Angew. Chem. Int. Ed. 2007; 46: 1983
• 3d Uria U, Vicario JL, Badía D, Carrillo L. Chem. Commun. 2007; 2509
• 3e Liu BK, Wu Q, Qian XQ, Lv DS, Lin XF. Synthesis 2007; 2653
• 3f Xu J.-M, Qian C, Liu B.-K, Wu Q, Lin X.-F. Tetrahedron 2007; 63: 986
• 3g Wang J, Zu L, Li H, Xie H, Wang W. Synthesis 2007; 2576
• 3h Lin Q, Meloni D, Pan Y, Xia M, Rodgers J, Shepard S, Li M, Galya L, Metcalf B, Yue T.-Y, Liu P, Zhou J. Org. Lett. 2009; 11: 1999
• 3i Luo GS, Zhang SL, Duan WH, Wang W. Synthesis 2009; 1564
• 3j Cai Q, Zheng C, You S.-L. Angew. Chem. Int. Ed. 2010; 49: 8666
• 3k Lv J, Wu H, Wang Y. Eur. J. Org. Chem. 2010; 2073
• 3l Guo H.-M, Yuan T.-F, Niu H.-Y, Liu J.-Y, Mao R.-Z, Li D.-Y, Qu G.-R. Chem. Eur. J. 2011; 17: 4095
• 3m Lee S.-J, Youn S.-H, Cho C.-W. Org. Biomol. Chem. 2011; 9: 7734
• 3n Li H, Zhao J, Zeng L, Hu W. J. Org. Chem. 2011; 76: 8064
• 3o Uria U, Reyes E, Vicario JL, Badía D, Carrillo L. Org. Lett. 2011; 13: 336
• 3p Wang J, Wang W, Liu X, Hou Z, Lin L, Feng X. Eur. J. Org. Chem. 2011; 2039
• 3q Wu H, Tian Z, Zhang L, Huang Y, Wang Y. Adv. Synth. Catal. 2012; 354: 2977
• 3r Wang J, Li P.-F, Chan SH, Chan AS. C, Kwong FY. Tetrahedron Lett. 2012; 53: 2887
• 3s Wu Y, Wang J, Li P, Kwong FY. Synlett 2012; 23: 788
• 3t Xie S.-L, Hui Y.-H, Long X.-J, Wang C.-C, Xie Z.-F. Chin. Chem. Lett. 2013; 24: 28
• 3u Lee S.-J, Ahn J.-G, Cho C.-W. Tetrahedron: Asymmetry 2014; 25: 1383
• 3v Li P, Fang F, Chen J, Wang J. Tetrahedron: Asymmetry 2014; 25: 98
• 3w Zhang J, Zhang Y, Liu X, Guo J, Cao W, Lin L, Feng X. Adv. Synth. Catal. 2014; 356: 3545
• 3x Yang J, Ma B, Zhou H, Zhan B, Li Z. Chin. J. Org. Chem. 2015; 35: 121
• 3y Chen S.-W, Zhang G.-C, Lou Q.-X, Cui W, Zhang S.-S, Hu W.-H, Zhao J.-L. ChemCatChem 2015; 7: 1935

For reviews, see:
• 4a Gaikwad DD, Chapolikar AD, Devkate CG, Warad KD, Tayade AP, Pawar RP, Domb AJ. Eur. J. Med. Chem. 2015; 90: 707
• 4b Schmidt A, Beutler A, Snovydovych B. Eur. J. Org. Chem. 2008; 4073
• 4c Ali NA. S, Dar BA, Pradhan V, Farooqui M. Mini-Rev. Med. Chem. 2013; 13: 1792
• 4d Aguilera-Venegas B, Olea-Azar C, Arán VJ, Speisky H. Future Med. Chem. 2013; 5: 1843
• 4e Thangadurai A, Minu M, Wakode S, Agrawal S, Narasimhan B. Med. Chem. Res. 2012; 21: 1509
• 4f Cerecetto H, Gerpe A, Gonzalez M, Aran VJ, de Ocariz CO. Mini-Rev. Med. Chem. 2005; 5: 869

For recent examples, see:
• 5a Wang H.-L, Cee VJ, Chavez FJr, Lanman BA, Reed AB, Wu B, Guerrero N, Lipford JR, Sastri C, Winston J, Andrews KL, Huang X, Lee MR, Mohr C, Xu Y, Zhou Y, Tasker AS. Bioorg. Med. Chem. Lett. 2015; 25: 834
• 5b Wada Y, Shirahashi H, Iwanami T, Ogawa M, Nakano S, Morimoto A, Kasahara K.-i, Tanaka E, Takada Y, Ohashi S, Mori M, Shuto S. J. Med. Chem. 2015; 58: 6048
• 5c Liu Y, Lang Y, Patel NK, Ng G, Laufer R, Li S.-W, Edwards L, Forrest B, Sampson PB, Feher M, Ban F, Awrey DE, Beletskaya I, Mao G, Hodgson R, Plotnikova O, Qiu W, Chirgadze NY, Mason JM, Wei X, Lin DC.-C, Che Y, Kiarash R, Madeira B, Fletcher GC, Mak TW, Bray MR, Pauls HW. J. Med. Chem. 2015; 58: 3366
• 5d Liu J, Peng X, Dai Y, Zhang W, Ren S, Ai J, Geng M, Li Y. Org. Biomol. Chem. 2015; 13: 7643
• 5e Hummel JR, Ellman JA. J. Am. Chem. Soc. 2015; 137: 490
• 5f Rooney L, Vidal A, D’Souza A.-M, Devereux N, Masick B, Boissel V, West R, Head V, Stringer R, Lao J, Petrus MJ, Patapoutian A, Nash M, Stoakley N, Panesar M, Verkuyl JM, Schumacher AM, Petrassi HM, Tully DC. J. Med. Chem. 2014; 57: 5129
• 5g Naas M, El Kazzouli S, Essassi EM, Bousmina M, Guillaumet G. J. Org. Chem. 2014; 79: 7286
• 5h Liu Z, Wang L, Tan H, Zhou S, Fu T, Xia Y, Zhang Y, Wang J. Chem. Commun. 2014; 50: 5061
• 5i Fang Y, Wang C, Su S, Yu H, Huang Y. Org. Biomol. Chem. 2014; 12: 1061
• 5j Lian Y, Bergman RG, Lavis LD, Ellman JA. J. Am. Chem. Soc. 2013; 135: 7122
• 6 Guan Z, Namyslo JC, Drafz MH. H, Nieger M, Schmidt A. Beilstein J. Org. Chem. 2014; 10: 832
• 7a Kim S.-H, Markovitz B, Trovato R, Murphy BR, Austin H, Willardsen AJ, Baichwal V, Morham S, Bajji A. Bioorg. Med. Chem. Lett. 2013; 23: 2888
• 7b Shi J.-J, Ji F.-H, He P.-L, Yang Y.-X, Tang W, Zuo J.-P, Li Y.-C. ChemMedChem 2013; 8: 722
• 7c Lone SH, Bhat KA, Shakeel-u-Rehman, Majeed R, Hamid A, Khuroo MA. Bioorg. Med. Chem. Lett. 2013; 23: 4931
• 7d Wilks A, Mackerell AD. Jr, Lopes P, Furci LM. PCT Int. Appl WO2008014266, 2008 ; Chem. Abstr. 2008, 148, 138891.
• 7e Aissaoui H, Boss C, Valdenaire A, Pothier J, Richard-Bildstein S, Risch P, Siegrist R. PCT Int. Appl WO2012004722, 2012 ; Chem. Abstr. 2012, 156, 175131.

For recent examples, see:
• 8a Yu J, Lim JW, Kim SY, Kim J, Kim JN. Tetrahedron Lett. 2015; 56: 1432
• 8b Nordmann J, Eierhoff S, Denißen M, Mayer B, Müller TJ. J. Eur. J. Org. Chem. 2015; 5128
• 8c Kashiwa M, Sonoda M, Tanimori S. Eur. J. Org. Chem. 2014; 4720
• 8d Han S, Shin Y, Sharma S, Mishra NK, Park J, Kim M, Kim M, Jang J, Kim IS. Org. Lett. 2014; 16: 2494
• 8e Esmaeili-Marandi F, Saeedi M, Mahdavi M, Yavari I, Foroumadi A, Shafiee A. Synlett 2014; 25: 2605
• 8f Dubost E, Stiebing S, Ferrary T, Cailly T, Fabis F, Collot V. Tetrahedron 2014; 70: 8413
• 8g Chen J, Chen P, Song C, Zhu J. Chem. Eur. J. 2014; 20: 14245
• 8h Yu D.-G, Suri M, Glorius F. J. Am. Chem. Soc. 2013; 135: 8802
• 8i Thomé I, Besson C, Kleine T, Bolm C. Angew. Chem. Int. Ed. 2013; 52: 7509
• 8j Liu H.-J, Hung S.-F, Chen C.-L, Lin M.-H. Tetrahedron 2013; 69: 3907
• 9 De la Cruz A, Elguero J, Goya P, Martinez A. J. Heterocycl. Chem. 1988; 25: 225
• 10 Skidmore J, Heer J, Johnson CN, Norton D, Redshaw S, Sweeting J, Hurst D, Cridland A, Vesey D, Wall I, Ahmed M, Rivers D, Myatt J, Giblin G, Philpott K, Kumar U, Stevens A, Bit RA, Haynes A, Taylor S, Watson R, Witherington J, Demont E, Heightman TD. J. Med. Chem. 2014; 57: 10424
• 11 Teixeira FC, Lucas C, Curto MJ. M, Teixeira AP. S, Duarte MT, André V. Heteroat. Chem. 2016; in press; DOI: 10.1002/hc.21282
• 12 Moran J, Dornan P, Beauchemin AM. Org. Lett. 2007; 9: 3893
• 13 Han X. Tetrahedron Lett. 2007; 48: 2845
• 14 Bhanuchandra M, Kuram MR, Sahoo AK. Org. Biomol. Chem. 2012; 10: 3538
• 15 CCDC 1428774 (compound 2s) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.