Synthesis, Table of Contents Synthesis 2020; 52(15): 2245-2258DOI: 10.1055/s-0039-1690881 paper © Georg Thieme Verlag Stuttgart · New YorkBX3-Mediated Intermolecular Formation of Functionalized 3-Halo-1H-indenes via Cascade Halo-Nazarov-Type Cyclization Authors Author Affiliations Anupama Kumari Rodney A. Fernandes ∗ Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, Maharashtra, India Email: rfernand@chem.iitb.ac.in Recommend Article Abstract All articles of this category(opens in new window) Abstract A BX3-promoted, intermolecular regioselective synthesis of 3-halo-functionalized 1H-indenes from 4-oxo-4H-chromene-3-carbaldehydes and alkynes has been developed. BX3 displays a dual role of Lewis acid catalyst and halide source for haloallyl cation formation for the intended halo-Nazarov-type cyclization. The overall transformation represents an efficient cascade annulation that employs readily available starting materials, inexpensive reagents and a convenient and mild reaction procedure to generate halo-functionalized indenes (45 examples). The reaction was also extended to 8-formylcoumarins to deliver coumarin-based 3-halo-1H-indenes in 79–95% yield (6 examples). The reaction involves conversion of the aldehyde into an sp3 carbon with two new C–C bonds and additionally a C–X bond is formed (X = halide). Key words Key wordsLewis acids - Nazarov cyclization - hybrid structures - C–C bond formation - electrocyclic reactions Full Text References References For examples, see: 1a Adesanya SA, Nia R, Martin M.-T, Boukamcha N, Montagnac A, Païs M. J. Nat. Prod. 1999; 62: 1694 1b Huang K.-S, Wang Y.-H, Li R.-L, Lin M. Phytochemistry 2000; 54: 875 1c Yu H, Kim IJ, Folk JE, Tian X, Rothman RB, Baumann MH, Dersch CM, Flippen-Anderson JL, Parrish D, Jacobson AE, Rice KC. J. Med. Chem. 2004; 47: 2624 1d Clegg NJ, Paruthiyil S, Leitman DC, Scanlan TS. J. Med. Chem. 2005; 48: 5989 1e Majetich G, Shimkus JM. J. Nat. Prod. 2010; 73: 284 1f Liedtke AJ, Crews BC, Daniel CM, Blobaum AL, Kingsley PJ, Ghebreselasie K, Marnett LJ. J. Med. Chem. 2012; 55: 2287 1g Vilums M, Heuberger J, Heitman LH, Ijzerman AP. Med. Res. Rev. 2015; 35: 1097 For examples, see: 2a Dyrager C, Möllers LN, Kjäll LK, Alao JP, Diner P, Wallner FK, Sunnerhagen P, Grøtli M. J. Med. Chem. 2011; 54: 7427 2b Gaspar A, Matos MJ, Garrido J, Uriarte E, Borges F. Chem. Rev. 2014; 114: 4960 2c Keri RS, Budagumpi S, Pai RK, Balakrishna RG. Eur. J. Med. Chem. 2014; 78: 340 2d Silva CF. M, Pinto DC. G. A, Silva AM. S. ChemMedChem. 2016; 11: 2252 2e Reis J, Gaspar A, Milhazes N, Borges F. J. Med. Chem. 2017; 60: 7941 2f Li F, Wu J.-J, Wang J, Yang X.-L, Cai P, Liu Q.-H, Kong L.-Y, Wang X.-B. Bioorg. Med. Chem. 2017; 25: 3815 For examples, see: 3a Meunier B. Acc. Chem. Res. 2008; 41: 69 3b Decker M. Curr. Med. Chem. 2011; 18: 1464 3c Lödige M, Hiersch L. Int. J. Med. Chem. 2015; 3d Bérubé G. Expert Opin. Drug Discovery 2016; 11: 281 3e Agarwal D, Gupta RD, Awasthi SK. Antimicrob. Agents Chemother. 2017; 61: 1 For some informative reviews, see: 4a Denmark SE. Compr. Org. Synth. 1991; 5: 751 4b Santelli-Rouvier C, Santelli M. Synthesis 1983; 429 4c Tius MA. Eur. J. Org. Chem. 2005; 2193 4d Nakanishi W, West FG. Curr. Opin. Drug Discovery Dev. 2009; 12: 732 4e Shimada N, Stewart C, Tius MA. Tetrahedron 2011; 67: 5851 4f Spencer WT. III, Vaidya T, Frontier AJ. Eur. J. Org. Chem. 2013; 3621 4g Di Grandi MJ. Org. Biomol. Chem. 2014; 12: 5331 4h Wenz DR, Read de Alaniz J. Eur. J. Org. Chem. 2015; 23 4i Vinogradov MG, Turova OV, Zlotin SG. Org. Biomol. Chem. 2017; 15: 8245 For examples, see: 5a Weinreb SM, Auerbach J. J. Am. Chem. Soc. 1975; 97: 2503 5b Kim S.-H, Cha JK. Synthesis 2000; 2113 5c Li W.-DZ, Wang Y.-Q. Org. Lett. 2003; 5: 2931 5d He W, Huang J, Sun X, Frontier AJ. J. Am. Chem. Soc. 2007; 129: 498 5e He W, Huang J, Sun X, Frontier AJ. J. Am. Chem. Soc. 2008; 130: 300 5f Williams DR, Robinson LA, Nevill CR, Reddy JP. Angew. Chem. Int. Ed. 2007; 46: 915 5g Bitar AY, Frontier AJ. Org. Lett. 2009; 11: 49 5h Bhattacharya C, Bonfante P, Deagostino A, Kapulnik Y, Larini P, Occhiato EG, Prandi C, Venturello P. Org. Biomol. Chem. 2009; 7: 3413 5i Carlsen PN, Mann TJ, Hoveyda AH, Frontier AJ. Angew. Chem. Int. Ed. 2014; 53: 9334 5j Grant TN, Rieder CJ, West FG. Chem. Commun. 2009; 5676 5k Malona JA, Cariou K, Frontier AJ. J. Am. Chem. Soc. 2009; 131: 7560 5l Churruca F, Fousteris M, Ishikawa Y, von Wantoch Rekowski M, Hounsou C, Surrey T, Giannis A. Org. Lett. 2010; 12: 2096 5m Vaidya T, Eisenberg R, Frontier AJ. ChemCatChem 2011; 3: 1531 5n Magnus P, Freund WA, Moorhead EJ, Rainey T. J. Am. Chem. Soc. 2012; 134: 6140 5o Zhou Z, Tius MA. Angew. Chem. Int. Ed. 2015; 54: 6037 6a Alachouzos G, Frontier AJ. Angew. Chem. Int. Ed. 2017; 56: 15030 6b Alachouzos G, Frontier AJ. J. Am. Chem. Soc. 2019; 141: 118 6c Holt C, Alachouzos G, Frontier AJ. J. Am. Chem. Soc. 2019; 141: 5461 7 Ghavtadze N, Fröhlich R, Bergander K, Würthwein E.-U. Synthesis 2008; 3397 8a Viswanathan GS, Li C.-J. Tetrahedron Lett. 2002; 43: 1613 8b Zhou X, Zhang H, Xie X, Li Y. J. Org. Chem. 2008; 73: 3958 8c Yeh M.-CP, Lin M.-N, Hsu C.-H, Liang C.-J. J. Org. Chem. 2013; 78: 12381 8d Strom KR, Impastato AC, Moy KJ, Landreth AJ, Snyder JK. Org. Lett. 2015; 17: 2126 9a Ye S, Gao K, Zhou H, Yang X, Wu J. Chem. Commun. 2009; 5406 9b Sanz R, Martínez A, García-García P, Fernández-Rodríguez MA, Rashid MA, Rodríguez F. Chem. Commun. 2010; 46: 7427 9c Johansson Seechurn CC. C, Kitching MO, Colacot TJ, Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 5062 10 Sultana S, Maezono SM. B, Akhtar MS, Shim JJ, Wee YJ, Kim SH, Lee YR. Adv. Synth. Catal. 2018; 360: 751 11 CCDC 1945920 (6ae), CCDC 1945839 (6bb), CCDC 1945927 (6bi), CCDC 1945916 (6bm), CCDC 1945936 (6cm), CCDC 1945919 (8e) and CCDC 1946265 (12) contain 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. See the Supporting Information (SI) for structures. 12a He W, Sun X, Frontier AJ. J. Am. Chem. Soc. 2003; 125: 14278 12b Nie J, Zhu H.-W, Cui H.-F, Hua M.-Q, Ma J.-A. Org. Lett. 2007; 9: 3053 12c Xi Z.-G, Zhu L, Luo S, Cheng J.-P. J. Org. Chem. 2013; 78: 606 12d Zhu L, Xi Z.-G, Lv J, Luo S. Org. Lett. 2013; 15: 4496 12e Zhu Y.-P, Cai Q, Jia F.-C, Liu M.-C, Gao Q.-H, Meng X.-G, Wu A.-X. Tetrahedron 2014; 70: 9536 12f Carmichael RA, Sophanpanichkul P, Chalifoux WA. Org. Lett. 2017; 19: 2592 13 During the completion and submission of our work a conceptionally similar paper appeared; see: Sultana S, Lee YR. Adv. Synth. Catal. 2020; 362: 927 14 Dückert H, Khedkar V, Waldmann H, Kumar K. Chem. Eur. J. 2011; 17: 5130 15 Levi ZU, Tilley TD. J. Am. Chem. Soc. 2009; 131: 2796 16 Shairgojray BA, Dar AA, Bhat BA. Tetrahedron Lett. 2013; 54: 2391 17 Adary EM, Chang C.-W, D’ Auria DT, Nguyen PM, Polewacz K, Reinicke JA, Seo H, Berger GO. Tetrahedron Lett. 2015; 56: 386 Supplementary Material Supplementary Material Supporting Information (PDF) (opens in new window)
