Palladium(0)-Catalyzed Dearomatization of 2-Nitrobenzofurans through Formal (3+2) Cycloadditions with Vinylcyclopropanes: A Straightforward Access to Cyclopenta[b]benzofurans

Dedicated to Professor Miguel Yus on the occasion of his 70^th birthday.

Abstract

In the context of the palladium-catalyzed dearomatization of electron-poor arenes, we report herein that various 2-nitrobenzofurans efficiently undergo a dearomative (3+2) cycloaddition with vinylcyclopropanes. This new method gives access to a wide variety of cyclo­penta[b]benzofuran derivatives in a straightforward manner.

Key words

dearomatization - palladium(0) catalysis - (3+2) cycloaddition - nitrobenzofurans - vinylcyclopropanes - cyclopenta[b]benzofurans

• References and Notes


For reviews, see:
• 1a Roche SP. Porco JA. Angew. Chem. Int. Ed. 2011; 50: 4068
• 1b Pigge FC. Dearomatization Reactions: An Overview, In Arene Chemistry: Reaction Mechanisms and Methods for Aromatic Compounds. 1st ed. Mortier J. Wiley-VCH; New York: 2016

For reviews, see:
• 2a Zhuo CX. Zhang W. You SL. Angew. Chem. Int. Ed. 2012; 51: 12662
• 2b Ding Q. Zhou X. Fan R. Org. Biomol. Chem. 2014; 12: 4807
• 2c Wu W.-T. Zhang L. You S.-L. Chem. Soc. Rev. 2016; 45: 1570
• 2d Zheng C. You SL. Chem 2016; 1: 830
• 2e Asymmetric Dearomatization Reactions . You S.-L. Wiley-VCH; Weinheim: 2016. For selected examples, see
• 2f Wu QF. He H. Liu WB. You SL. J. Am. Chem. Soc. 2010; 132: 11418
• 2g Wu QF. Liu WB. Zhuo CX. Rong ZQ. Ye KY. You SL. Angew. Chem. Int. Ed. 2011; 50: 4455
• 2h Shibuya T. Noguchi K. Tanaka K. Angew. Chem. Int. Ed. 2012; 51: 6219
• 2i Zhu S. MacMillan DW. C. J. Am. Chem. Soc. 2012; 134: 10815
• 2j Nan J. Zuo Z. Luo L. Bai L. Zheng H. Yuan Y. Liu J. Luan X. Wang Y. J. Am. Chem. Soc. 2013; 135: 17306
• 2k Xiong H. Xu H. Liao S. Xie Z. Tang Y. J. Am. Chem. Soc. 2013; 135: 7851
• 2l Spangler JE. Davies HM. L. J. Am. Chem. Soc. 2013; 135: 6802
• 2m Zhang X. Yang Z.-P. Liu C. You S.-L. Chem. Sci. 2013; 4: 3239
• 2n Tong MC. Chen X. Li J. Huang R. Tao H. Wang CJ. Angew. Chem. Int. Ed. 2014; 53: 4680
• 2o Zi W. Wu H. Toste FD. J. Am. Chem. Soc. 2015; 137: 3225
• 2p Yang D. Wang L. Han F. Li D. Zhao D. Wang R. Angew. Chem. Int. Ed. 2015; 54: 2185
• 2q Li Z. Shi Y. Org. Lett. 2015; 17: 5752

For representative examples, see:
• 3a Kimura M. Futamata M. Mukai R. Tamaru Y. J. Am. Chem. Soc. 2005; 127: 4592
• 3b Trost BM. Quancard J. J. Am. Chem. Soc. 2006; 128: 6314
• 3c García-Fortanet J. Kessler F. Buchwald SL. J. Am. Chem. Soc. 2009; 131: 6676
• 3d Rousseaux S. García-Fortanet J. Del Aguila Sanchez MA. Buchwald SL. J. Am. Chem. Soc. 2011; 133: 9282
• 3e Wu KJ. Dai LX. You SL. Org. Lett. 2012; 14: 3772
• 3f Nemoto T. Zhao Z. Yokosaka T. Suzuki Y. Wu R. Hamada Y. Angew. Chem. Int. Ed. 2013; 52: 2217
• 3g Xiao Q. Jackson JJ. Basak A. Bowler JM. Miller BG. Zakarian A. Nat. Chem. 2013; 5: 410
• 3h Xu Q.-L. Dai L.-X. You S.-L. Chem. Sci. 2013; 4: 97
• 4a Trost BM. Ehmke V. O’Keefe BM. Bringley DA. J. Am. Chem. Soc. 2014; 136: 8213
• 4b Laugeois M. Ling J. Férard C. Michelet V. Ratovelomanana-Vidal V. Vitale MR. Org. Lett. 2017; 19: 2266
• 4c Rivinoja DJ. Gee YS. Gardiner MG. Ryan JH. Hyland CJ. T. ACS Catal. 2017; 7: 1053
• 4d During the preparation of this manuscript, other palladium-catalyzed dearomative (3+2) cycloadditions of nitroaromatics have been described. For 2-nitrobenzofurans, see: Cheng Q. Zhang H.-J. Yue W.-J. You S.-L. Chem 2017; 3: 428
• 4e For 3-nitroindoles, see: Gee YS. Rivinoja DJ. Wales SM. Gardiner MG. Ryan JH. Hyland CJ. T. J. Org. Chem. 2017; 82: 13517

For seminal works on the dearomatization of nitroarenes, see:
• 5a Roy S. Kishbaugh TL. S. Jasinski JP. Gribble GW. Tetrahedron Lett. 2007; 48: 1313
• 5b Lee S. Chataigner I. Piettre SR. Angew. Chem. Int. Ed. 2011; 50: 472
• 5c Lee S. Diab S. Queval P. Sebban M. Chataigner I. Piettre SR. Chem. Eur. J. 2013; 19: 7181

For recent reviews on the reactivity of vinylcyclopropanes, see:
• 6a Ganesh V. Chandrasekaran S. Synthesis 2016; 48: 4347
• 6b Meazza M. Guo H. Rios R. Org. Biomol. Chem. 2017; 15: 2479
• 7 King ML. Chiang C.-C. Ling H.-C. Fujita E. Ochiai M. McPhail AT. J. Chem. Soc., Chem. Commun. 1982; 1150

For recent reviews on the preparation and biological activities of cyclopenta[b]benzofuran-containing compounds, see:
• 8a Kim S. Salim AA. Swanson SM. Kinghorn AD. Anticancer Agents Med. Chem. 2006; 6: 319
• 8b Ribeiro N. Thuaud F. Nebigil C. Désaubry L. Bioorg. Med. Chem. 2012; 20: 1857
• 8c Zhao Q. Abou-Hamdan H. Désaubry L. Eur. J. Org. Chem. 2016; 5908

For selected examples, see:
• 9a Davey AE. Taylor RJ. K. J. Chem. Soc., Chem. Commun. 1987; 25
• 9b Trost BM. Greenspan PD. Yang BV. Saulnier MG. J. Am. Chem. Soc. 1990; 112: 9022
• 9c Gerard B. Cencic R. Pelletier J. Porco JA. Angew. Chem. Int. Ed. 2007; 46: 7831
• 9d El Sous M. Khoo ML. Holloway G. Owen D. Scammells PJ. Rizzacasa MA. Angew. Chem. Int. Ed. 2007; 46: 7835
• 9e Malona JA. Cariou K. Frontier AJ. J. Am. Chem. Soc. 2009; 131: 7560
• 9f Magnus P. Freund WA. Moorhead EJ. Rainey T. J. Am. Chem. Soc. 2012; 134: 6140
• 9g Stone SD. Lajkiewicz NJ. Whitesell L. Hilmy A. Porco JA. J. Am. Chem. Soc. 2015; 137: 525
• 9h Zhou Z. Tius MA. Angew. Chem. Int. Ed. 2015; 54: 6037
• 9i Paz BM. Li Y. Thøgersen MK. Jørgensen KA. Chem. Sci. 2017; 8: 8086

For alternative dearomatization of benzofurans leading to cyclopenta[b]benzofurans, see:
• 10a Saito K. Ishihara H. Kagabu S. Bull. Chem. Soc. Jpn. 1987; 60: 4141
• 10b Fujita M. Oshima M. Okuno S. Sugimura T. Okuyama T. Org. Lett. 2006; 8: 4113
• 10c Qu J.-P. Liang Y. Xu H. Sun X.-L. Yu Z.-X. Tang Y. Chem. Eur. J. 2012; 18: 2196
• 10d Pérez-Vázquez J. Veiga AX. Prado G. Sardina FJ. Paleo MR. Eur. J. Org. Chem. 2012; 975
• 11 Tromelin A. Demerseman P. Royer R. Synthesis 1985; 1074
• 12a Lishanskii IS. Semenova LS. Polym. Sci. U.S.S.R. 1971; 13: 2657
• 12b Suzuki M. Sawada S. Saegusa T. Macromolecules 1989; 22: 1505
• 12c Suzuki M. Sawada S. Yoshida S. Eberhardt A. Saegusa T. Macromolecules 1993; 26: 4748
• 13 The relative stereochemistry of the major diastereoisomer of 3ae could not be established unambiguously by NOESY NMR experiments (see the Supporting Information).
• 14 Lyubchanskaya VM. Chernov GS. Granik VG. Chem. Hetero­cycl. Compd. 1989; 25: 589
• 15 Palladium-Catalyzed (3+2) Dearomatization of 2-Nitrobenzofurans with VCPs; General ProcedureIn a screw-capped vial, vinylcyclopropane (0.44 mmol, 1.1 equiv), 2-nitrobenzofuran (0.40 mmol, 1.0 equiv) and CH₂Cl₂ (800 μL) were successively added. The resulting mixture was stirred at r.t. for 5 min before a solution of Pd₂(dba)₃·CHCl₃ (0.01 mmol, 0.025 equiv) and dppe (0.02 mmol, 0.05 equiv) in CH₂Cl₂ (800 μL), previously stirred at r.t. for 25 min, was transferred via cannula. The cannula was washed with an additional aliquot of CH₂Cl₂ (400 μL) (total volume of solvent = 2.0 mL) and the final reaction mixture was stirred at r.t. for 2 h. At this point, CH₂Cl₂ (10 mL) was added, the mixture was loaded onto a small silica plug, eluted with additional CH₂Cl₂ (40 mL) and concentrated under reduced pressure. After measurement of the diastereomeric ratio by ¹H NMR spectroscopy, the resulting crude mixture was purified by flash column chromatography to afford the desired cycloadduct.7-Bromo-3a-nitro-3-vinyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-1,1-dicarbonitrile (3aa)Following the typical procedure, starting from 5-bromo-2-nitrobenzofuran (1a) (97 mg), compound 3aa was obtained as a white solid (126 mg, 88% yield, 1:1 dr) after flash column chromatography (toluene/petroleum ether, 6:4). Mp 162–164 °C; IR (film): 2359, 1560, 1509, 1365, 1313, 1243 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.73–7.45 (m, 4 H), 7.03 (dd, J = 9.0, 5.8 Hz, 2 H), 5.95–5.74 (m, 1 H), 5.74–5.56 (m, 1 H), 5.55–5.32 (m, 4 H), 4.96 (s, 1 H), 4.78 (s, 1 H), 4.10–3.90 (m, 1 H), 3.60–3.39 (m, 1 H), 3.05–2.91 (m, 2 H), 2.87 (ddd, J = 13.5, 5.8, 1.3 Hz, 1 H), 2.36 (t, J = 13.5 Hz, 1 H); ¹³C NMR (101 MHz, CDCl₃): δ = 157.9, 157.6, 135.7, 135.4, 130.1, 128.1, 128.0, 127.6, 124.0, 123.5, 123.4, 121.8, 121.7, 121.2, 116.9, 116.6, 114.4, 113.5, 113.4, 112.7, 111.9, 111.6, 63.0, 60.4, 52.4, 51.3, 43.3, 41.1, 39.7, 38.5; MS (EI): m/z = 312 [M – HNO₂]^+•.