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DOI: 10.1055/s-0036-1591540
Palladium(0)-Catalyzed Dearomatization of 2-Nitrobenzofurans through Formal (3+2) Cycloadditions with Vinylcyclopropanes: A Straightforward Access to Cyclopenta[b]benzofurans
This work was supported by the Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche and the Centre National de la Recherche Scientifique.
Publication History
Received: 08 January 2018
Accepted after revision: 15 January 2018
Publication Date:
05 February 2018 (online)
Dedicated to Professor Miguel Yus on the occasion of his 70th 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.
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Key words
dearomatization - palladium(0) catalysis - (3+2) cycloaddition - nitrobenzofurans - vinylcyclopropanes - cyclopenta[b]benzofuransDearomatization reactions represent powerful methods for building high molecular complexity and diversity starting from readily available feedstock materials such as arenes and heteroarenes.[1] [2] [3] [4] For this reason, much effort has been devoted to their development, notably by means of robust metal-based catalytic processes.[2] In this particular area of research, palladium catalysis has undeniably shown great potential.[3,4] Interestingly though, the vast majority of such catalytic transformations have so far capitalized on the nucleophilic character of electron-rich aromatic rings (phenols, anilines, indoles, etc.),[3] and the complementary palladium-catalyzed dearomatization of electron-deficient systems remains comparatively scarce.[4] In 2014, Trost et al. reached a significant milestone in this field by demonstrating that several nitroarenes, including 5-nitroquinoline, could undergo a formal (3+2) dearomative cycloaddition with a trimethylenemethane equivalent (Scheme [1, a]).[4a] [5] More recently, we and the group of Hyland demonstrated that such an approach was not limited to the use of trimethylenemethane equivalents and that, under palladium(0) catalysis, vinylcyclopropanes (VCPs) (Scheme [1, b])[4b] [6] and vinylaziridines (Scheme [1, c])[4c] were also 1,3-dipole precursors capable of promoting the dearomatization of N-protected 3-nitroindoles.
As a continuation of our interest in the use of VCPs in palladium-catalyzed dearomatization reactions, we questioned if such a cycloaddition strategy could be applied to nitrobenzofurans. If successful, we anticipated that it would enable an efficient and atom-economical access to the cyclopenta[b]benzofuran core, a key scaffold prevalent in several bioactive flavaglines, such as (–)-rocaglamide (Scheme [1, d]).[7] [8] Although several synthetic methods to this structural motif have been developed,[8,9] such a straightforward palladium-catalyzed dearomative (3+2) cycloaddition approach is, to the best of our knowledge, unprecedented.[10]
At the outset of this study, the feasibility of a palladium catalyzed dearomative cycloaddition process between nitrobenzofurans and VCPs was surveyed in a model reaction between 5-bromo-2-nitrobenzofuran (1a)[11] and dicyano vinylcyclopropane 2a. When using a catalytic system composed of Pd2(dba)3·CHCl3 (2.5 mol%) and 1,2-bis(diphenylphosphino)ethane (dppe) (5 mol%) in toluene at room temperature, we were pleased to observe the formation of the desired diastereoisomeric cyclopenta[b]benzofuran 3aa in 1:1.2 dr (Scheme [2]).
Although the proof of concept had been rapidly achieved, despite full consumption of 2a, we were not able to reach full conversion of 1a as a probable result of the known propensity of VCPs to undergo competitive oligomerization in the presence of a palladium(0) complex.[12] In this context, we decided to optimize the reaction conditions to improve the efficiency of this new dearomative process (Table [1]).
Employing the Pd2(dba)3·CHCl3/dppe catalytic system and fixing the reaction time at 2 hours, the influence of the solvent was examined at room temperature. Switching from toluene to THF or dioxane did not lead to any significant improvement (Table [1], entries 2 and 3). In acetonitrile, full conversion of 1a was obtained but the cyclopenta[b]benzofuran 3aa (1:1 dr) was isolated in 68% yield (entry 4). Indeed, in this case, the concurrent formation of several by-products could be witnessed in the 1H NMR spectrum of the crude reaction mixture. Probing the use of chlorinated solvents (entries 5–7), excellent conversions were achieved in 1,2-dichloroethane and dichloromethane. In the latter case, the cyclopentannelation product 3aa (1:1 dr) was obtained in 88% yield and, as such, dichloromethane was selected for the rest of our study (entry 7). Next, we decided to evaluate whether other phosphorus-based ligands could improve the diastereoselectivity of this cycloaddition reaction. Analogs of dppe such as 1,3-bis(diphenylphosphino)propane (dppp) and bis(diphenylphosphino)methane (dppm) induced a significant decrease of reactivity without improving the stereoselectivity (entries 8 and 9). In the same way, bidentate 1,1′-bis(diphenylphosphino)ferrocene (dppf) and Xantphos, or monodentate triphenyl- and tri-(ortho-tolyl)phosphine led to poor results (entries 10–13). For this reason, dppe was identified as the optimum ligand for this transformation.
a Determined by 1H NMR analysis of the crude reaction mixture using 2-bromo-1,3,5-trimethoxybenzene as an internal standard.
b Yield of isolated product in parentheses.
c Determined by 1H NMR analysis of the crude reaction mixture.
d DCE = 1,2-dichloroethane.
With this optimized catalytic system in hand, we then studied the scope and limitations of this new dearomatization reaction. Employing vinylcyclopropane 2a, the influence of the 2-nitrobenzofuran partner was first surveyed (Scheme [3]).
Using 2-nitrobenzofuran (1b), the corresponding dearomatized cycloadduct 3ba was obtained in 90% yield and 1:1 dr. The reactivity of various 5-substituted 2-nitrobenzofurans was then evaluated. While, in all cases, no significant increase in the diastereoselectivity was observed, the stereoelectronic properties of the substituent present at position 5 did not seem to have a key impact on the overall efficiency of the dearomative cycloaddition process. Accordingly, cycloadducts bearing methyl (3ca), tert-butyl (3da), fluoro (3ea), chloro (3fa), methoxy (3ga) or trifluoromethoxy (3ha) groups were all obtained in satisfactory yields (68–88%). This trend was confirmed when subjecting the 6- and 7-substituted 2-nitrobenzofurans 1i–l to the reaction conditions. Indeed, the corresponding methyl-, bromo- and methoxy-substituted cyclopenta[b]benzofurans 3ia–la were isolated in yields ranging from 59–83% and approximately 1:1 dr values. On the other hand, 2-nitrobenzofurans 1m,n bearing a substituent at position 4 proved to be more sluggish in their reactions with 2a. The corresponding cycloadducts 3ma and 3na were both obtained in only 51% yield, suggesting that an increase of steric hindrance next to the electrophilic 3-position may, to some extent, impede the desired cycloaddition process. Whereas the diastereoselectivity was not significantly improved for 3ma (1:1.3 dr), the naphthyl-derived cyclopenta[b]benzofuran 3na was formed in a higher 1:2.3 dr.
Next, the influence of the vinylcyclopropane partner was evaluated by submitting 5-bromo-2-nitrobenzofuran (1a) to Pd(0)-catalyzed reactions with VCPs 2b–f (Scheme [4]).
Pleasingly, this novel palladium-catalyzed dearomatization reaction proved to be compatible with the use of VCP diesters 2b–d. Accordingly, the corresponding cyclopenta[b]benzofurans 3ab–ad were obtained in good to excellent yields (87–97%) and slightly better diastereoselectivities than in the previous series. Switching to the indan-1,3-dione-derived vinylcyclopropane 2e resulted in a significant improvement of the cycloaddition stereoselectivity (1:4.3 dr), albeit with a low 33% yield under the standard reaction conditions. When employing 2 equivalents of 5-bromo-2-nitrobenzofuran (1a) and a prolonged reaction time of 72 hours, the dearomative cycloaddition process could compete more efficiently with the polymerization of 2e, such that the desired cyclopentannulated product 3ae was obtained in a superior 81% yield (1:4.4 dr).[13] On the other hand, the use of Meldrum’s acid or barbituric acid derived VCPs 2f and 2g did not result in the desired dearomatization reaction. Whereas in the first case no reaction occurred, the degradation of 2g was preferentially observed over the formation of the desired cycloadduct 3ag.
Finally, we decided to test if this palladium-catalyzed dearomative cycloaddition reaction would be compatible with the use of isomeric 3-nitrobenzofurans. For this purpose, the 5-acetoxy derivative 4 was prepared and reacted with VCP 2a.[14] Satisfyingly, we obtained the desired cycloaddition product 5 in 94% yield (1.6:1 dr), suggesting that this new dearomatization method is not limited to 2-nitrobenzofurans (Scheme [5]).
In summary, we have herein demonstrated that a variety of 2-nitrobenzofurans undergo a palladium-catalyzed dearomative (3+2) cycloaddition with vinylcyclopropanes. This novel methodology offers an efficient and atom-economical access to a wide range of cyclopenta[b]benzofuran derivatives with average to excellent yields and can also be applied to the use of a 3-nitrobenzofuran.[15] Further studies concerning the development of an enantioselective variant of this dearomatization reaction are currently underway and will be reported in due course.
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Acknowledgment
We warmly thank Sandra Segondy for her contribution to the synthesis of several 2-nitrobenzofurans.
Supporting Information
- Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/s-0036-1591540.
- Supporting Information
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References and Notes
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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]+•.
For reviews, see:
For reviews, see:
For representative examples, see:
For seminal works on the dearomatization of nitroarenes, see:
For recent reviews on the reactivity of vinylcyclopropanes, see:
For recent reviews on the preparation and biological activities of cyclopenta[b]benzofuran-containing compounds, see:
For selected examples, see:
For alternative dearomatization of benzofurans leading to cyclopenta[b]benzofurans, see:
-
References and Notes
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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]+•.
For reviews, see:
For reviews, see:
For representative examples, see:
For seminal works on the dearomatization of nitroarenes, see:
For recent reviews on the reactivity of vinylcyclopropanes, see:
For recent reviews on the preparation and biological activities of cyclopenta[b]benzofuran-containing compounds, see:
For selected examples, see:
For alternative dearomatization of benzofurans leading to cyclopenta[b]benzofurans, see:
