Iron-Mediated Radical Nitrohalogenation Reactions of Enynes with tert-Butyl Nitrite

Abstract

A radical nitrohalogenation/cyclization of various enynes with tert-butyl nitrite has been developed that conveniently introduces useful nitro and halo groups into organic compounds. Some control experiments were performed to elucidate the mechanism. Further functional transformations proceeded well in this reaction system.

Key words

nitrohalogenation - cyclization - enynes - butyl nitrite - radical reaction - pyrrolidines

Publication History

Received: 20 February 2021

Accepted after revision: 28 May 2021

Accepted Manuscript online:
28 May 2021

Article published online:
15 June 2021

• References and Notes

• 1a Nitro Compounds: Recent Advances in Synthesis and Chemistry. Feuer H, Nielsen T. VCH; Weinheim: 1990
• 1b Ono N. The Nitro Group in Organic Synthesis . Wiley-VCH; Weinheim: 2001
• 1c Ballini R, Petrini M. ARKIVOC 2009; (ix): 195
• 2 Hata E, Yamada T, Mukaiyama T. Bull. Chem. Soc. Jpn. 1995; 68: 3629
• 3 Tanaka M, Muro E, Ando H, Xu Q, Fujiwara M, Souma Y, Yamaguchi Y. J. Org. Chem. 2000; 65: 2972
• 4 Siri O, Jaquinod L, Smith KM. Tetrahedron Lett. 2000; 41: 3583
• 5 Hwu JR, Chen K.-L, Ananthan S, Patel HV. Organometallics 1996; 15: 499
• 6 Maity S, Manna S, Rana S, Naveen T, Mallick A, Maiti D. J. Am. Chem. Soc. 2013; 135: 3355
• 7a Taniguchi T, Fujii T, Ishibashi H. J. Org. Chem. 2010; 75: 8126
• 7b Taniguchi T, Ishibashi H. Org. Lett. 2010; 12: 124
• 8 Grenier J.-L, Catteau J.-P, Cotelle P. Synth. Commun. 1999; 29: 1201
• 9 Stepanov AV, Veselovsky VV. Russ. Chem. Rev. 2003; 72: 327

For recent examples of radical nitration reactions with TBN, see:
• 10a Koley D, Colón OC, Savinov SN. Org. Lett. 2009; 11: 4172
• 10b Wu X.-F, Schranck J, Neumann H, Beller M. Chem. Commun. 2011; 47: 12462
• 10c Kilpatrick B, Heller M, Arns S. Chem. Commun. 2013; 49: 514
• 10d Shen T, Yuan Y, Jiao N. Chem. Commun. 2014; 50: 554
• 10e Majhi B, Kundu D, Ahammed S, Ranu BC. Chem. Eur. J. 2014; 20: 9862
• 10f Yan H, Rong G, Liu D, Zheng Y, Chen J, Mao J. Org. Lett. 2014; 16: 6306
• 10g Wei W, Zhu W, Wu Y, Huang Y, Liang H. Youji Huaxue 2017; 37: 1916
• 10h Liu Y, Zhang J.-L, Song R.-J, Qian P.-C, Li J.-H. Angew. Chem. Int. Ed. 2014; 53: 9017
• 10i Wei W.-T, Ying W.-W, Bao W.-H, Gao L.-H, Xu X.-D, Wang Y.-N, Meng X.-X, Chen G.-P, Li Q. ACS Sustainable Chem. Eng. 2018; 6: 15301
• 10j Dahiya A, Sahoo AK, Alam T, Patel B.-K. Chem. Asian J. 2019; 14: 4454

For selected reviews, see:
• 11a Yet L. Chem. Rev. 2000; 100: 2963
• 11b Aubert C, Buisine O, Malacria M. Chem. Rev. 2002; 102: 813
• 11c Zhang L, Sun J, Kozmin SA. Adv. Synth. Catal. 2006; 348: 2271
• 11d Aubert C, Fensterbank L, Gandon V, Malacria M. Top. Organomet. Chem. 2006; 19: 259
• 11e Jiménez-Núñez E, Echavarren AM. Chem. Rev. 2008; 108: 3326
• 11f Inglesby PA, Evans PA. Chem. Soc. Rev. 2010; 39: 2791
• 11g López F, Mascareñas JL. Beilstein J. Org. Chem. 2011; 7: 1075
• 11h Gilmore K, Alabugin IV. Chem. Rev. 2011; 111: 6513
• 12 Curran DP, Rakiewicz DM. J. Am. Chem. Soc. 1985; 107: 1448
• 13 Wang A.-F, Zhu Y.-L, Wang S.-L, Hao W.-J, Li G, Tu S.-J, Jiang B. J. Org. Chem. 2016; 81: 1099
• 14 Zou L, Wang L, Sun L, Xie X, Li P.-H. Chem. Commun. 2020; 56: 7933

For selected references, see:
• 15a Zhang L, Li Z, Liu Z.-Q. Org. Lett. 2014; 16: 3688
• 15b Wang Y.-Q, He Y.-T, Zhang L.-L, Wu X.-X, Liu X.-Y, Liang Y.-M. Org. Lett. 2015; 17: 4280
• 15c Wu W, Yi S, Yu Y, Huang W, Jiang H. J. Org. Chem. 2017; 82: 1224
• 15d An Y, Wu J. Org. Lett. 2017; 19: 6028
• 15e Ye K.-Y, Song Z, Sauer GS, Harenberg JH, Fu N, Lin S. Chem. Eur. J. 2018; 24: 12274
• 15f Li M, Wang C.-T, Qiu Y.-F, Zhu X.-Y, Han Y.-P, Xia Y, Li X.-S, Liang Y.-M. Chem. Commun. 2018; 54: 5334
• 15g Xuan J, Studer A. Chem. Soc. Rev. 2017; 46: 4329
• 15h Song S.-Z, Kang Q.-Q, Cao T.-T, Lei K.-W, Liu Y.-Y, Li Q, Wei W.-T. ChemistrySelect 2019; 4: 13380
• 15i Xu C.-H, Li Y, Li J.-H, Xiang J.-N, Deng W. Sci. China Chem. 2019; 62: 1463
• 15j Li Y, Pan G.-A, Luo M.-J, Li J.-H. Chem. Commun. 2020; 56: 6907
• 15k Qu Y, Xu W, Zhang J, Liu Y, Li Y, Song H, Wang Q. J. Org. Chem. 2020; 85: 5379
• 15l Mao K, Bian M, Dai L, Zhang J, Yu Q, Wang C, Rong L. Org. Lett. 2021; 23: 218
• 15m Qiu J.-K, Jiang B, Zhu Y.-L, Hao W.-J, Wang D.-C, Sun J, Wei P, Tu S.-J, Li G. J. Am. Chem. Soc. 2015; 137: 8928
• 15n Yu L.-Z, Wei Y, Shi M. Chem. Commun. 2017; 53: 8980
• 15o Ouyang X.-H, Song R.-J, Liu Y, Hu M, Li J.-H. Org. Lett. 2015; 17: 6038
• 15p Zhao Y, Hu Y, Wang H, Li X, Wan B. J. Org. Chem. 2016; 81: 4412
• 15q Li J, Zhang W.-W, Wei X.-J, Liu F, Hao W, Wang S, Li G, Tu S.-J, Jiang B. J. Org. Chem. 2017; 82: 6621
• 15r Xu X.-D, Cao T.-T, Meng Y.-N, Zhou G, Guo Z, Li Q, Wei W.-T. ACS Sustainable Chem. Eng. 2019; 7: 13491
• 15s Yu J.-X, Niu S, Hu M, Xiang J.-N, Li J.-H. Chem. Commun. 2019; 55: 6727
• 15t Liu H.-Y, Lu Y, Li Y, Li J.-H. Org. Lett. 2020; 22: 8819
• 16a Li Z.-J, Cui X, Niu L, Ren Y, Bian M, Yang X, Yang B, Yan Q, Zhao J. Adv. Synth. Catal. 2017; 359: 246
• 16b Zhang R, Yu H, Li Z, Yan Q, Li P, Wu J, Qi J, Jiang M, Sun L. Adv. Synth. Catal. 2018; 360: 1384
• 16c Ge Y, Tian Y, Wu J, Yan Q, Zheng L, Ren Y, Zhao J, Li Z. Chem. Commun. 2020; 56: 12656
• 16d Wu J, Zong Y, Zhao C, Yan Q, Sun L, Li Y, Zhao J, Ge Y, Li Z. Org. Biomol. Chem. 2019; 17: 794
• 17 CCDC 2056928 contains the supplementary crystallographic data for compound 1. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 18 (4Z)-4-[Iodo(phenyl)methylene]-3-methyl-3-(nitromethyl)-1-tosylpyrrolidine; Typical Procedure A mixture of the N-tosyl(2-methylprop-2-en-1-yl)(3-phenylprop-2-yn-1-yl)amine (1 equiv, 0.1 mmol), TBN (8 equiv, 0.8 mmol), KI (1 equiv, 0.1 mmol), FeSO₄·7H₂O (0.4 equiv, 0.04 mmol), and CH₃CN (1 mL) was kept in a sealed tube at 50 °C under N₂ for 6 h. When the reaction was finished, the mixture was concentrated under a vacuum and purified by flash column chromatography [silica gel, PE–EtOAc (10:1)] to give a white solid; yield: 46.3 mg (90%; Z/E = 9:1); mp 104–105 ℃. ¹H NMR (400 MHz, CDCl₃): δ = 7.76 (d, J = 8.0 Hz, 2 H), 7.41 (d, J = 8.0 Hz, 2 H), 7.36–7.31 (m, 3 H), 7.16–7.14 (m, 2 H), 4.18 (d, J = 12.4 Hz, 1 H), 4.03 (d, J = 15.6 Hz, 1 H), 4.00 (d, J = 12.4 Hz, 1 H), 3.90 (d, J = 15.1 Hz, 1 H), 3.61 (d, J = 9.8 Hz, 1 H), 3.23 (d, J = 9.7 Hz, 1 H), 2.48 (s, 3 H), 1.10 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 144.8, 144.3, 142.1, 131.7, 130.0, 129.1, 128.7, 128.1, 127.5, 95.1, 79.7, 61.2, 59.3, 47.0, 22.5, 21.6. HRMS (ESI): m/z for [M + H]⁺ calcd for C₂₀H₂₂IN₂O₄S; 513.0339; found: 513.0338.