Iron-Catalyzed Radical Methylation of Activated Alkenes with tert-Butanol as the Methyl Source

^◊ These authors contributed equally to this work.

Abstract

A free-radical-initiated methylation/addition/cyclization of N-arylacrylamides and a methylation/addition/elimination of quinines have been developed in which t-BuOH is used as a methyl source. These reactions provide effective and selective methods for the synthesis of various methylated oxindoles and quinones in moderate to good yields.

Key words

methylation - oxinidoles - quinones - arylacrylamides - quinones - cascade reaction

• References and Notes

• 1a Umezawa Y, Nishio O. Nucleic Acids Res. 2002; 30: 2183
• 1b Barreiro EJ, Kümmerle AE, Fraga CA. M. Chem. Rev. 2011; 111: 5215
• 2a Schönherr H, Cernak T. Angew. Chem. Int. Ed. 2013; 52: 12256
• 2b Bahl A, Barton P, Bowers K, Caffrey MV, Denton R, Gilmour P, Hawley S, Linannen T, Luckhurst CA, Mochel T, Perry MW. D, Riley RJ, Roe E, Springthorpe B, Stein L, Webborn P. Bioorg. Med. Chem. Lett. 2012; 22: 6694
• 2c Zhang L, Brodney MA, Candler J, Doran AC, Duplantier AJ, Efremov IV, Evrard E, Kraus K, Ganong AH, Haas JA, Hanks AN, Jenza K, Lazzaro JT, Maklad N, McCarthy SA, Qian W, Rogers BN, Rottas MD, Schmidt CJ, Siuciak JA, Tingley FD. III, Zhang AQ. J. Med. Chem. 2011; 54: 1724
• 2d Wood MR, Hopkins CR, Brogan JT, Conn PJ, Lindsley CW. Biochemistry 2011; 50: 2403
• 3a Chen Q, Ilies L, Yoshikai N, Nakamura E. Org. Lett. 2011; 13: 3232
• 3b Neufeldt SR, Seigerman CK, Sanford MS. Org. Lett. 2013; 15: 2302
• 3c Chen X, Li J.-J, Hao X.-S, Goodhue CE, Yu J.-Q. J. Am. Chem. Soc. 2006; 128: 78
• 4a Giri R, Maugel N, Li J.-J, Wang D, Breazzano SP, Saunders LB, Yu J.-Q. J. Am. Chem. Soc. 2007; 129: 3510
• 4b Romero-Revilla JA, García-Rubia A, Arrayas RG, Fernández-Ibáñez M. Á, Carretero JC. J. Org. Chem. 2011; 76: 9525
• 4c Dai H.-X, Stepan AF, Plummer MS, Zhang Y.-H, Yu J.-Q. J. Am. Chem. Soc. 2011; 133: 7222
• 4d Chen X, Goodhue CE, Yu J.-Q. J. Am. Chem. Soc. 2006; 128: 12634
• 5a Barsky L, Gschwend HW, McKenna J, Rodriguez HR. J. J. Org. Chem. 1976; 41: 3651
• 5b Tremont SJ, Ur Rahman H. J. Am. Chem. Soc. 1984; 106: 5759
• 5c Zhao Y, Chen G. Org. Lett. 2011; 13: 4850
• 5d Engle KM, Mei T.-S, Wasa M, Yu J.-Q. Acc. Chem. Res. 2012; 45: 788
• 6a Yao B, Song R.-J, Liu Y, Xie Y.-X, Li J.-H, Wang M.-K, Tang R.-Y, Zhang X.-G, Deng C.-L. Adv. Synth. Catal. 2012; 354: 1890
• 6b Li Z, Cui X, Niu L, Ren Y, Bian M, Yang X, Yang B, Yan Q, Zhao J. Adv. Synth. Catal. 2017; 359: 246
• 7a Minisci F, Bernardi R, Bertini F, Galli R, Perchinummo M. Tetrahedron 1971; 27: 3575
• 7b Ahn SK, Choi NS, Jeong BS, Kim KK, Journ DJ, Kim JK, Lee SJ, Kim JW, Il CH, Jew S.-S. J. Heterocycl. Chem. 2000; 37: 1141
• 7c Pan F, Lei Z.-Q, Wang H, Li H, Sun J, Shi Z.-J. Angew. Chem. Int. Ed. 2013; 52: 2063
• 8a Zhang Y, Feng J, Li C.-J. J. Am. Chem. Soc. 2008; 130: 2900
• 8b Zhu Y, Yan H, Lu L, Liu D, Rong G, Mao J. J. Org. Chem. 2013; 78: 9898
• 9 Wu T, Zhang H, Liu G. Tetrahedron 2012; 68: 5229

For selected reviews on oxindoles, see:
• 10a Jensen BS. CNS Drug Rev. 2002; 8: 353
• 10b Marti C, Carreira EM. Eur. J. Org. Chem. 2003; 2209
• 10c Galliford CV, Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 8748

For selected articles on quinones, see:
• 11a Morton RA. Biochemistry of Quinones . Academic Press; New York: 1965
• 11b Miyamura H, Shiramizu M, Matsubara R, Kobayashi S. Angew. Chem. Int. Ed. 2008; 47: 8093
• 11c Nowicka B, Kruk J. Biochim. Biophys. Acta 2010; 1797: 1587
• 11d Liu J.-K. Chem. Rev. 2006; 106: 2209
• 11e Shuai Z, Fei J, Dong B, Jing S. Chem. Commun. 2013; 49: 4558
• 11f Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257

For selected examples of the synthesis of oxindoles, see:
• 12a Klein JE. M. N, Perry A, Pugh DS, Taylor RJ. K. Org. Lett. 2010; 12: 3446
• 12b Wu T, Mu X, Liu G.-S. Angew. Chem. Int. Ed. 2011; 50: 12578
• 12c Wei W.-T, Zhou M.-B, Fan J.-H, Liu W, Song R.-J, Liu Y, Hu M, Xie P, Li J.-H. Angew. Chem. Int. Ed. 2013; 52: 3638
• 12d Li Y.-M, Sun M, Wang H.-L, Tian Q.-P, Yang S.-D. Angew. Chem. Int. Ed. 2013; 52: 3972
• 12e Zhou M.-B, Song R.-J, Ouyang X.-H, Liu Y, Wei W.-T, Deng G.-B, Li J.-H. Chem. Sci. 2013; 4: 2690
• 12f Li X, Xu X, Hu P, Xiao X, Zhou C. J. Org. Chem. 2013; 78: 7343
• 12g Matcha K, Narayan R, Antonchick AP. Angew. Chem. Int. Ed. 2013; 52: 7985
• 12h Meng Y, Guo L.-N, Wang H, Duan X.-H. Chem. Commun. 2013; 49: 7540
• 12i Wei X.-H, Li Y.-M, Zhou A.-X, Yang T.-T, Yang S.-D. Org. Lett. 2013; 15: 4158
• 12j Sakamoto R, Hirama N, Maruoka K. Org. Biomol. Chem. 2018; 16: 5412
• 12k Lu M, Liu Z, Zhang J, Tian Y, Qin H, Huang M, Hu S, Cai S. Org. Biomol. Chem. 2018; 16: 6564
• 12l Yoon H, Marchese AD, Lautens M. J. Am. Chem. Soc. 2018; 140: 10950
• 12m Lu K, Han X.-W, Yao W.-W, Luan Y.-X, Wang Y.-X, Chen H, Xu X.-T, Zhang K, Ye M. ACS Catal. 2018; 8: 3913

For selected examples of the synthesis of quinones, see:
• 13a Pirrung MC, Liu Y, Deng D, Halstead DK, Li Z, May JF, Wedel M, Austin DA, Webster NJ. G. J. Am. Chem. Soc. 2005; 127: 4609
• 13b Zhang H.-B, Liu L, Chen Y.-J, Wang D, Li C.-J. Adv. Synth. Catal. 2006; 348: 229
• 13c Gan X.-W, Jiang W, Wang W, Hu L.-H. Org. Lett. 2009; 11: 589
• 13d Fujiwara Y, Domingo V, Seiple IB, Gianatassio R, Del Bel M, Baran PS. J. Am. Chem. Soc. 2011; 133: 3292
• 13e Ilangovan A, Saravanakumar S, Malayappasamy S. Org. Lett. 2013; 15: 4968
• 13f Baral ER, Kim SH, Lee YR. Asian J. Org. Chem. 2016; 5: 1134
• 13g Gutiérrez-Bonet Á, Remeur C, Matsui JK, Molander GA. J. Am. Chem. Soc. 2017; 139: 12251
• 14 Xie J, Xu P, Li H, Xue Q, Jin H, Cheng Y, Zhu C.-J. Chem. Commun. 2013; 49: 5672
• 15 Xu Z, Yan C, Liu Z.-Q. Org. Lett. 2014; 16: 5670
• 16 Dai Q, Yu J, Jiang Y, Guo S, Yang H, Cheng J. Chem. Commun. 2014; 50: 3865
• 17 Fan J.-H, Zhou M.-B, Liu Y, Wei W.-T, Ouyang X.-H, Song R.-J, Li J.-H. Synlett 2014; 25: 657
• 18 Wang G, Wang S, Wang J, Chen S.-Y, Yu X.-Q. Tetrahedron 2014; 70: 3466
• 19a Coppa F, Fontana F, Minisci F, Barbosa MC. N, Vismara E. Tetrahedron 1991; 47: 7343
• 19b Commandeur C, Chalumeau C, Dessolin J, Laguerre M. Eur. J. Org. Chem. 2007; 3045
• 20 3-Ethyl-1,3-dimethyl-1,3-dihydro-2H-indol-2-one (1); Typical Procedure A mixture of N-methyl-N-phenylmethacrylamide (1 equiv, 0.2 mmol), Fe(acac)₃ (2 mol%, 0.004 mmol), PIFA (2 equiv, 0.4 mmol), and t-BuOH (2 mL) was refluxed at 120 °C for 9 h. When the reaction was complete, the mixture was concentrated under vacuum and the residue was purified by flash column chromatography (silica gel) to give a colorless liquid; yield: 78%. ¹H NMR (400 MHz, CDCl₃): δ = 7.26 (t, J = 7.6 Hz, 1 H), 7.16 (d, J = 7.2 Hz, 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 6.85 (d, J = 7.6 Hz, 1 H), 3.21 (s, 3 H), 1.97–1.88 (m, 1 H), 1.81–1.72 (m, 1 H), 1.34 (s, 3 H), 0.57 (t, J = 7.6 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 181.2, 143.2, 133.8, 127.6, 122.6, 122.4, 108.0, 49.1, 31.3, 26.1, 23.2, 8.7. MS (EI): m/z (%) = 189 (51.4), 160 (100.0). 2-Chloro-3-methylnaphthoquinone (19); Typical Procedure A mixture of 2-chloronaphthoquinone (1 equiv, 0.2 mmol), Fe(acac)₃ (2 mol%, 0.004 mmol), PIFA (2 equiv, 0.4 mmol), and t-BuOH (2 mL) was refluxed at 120 °C for 5 h. When the reaction was complete, the mixture was concentrated under vacuum and the residue was purified by flash column chromatography (silica gel) to give a yellow solid; yield: 71%. ¹H NMR (400 MHz, CDCl₃): δ = 8.13–8.07 (m, 2 H), 7.74–7.72 (m, 2 H), 2.32 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 182.5, 177.4, 144.8, 143.2, 134.1, 133.8, 131.5, 131.2, 127.1, 126.9, 14.4. MS (EI): m/z (%) = 208 (4.1), 206 (13.3), 171 (100.0).