Synthesis of Nitromethyl-Substituted Oxindole Derivatives via a Desulfonylation Cascade

Abstract

A cascade reaction giving nitromethyl-substituted oxindole derivatives was developed. The reaction used NaNO₂ as the nitro source and potassium peroxydisulfate as an oxidant. This reaction proceeded via a radical mechanism involving substitution–desulfonlylation–cyclization steps in one pot and afforded good yields under mild conditions without using toxic metal catalysts. The resultant nitromethyl-substituted oxindole derivatives are convenient and valuable structures for different derivative syntheses.

Key words

oxindole - desulfonylation - radical cyclization - potassium peroxydisulfate - sodium nitrite

• Reference and Notes

• 1a Li B.-J, Shi Z.-J. Chem. Soc. Rev. 2012; 41: 5588
• 1b Singh GS, Desta ZY. Chem. Rev. 2012; 112: 6104
• 1c Chen X, Engle KM, Wang D.-H, Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094
• 1d Zhang C, Tang C, Jiao N. Chem. Soc. Rev. 2012; 41: 3464
• 1e Wencel-Delord J, Dröge T, Liuand F, Glorius F. Chem. Soc. Rev. 2011; 40: 4740
• 1f Ashenhurst JA. Chem. Soc. Rev. 2010; 39: 540
• 1g Petrov KG, Stewart M, Melrose H, Hopkins B, McHarg A, Wallis R. Eur. J. Pharmacol. 1999; 375: 61
• 1h Petrov KG, Zhang Y, Carter M, Cockerill GS, Dickerson S, Gauthier CA, Guo Y, Mook RA, Rusnak DW, Walker AL, Wood ER, Lackey KE. Bioorg. Med. Chem. Lett. 2006; 16: 4686
• 1i Wu T, Zhang H, Liu G.-S. Tetrahedron 2012; 68: 5229
• 1j Jensen BS. CNS Drug Rev. 2002; 8: 353
• 1k Hong L, Wang R. Adv. Synth. Catal. 2013; 355: 1023
• 2a Beyer A, Buendia J, Bolm C. Org. Lett. 2012; 14: 3948
• 2b Ueda S, Okada T, Nagasawa H. Chem. Commun. 2010; 46: 2462
• 2c MacDonald JP, Badillo JJ, Arevalo GE, Silva-García A, Franz KA. ACS Comb. Sci. 2012; 14: 285
• 2d LaPorte MG, Tsegay S, Hong K, Lu C, Fang C, Wang L, Xie X, Floreancig PE. ACS Comb. Sci. 2013; 15: 344
• 2e Ball-Jons NR, Badillo JJ, Franz AK. Org. Biomol. Chem. 2012; 10: 5165
• 2f Wu T, Mu X, Liu G.-S. Angew. Chem. Int. Ed. 2011; 50: 12578
• 2g Meng Y, Guo L.-N, Wang H, Duan X.-H. Chem. Commun. 2013; 49: 7540
• 3a Pinto A, Neuville L, Retailleau P, Zhu JP. Org. Lett. 2006; 8: 4927
• 3b Miura T, Toyoshima T, Takahashi Y, Murakmi M. Org. Lett. 2009; 11: 2141
• 3c Zou LW, Bao XZ, Ma YY, Song YM, Qu JP, Wang BM. Chem. Commun. 2014; 50: 5760
• 3d Lv JL, Negrerie DZ, Deng J, Du YF, Zhao K. J. Org. Chem. 2014; 79: 1111
• 3e Zhou S, Guo L, Wang H, Duan X.-H. Chem. Eur. J. 2013; 19: 12970
• 3f Yin F, Wang X. Org. Lett. 2014; 16: 1128
• 3g Boominathan M, Nagataj M, Muthusubramahian S, Bhuvanesh N. RSC Adv. 2014; 4: 18549
• 3h Li ZJ, Zhang Y, Zhang LZ, Liu ZQ. Org. Lett. 2014; 16: 382
• 3i Shi LL, Wang YY, Yang HJ, Fu H. Org. Biomol. Chem. 2014; 12: 4372
• 3j Wang JY, Zhang X, Bao Y, Xu YM, Cheng XF, Wang XS. Org. Biomol. Chem. 2014; 12: 5582
• 4a O’Hagan D, Rzepa HS. Chem. Commun. 1997; 645
• 4b Hagmann WK. J. Med. Chem. 2008; 51: 4359
• 4c Li X, Xu X, Hu P, Xiao X, Zhou C. J. Org. Chem. 2013; 78: 7343
• 4d Deak G, Doda M, Gyorgy L, Hazai L, Sterk L. J. Med. Chem. 1977; 20: 1384
• 4e Hibino S, Choshi T. Nat. Prod. Rep. 2001; 18: 66
• 4f Trost BM, Xie J, Sieber JD. J. Am. Chem. Soc. 2011; 133: 20611
• 5a Kamano Y, Zhang HP, Ichihara Y, Kizu H, Komiyama K, Pettit GR. Tetrahedron Lett. 1995; 36: 2783
• 5b Volk B, Barkoczy J, Hegedus E, Udvari S, Gacsalyi I, Mezei T, Pallagi K, Kompagne H, Levay G, Egyed A, Harsing LG, Spedding M, Simig G. J. Med. Chem. 2008; 51: 2522
• 5c Christensen MK, Erichsen KD, Trojel-Hansen C, Tjornelund J, Nielsen SJ, Frydenvang K, Johansen TN, Nielsen B, Sehested M, Jensen PB, Lkaunieks M, Zaichenko A, Loza E, Kalvinsh L, Bjorkling F. J. Med. Chem. 2010; 53: 7140
• 5d Jiang T, Kuhen KL, Wolff K, Yin H, Bieza K, Caldwell J, Bursulaya B, Yao-Hsing WuT, He Y. Bioorg. Med. Chem. Lett. 2006; 16: 2105
• 6a Jia F, Liu K, Xi H, Lu S, Li Z. Tetrahedron Lett. 2014; 54: 6337
• 6b Li YM, Shen YH, Chang KJ, Yang SD. Tetrahedron Lett. 2014; 70: 1991
• 6c Wei WT, Zhou M, Fan J, Liu W, Song R, Liu Y, Hu M, Xie P, Li J. Angew. Chem. Int. Ed. 2013; 52: 3638
• 6d Li X, Xu X, Hu P, Xiao X, Zhou C. J. Org. Chem. 2013; 78: 7343
• 6e Tang S, Zhou D, Wang YC. Eur. J. Org. Chem. 2014; 17: 3656
• 6f Xu XS, Tang YC, Li XQ, Hong G, Fang MW, Du XH. J. Org. Chem. 2014; 79: 446
• 6g Liu JD, Zhuang SB, Gui QW, Chen X, Yang ZY, Tan Z. Eur. J. Org. Chem. 2014; 15: 3196
• 6h Gong W, Xu L, Ji T, Xie P, Qi X, Pittman CU. Jr, Zhou A. RSC Adv. 2014; 4: 6854
• 7a Kong W, Merino E, Nevado C. Angew. Chem. Int. Ed. 2014; 53: 5078
• 7b Kong W, Casimiro M, Fuentes N, Merino E, Nevado C. Angew. Chem. Int. Ed. 2013; 52: 13086
• 7c Kong W, Casimiro M, Merino E, Nevado C. J. Am. Chem. Soc. 2013; 135: 14480
• 7d Li L, Deng M, Zheng S, Xiong Y, Tan B, Liu X. Org. Lett. 2014; 16: 504
• 8a Suzuki H, Takeuchi T, Mori T. J. Org. Chem. 1997; 61: 5944
• 8b Taniguchi T, Fujii T, Ishibashi H. J. Org. Chem. 2010; 75: 8126
• 8c Ridd JH. Chem. Soc. Rev. 1991; 20: 149
• 8d Teuten EL, Loeppky RN. Org. Biomol. Chem. 2005; 3: 1097
• 9a Li YM, Wei XH, Li XA, Yang SD. Chem. Commun. 2013; 49: 11701
• 9b Wang H, Guo LN, Duan XH. Adv. Synth. Catal. 2013; 355: 2222
• 9c Mu X, Mu T, Wang H, Guo Y, Liu G. J. Am. Chem. Soc. 2012; 134: 878
• 9d Wei XH, Li YM, Zhou AX, Yang TT, Yang SD. Org. Lett. 2013; 15: 4151
• 10 General Procedure for the Synthesis of Nitromethyl-Substituted Oxindole Derivatives N-Methyl-N-(phenylsulfonyl)methacrylamide (2.0 mmol, 1.0 equiv) was added to a dried sealed tube, followed by the addition of NaHCO₃ (2 mmol, 1.0 equiv), NaNO₂ (4.0 mmol, 2 equiv), K₂S₂O₈ (2.0 equiv), and anhydrous MeCN (2 mL). The reaction mixture was stirred at 120 °C for 18 h. After the reaction was completed, the reaction mixture was cooled down to r.t. and diluted with EtOAc, then the combined organic layers were dried over Na₂SO₄, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (PE–EtOAc, 25:1) to provide the title compound 3a as a sticky solid in a 88% yield. The same procedure for producing other compounds 3b–j.1-Isopropyl-3-methyl-3-(nitromethyl)indolin-2-one (3a)Sticky solid. IR: 2925, 2854, 2359, 1714, 1611, 1556, 1452, 1357, 1213, 754 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.33–7.04 (arom. H, 4H), 4.96 (d, J=13.2 Hz, 1H), 4.77 (d, J=13.6 Hz, 1H), 4.68 (m, 1H), 1.56 (d, J=7.2 Hz, 6H), 1.40 (s, 3H) ppm. ¹³C NMR (100 Hz, CDCl₃): δ = 21.9, 29.4, 31.9, 44.3, 46.8, 79.1, 110.5, 122.6, 129.0, 129.5, 142.4, 177.0. ESI-MS: m/z calcd for C₁₃H₁₆N₂O₃: 249.1239 [M + H]⁺; found: 249.1249.