CF₃COOH/O₂-Mediated Metal-Free Domino Construction of the Isatin Skeleton

Abstract

Directed by the strategy of C–H activation, an efficient construction of the isatin skeleton was developed through aerobic oxidation of glycine esters. The reactions were performed under CF₃COOH/O₂ conditions in the absence of metal catalysts. The reaction mechanisms were investigated with control experiments.

Key words

metal-free - isatin skeleton - C–H activation - CF₃COOH - ­oxygen

• References

• 1 Singh GS, Desta ZY. Chem. Rev. 2012; 112: 6104
• 2a Tang BX, Song RJ, Wu CY, Liu Y, Zhou MB, Wei WT, Deng GB, Yin DL, Li JH. J. Am. Chem. Soc. 2010; 132: 8900
• 2b Rogness DC, Larock RC. J. Org. Chem. 2011; 76: 4980
• 2c Huang PC, Gandeepan P, Cheng CH. Chem. Commun. 2013; 49: 8540
• 2d Zi Y, Cai ZJ, Wang SY, Ji SJ. Org. Lett. 2014; 16: 3094
• 2e Ilangovan A, Satish G. J. Org. Chem. 2014; 79: 4984
• 3a Kuan SH. C, Sun W, Wang L, Xia C, Tay MG, Liu C. Adv. Synth. Catal. 2017; 359: 3484
• 3b Liu T, Yang H, Jiang Y, Fu H. Adv. Synth. Catal. 2013; 355: 1169
• 3c Garg P, Jadhav SD, Singh A. Asian J. Org. Chem. 2017; 6: 1019
• 3d See also ref. 2a.
• 4a Jia X, Zhu Y, Yuan Y, Zhang X, Lü S, Zhang L, Luo L. ACS Catal. 2016; 6: 6033
• 4b Ji H, Zhu Y, Shao Y, Liu J, Yuan Y, Jia X. J. Org. Chem. 2017; 82: 9859
• 5 Li W, Duan Z, Zhang X, Zhang H, Wang M, Jiang R, Zeng H, Liu C, Lei A. Angew. Chem. Int. Ed. 2015; 54: 1893
• 6 Liao YY, Gao YC, Zheng W, Tang RY. Adv. Synth. Catal. 2018; 360: 3391
• 7a Huo C, Wang C, Wu M, Jia X, Xie H, Yuan Y. Adv. Synth. Catal. 2014; 356: 411
• 7b Huo C, Yuan Y, Wu M, Jia X, Wang X, Chen F, Tang J. Angew. Chem. Int. Ed. 2014; 53: 13544
• 7c Jia X, Liu X, Shao Y, Yuan Y, Zhu Y, Hou W, Zhang X. Adv. Synth. Catal. 2017; 359: 4399
• 7d Li K, Tan G, Huang J, Song F, You J. Angew. Chem. Int. Ed. 2013; 52: 12942
• 7e Salman M, Zhu ZQ, Huang ZZ. Org. Lett. 2016; 18: 1526
• 7f Wei XH, Wang GW, Yang SD. Chem. Commun. 2015; 51: 832
• 7g Xie J, Huang ZZ. Angew. Chem. Int. Ed. 2010; 49: 10181
• 7h Xie Z, Liu X, Liu L. Org. Lett. 2016; 18: 2982
• 7i Zhang G, Zhang Y, Wang R. Angew. Chem. Int. Ed. 2011; 50: 10429
• 7j Zhang Y, Ni M, Feng B. Org. Biomol. Chem. 2016; 14: 1550
• 7k Zhu ZQ, Bai P, Huang ZZ. Org. Lett. 2014; 16: 4881
• 8a Huo C, Chen F, Yuan Y, Xie H, Wang Y. Org. Lett. 2015; 17: 5028
• 8b Huo C, Xie H, Wu M, Jia X, Wang X, Chen F, Tang J. Chem. Eur. J. 2015; 21: 5723
• 8c Huo C, Yuan Y, Chen F, Wang Y. Adv. Synth. Catal. 2015; 357: 3648
• 8d Jia X, Hou W, Shao Y, Yuan Y, Chen Q, Li P, Liu X, Ji H. Chem. Eur. J. 2017; 23: 12980
• 8e Jia X, Lu S, Yuan Y, Zhang X, Zhang L, Luo L. Org. Biomol. Chem. 2017; 15: 2931
• 8f Jia X, Peng F, Qing C, Huo C, Wang X. Org. Lett. 2012; 14: 4030
• 8g Liu J, Wang Y, Yu L, Huo C, Wang X, Jia X. Adv. Synth. Catal. 2014; 356: 3214
• 8h Lu S, Zhu Y, Ma X, Jia X. Adv. Synth. Catal. 2016; 358: 1004
• 8i Richter H, Mancheno OG. Org. Lett. 2011; 13: 6066
• 8j Xie Z, Jia J, Liu X, Liu L. Adv. Synth. Catal. 2016; 358: 919
• 8k Li H, Huang S, Wang Y, Huo C. Org. Lett. 2018; 20: 92
• 8l See also ref. 4a.
• 9 Intramolecular Cyclization; General Procedure A: A 25 mL round-bottom flask containing N-alkyl-N-arylglycinate (1 mmol), CF₃COOH (0.5 mmol), and MeCN (5 mL) was stirred at 70 °C under O₂ (1 atm) for 12 h. CF₃COOH (0.5 mmol) was added and, after stirring for 36 h, the reaction mixture was concentrated under reduced pressure and the crude product was purified by column chromatography on silica gel.5-Methoxy-1-methylindoline-2,3-dione (2i)Prepared by following General Procedure A using ethyl N-(4-methoxyphenyl)-N-methylglycinate (223 mg, 1.0 mmol). Purification by column chromatography (n-hexane/EtOAc, 5:2) gave 2i (120 mg, 63%) as a red solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.17–7.13 (m, 2 H), 6.82 (d, J = 8.4 Hz, 1 H), 3.81 (s, 3 H), 3.22 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 183.7, 158.3, 156.6, 145.3, 124.6, 117.8, 110.9, 109.6, 56.0, 26.2. HRMS (ESI⁺): m/z [M +  Na]⁺ calcd for C₁₀H₉NNaO₃: 214.0475; found: 214.0476.
• 10 Intermolecular Cyclization; General Procedure B: A 25 mL round-bottom flask with N-H-N-arylglycinate (1 mmol), CF₃COOH (0.5 mmol) and MeCN (5 mL) was stirred at 70 °C under O₂ (1 atm) for 6 h. CF₃COOH (0.5 mmol) was added and, after stirring for 6 h, the reaction mixture was concentrated under reduced pressure and the crude product was purified by column chromatography on silica gel.Methyl 2-(5-Isopropyl-2,3-dioxoindolin-1-yl)acetate (4b)Prepared by following General Procedure B using methyl (4-isopropylphenyl) glycinate (207 mg, 1.0 mmol). Purification by column chromatography (n-hexane/EtOAc, 8:1) gave 4b (98 mg, 75%) as a red solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.53 (s, 1 H), 7.46 (d, J = 8.1 Hz, 1 H), 6.74 (d, J = 8.1 Hz, 1 H), 4.49 (s, 2 H), 3.79 (s, 3 H), 2.90 (hept, J = 6.8 Hz, 1 H), 1.24 (d, J = 6.9 Hz, 6 H). ¹³C NMR (101 MHz, CDCl₃): δ = 182.8, 167.4, 158.3, 148.3, 145.3, 136.8, 123.4, 117.7, 110.0, 52.8, 41.1, 33.5, 23.8 (2C). MS (ESI⁺): m/z = 262.05 [M + H]⁺. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₁₄H₁₅NNaO₄: 284.0893; found: 284.0889.
• 11 Detailed analysis conditions for intermediates I: A 25 mL round-bottom flask containing 1a (1 mmol), CF₃COOH (0.5 mmol), TEMPO (1 equiv), and MeCN (5 mL) was stirred at 70 °C under O₂ (1 atm) for 12 h. The reaction mixture was concentrated under reduced pressure and the crude material was analyzed by HRMS-APCI using ESI⁺ ionization.Detailed analysis conditions for intermediates D, E, F, and H: To a 25 mL round-bottom flask containing 3g (1 mmol), CF₃COOH (0.5 mmol), and MeCN (5 mL) was stirred at 70 °C under O₂ (1 atm) for 2 h, then the reaction mixture was concentrated under reduced pressure and the crude material was analyzed by HRMS-APCI using ESI⁺ ionization.