Free Radical Cyclization of N-Arylacrylamides: Mild and Facile Synthesis of 3-Thiocyanato Oxindoles

Abstract

A novel and convenient oxidative radical cyclization of N-substituted N-arylacrylamides for the synthesis of 3-thiocyanated oxindoles has been developed by using AgSCN and K₂S₂O₈ as the radical source. This process allows a consistent and convenient access to SCN-containing heterocycles bearing a broad range of functional groups in good to excellent yields (up to 91%). Moreover, the use of inexpensive and readily available starting materials, operational simplicity, and excellent functional group tolerance makes this protocol practically attractive.

Key words

alkenes - oxindole - radical cyclization - silver - tandem reaction - thiocyanation

• References and Notes


For reviews, see:
• 1a Marti C. Carreira EM. Eur. J. Org. Chem. 2003; 2209
• 1b Lin H. Danishefsky SJ. Angew. Chem. Int. Ed. 2003; 42: 36
• 1c Galliford CV. Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 8748
• 1d Singh GS. Desta ZY. Chem. Rev. 2012; 112: 6104
• 1e Shen K. Liu X. Lin L. Feng X. Chem. Sci. 2012; 3: 327
• 1f Dalpozzo R. Bartoli G. Bencivenni G. Chem. Soc. Rev. 2012; 41: 7247
• 1g Ball-Jones NR. Badillo JJ. Franz AK. Org. Biomol. Chem. 2012; 10: 5165
• 1h Hong L. Wang R. Adv. Synth. Catal. 2013; 355: 1023
• 1i Song R.-J. Liu Y. Xie Y.-X. Li J.-H. Synthesis 2015; 47: 1195
• 1j Chen J.-R. Yu X.-Y. Xiao W.-J. Synthesis 2015; 47: 604

For reviews, see:
• 2a Klein JE. M. N. Taylor RJ. K. Eur. J. Org. Chem. 2011; 6821
• 2b Trost BM. Brennan MK. Synthesis 2009; 3003

For selected examples, see:
• 2c Wang J. Yuan Y. Xiong R. Zhang-Negrerie D. Du Y. Zhao K. Org. Lett. 2012; 14: 2210
• 2d Beyer A. Buendia J. Bolm C. Org. Lett. 2012; 14: 3948
• 2e Dey C. Kündig EP. Chem. Commun. 2012; 48: 3064
• 2f Jia Y.-X. Kündig EP. Angew. Chem. Int. Ed. 2009; 48: 1636
• 2g Piou T. Neuville L. Zhu J. Angew. Chem. Int. Ed. 2012; 51: 11561
• 3a Mu X. Wu T. Wang H.-Y. Guo Y.-L. Liu G.-S. J. Am. Chem. Soc. 2012; 134: 878
• 3b Jaegli S. Dufour J. Wei H.-L. Piou T. Duan X.-H. Vors J.-P. Neuville L. Zhu J. Org. Lett. 2010; 12: 4498
• 3c Wu T. Mu X. Liu G.-S. Angew. Chem. Int. Ed. 2011; 50: 12578
• 3d Wei H.-L. Piou T. Dufour J. Neuville L. Zhu J. Org. Lett. 2011; 13: 2244
• 3e Fabry DC. Stodulski M. Hoerner S. Gulder T. Chem. –Eur. J. 2012; 18: 10834
• 3f Liu L. Ishida N. Ashida S. Murakami M. Org. Lett. 2011; 13: 1666
• 3g Ueda S. Okada T. Nagasawa H. Chem. Commun. 2010; 46: 2462
• 3h Mekhaela MK. G. Bienza S. Lindena A. Heimgartner H. Helv. Chim. Acta 2004; 87: 2385
• 3i Anwar U. Fielding MR. Grigg R. Sridharan V. Urch CJ. J. Organomet. Chem. 2006; 691: 1476
• 4 Li Y.-M. Sun M. Wang H.-L. Tian Q.-P. Yang S.-D. Angew. Chem. Int. Ed. 2013; 52: 3972
• 5a Xie J. Xu P. Li H. Xue Q. Jin H. Cheng Y. Zhu C. Chem. Commun. 2013; 49: 5672
• 5b 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
• 5c Zhou S.-L. Guo L.-N. Wang H. Duan X.-H. Chem. –Eur. J. 2013; 19: 12970
• 5d Meng Y. Guo L.-N. Wang H. Duan X.-H. Chem. Commun. 2013; 49: 7540
• 5e Wang H. Guo L.-N. Duan X.-H. Chem. Commun. 2013; 49: 10370
• 6a 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
• 6b Wang H. Guo L.-N. Duan X.-H. Adv. Synth. Catal. 2013; 355: 2222
• 7a Matcha K. Narayan R. Antonchick AP. Angew. Chem. Int. Ed. 2013; 52: 7985
• 7b Wei X.-H. Li Y.-M. Zhou A.-X. Yang T.-T. Yang S.-D. Org. Lett. 2013; 15: 4158
• 7c Yuan Y. Shen T. Wang K. Jiao N. Chem. –Asian J. 2013; 8: 2932
• 8a Li X.-Q. Xu X.-S. Hu P. Xiao X.-Q. Zhou C. J. Org. Chem. 2013; 78: 7343
• 8b Yin F. Wang X.-S. Org. Lett. 2014; 16: 1128
• 9a Qiu J.-S. Wu D. Karmaker PG. Qi G. Chen P. Yin H. Chen F.-X. Org. Lett. 2017; 19: 4018
• 9b Wang Y.-F. Qiu J.-S. Gao Y. Lu F. Karmaker PG. Chen F.-X. Org. Biomol. Chem. 2015; 13: 365
• 9c Wu T. Mu X. Liu G. Angew. Chem. Int. Ed. 2011; 50: 12578
• 10a Guo L.-N. Wang H. Duan X.-H. Chem. Commun. 2013; 49: 7540
• 10b Fu W.-J. Xu F.-J. Fu Y.-Q. Zhu M. Xu C. Yu J.-Q. Zou D.-P. J. Org. Chem. 2013; 78: 12202
• 11a Mu X. Wu T. Wang H.-Y. Guo Y.-L. Liu G.-S. J. Am. Chem. Soc. 2012; 134: 878
• 11b Egami H. Shimizu R. Kawamura S. Sodeoka M. Angew. Chem. Int. Ed. 2013; 52: 4000
• 11c Xu P. Xie J. Xue Q.-C. Pan C.-D. Cheng Y.-X. Zhu CJ. Chem. –Eur. J. 2013; 19: 14039
• 11d Kong W. Casimiro M. Merino E. Nevado C. J. Am. Chem. Soc. 2013; 135: 14480
• 11e Kong W. Casimiro M. Fuentes N. Merino E. Nevado C. Angew. Chem. Int. Ed. 2013; 52: 13086
• 11f Wang Y.-F. Qiu J.-S. Kong D. Chen F.-X. Synlett 2014; 25: 1731
• 11g Fu W.-J. Xu F.-J. Fu Y.-Q. Xu C. Li S.-H. Zou D.-P. Eur. J. Org. Chem. 2014; 709
• 12a Li Y.-M. Wei X.-H. Li X.-A. Yang S.-D. Chem. Commun. 2013; 49: 11701
• 12b Shen T. Yuan YZ. Jiao N. Chem. Commun. 2014; 50: 554
• 13a Billard T. Langlois BR. Médebieele M. Tetrahedron Lett. 2001; 42: 3463
• 13b Grieco PA. Yokoyama Y. Williams E. J. Org. Chem. 1978; 43: 1283
• 13c Das B. Reddy VS. Krishnaiah M. Tetrahedron Lett. 2006; 47: 8471
• 14 Riemschneider R. Wojahn F. Orlick G. J. Am. Chem. Soc. 1951; 73: 5905
• 15 Billard T. Large S. Langlois BR. Tetrahedron Lett. 1997; 38: 65
• 16 Vorona S. Artamonova T. Zevatskii Y. Myznikov L. Synthesis 2014; 46: 781
• 17a De Mico A. Margarita R. Mariani A. Piancatelli G. Tetrahedron Lett. 1996; 37: 1889
• 17b Nair V. Nair LG. Tetrahedron Lett. 1998; 39: 4585
• 17c Nair V. George TG. Nair LG. Panicker SB. Tetrahedron Lett. 1999; 40: 1195
• 17d Wu G. Liu Q. Shen Y. Wu W. Wu L. Tetrahedron Lett. 2005; 46: 5831
• 17e Pan X. Lei M. Zou J.-P. Zhang W. Tetrahedron Lett. 2009; 50: 347
• 17f Fan W. Yang Q. Xu F. Li P. J. Org. Chem. 2014; 79: 10588
• 17g Castanheiro T. Suffert J. Donnard M. Gulea M. Chem. Soc. Rev. 2016; 45: 494
• 17h Chen Q. Lei Y.-J. Wang Y.-F. Wang C. Wang Y. Xu Z.-Q. Wang H. Wang R. Org. Chem. Front. 2017; 4: 369
• 17i Jiang G.-B. Zhu C. Li J.-X. Wu W.-Q. Jiang H.-F. Adv. Synth. Catal. 2017; 359: 1208
• 17j Ji F. Fan Y. Yang R. Yang Y. Yu D. Wang M. Li Z. Asian J. Org. Chem. 2017; 6: 682
• 17k For a direct electrophilic thiocyanation with cationic thiocyanato reagent, see: Wu D. Qiu J. Karmaker PG. Yin H. Chen F.-X. J. Org. Chem. 2018;
• 18 Yang H. Duan X.-H. Zhao J.-F. Guo L.-N. Org. Lett. 2015; 17: 1998
• 19a Mu X. Chen S. Zhen X. Liu G. Chem. –Eur. J. 2011; 17: 6039
• 19b Yasu Y. Koike T. Akita M. Org. Lett. 2013; 15: 2136
• 20a Zeng Y.-F. Tan D.-H. Chen Y. Lv W.-X. Liu X.-G. Li Q. Wang H. Org. Chem. Front. 2015; 2: 1511
• 20b Lia C.-C. Yang S.-D. Org. Biomol. Chem. 2016; 14: 4365
• 20c Mete TB. Khopade TM. Bhat RG. Tetrahedron Lett. 2017; 58: 415
• 20d Yang D.-S. Yan K. Wei W. Li G.-Q. Lu S. Zhao C. Tian L. Wang H. J. Org. Chem. 2015; 80: 11073
• 21a Tian Q.-S. Chen B. Zhang G.-Z. Green Chem. 2016; 18: 6236
• 21b Li J. Hao W.-J. Zhou P. Zhu Y.-L. Wang S.-L. Tua S.-J. Jiang B. RSC Adv. 2017; 7: 9693
• 21c Liu Y.-Y. Yang X.-H. Yang J. Songa R.-J. Li H-J. Chem. Commun. 2014; 50: 6906
• 21d Zhang H.-L. Gu Z.-X. Li Z.-Y. Pan C.-D. Li W.-P. Hu H.-W. Zhu C.-J. J. Org. Chem. 2016; 81: 2122
• 21e Qiu Y.-F. Zhu X.-Y. Li Y.-X. He Y.-T. Yang F. Wang J. Hua H.-L. Zheng L. Wang L.-C. Liu X.-Y. Liang Y.-M. Org. Lett. 2015; 17: 3694
• 22 1,3-Dimethyl-3-(thiocyanatomethyl)indolin-2-one (3a): A mixture of 1a (0.1 mmol), AgSCN (2, 0.15 mmol), K₂S₂O₈ (0.3 mmol) and Cs₂CO₃ (0.1 mmol) in CH₃CN (3.0 mL) was stirred under open air at 100 °C for 12 h. After completion of the reaction, the resulting mixture was diluted with EtOAc and H₂O and filtered through a pad of celite. Then the filtrate was extracted with EtOAc (3 ×). The combined organic layer was dried over anhyd Na₂SO₄ and concentrated under reduced pressure. The resulting crude product was purified by flash chromatography on silica gel with a mixture of petroleum ether and EtOAc as the eluent; colorless oil (21 mg, 91% yield). IR (neat): 2154, 1699, 1610, 1489, 1375, 1242, 1056, 1024, 912, 748, 694 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.39 (t, J = 8.0 Hz, 1 H), 7.29 (t, J = 7.2 Hz, 1 H), 7.16 (t, J = 7.6 Hz, 1 H), 6.93 (d, J = 7.6 Hz, 1 H), 3.43 (J_ab  = 16.8 Hz, 2 H), 3.25 (s, 3 H), 1.50 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 177.3, 143.3, 129.8, 129.3, 123.4, 123.1, 111.4, 108.6, 48.5, 40.7, 26.4, 22.6. HRMS: m/z [M + H]⁺ calcd for C₁₂H₁₃N₂OS: 233.0743; found: 233.0739.