Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2018; 29(14): 1842-1846
DOI: 10.1055/s-0037-1610189
DOI: 10.1055/s-0037-1610189
letter
Metal-free Deamidative Ugi Access to Isoindolinones
We thank the Ministry of Higher Education and Scientific Research (Algeria) and ENSTA ParisTech for financial support.Further Information
Publication History
Received: 16 April 2018
Accepted after revision: 24 May 2018
Publication Date:
10 July 2018 (online)
Abstract
A two-step isoindolone synthesis has been achieved by using an Ugi/oxidative vicarious nucleophilic substitution sequence starting from 3-nitrobenzoic acid and aromatic aldehydes. Loss of the amido group was observed as well as a further oxidative process towards hydroxyisoindolone derivatives after prolonged stirring open to the atmosphere.
Key words
Ugi reaction - 3-nitrobenzoic acid - intramolecular vicarious nucleophilic substitution - isolindolones - air oxidationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610189.
- Supporting Information
-
References and Notes
- 1a Dömling A. Chem. Rev. 2006; 106: 17
- 1b Multicomponent Reactions in Organic Synthesis. Zhu J. Wang Q. Wang M.-X. Wiley-VCH; Weinheim: 2014
- 1c Boyarskiy VP. Bokach NA. Luzyanin KV. Kukushkin VY. Chem. Rev. 2015; 115: 2698
- 1d Sharma UK. Sharma N. Vachhani DD. Van der Eycken EV. Chem. Soc. Rev. 2015; 44: 1836
- 1e Varadi A. Palmer TC. Dardashti RN. Majumdar S. Molecules 2016; 21: 19
- 1f Giustiniano M. Basso A. Mercalli V. Massarotti A. Novellino E. Tron GC. Zhu J. Chem. Soc. Rev 2017; 46: 1295
- 1g Lei J. Meng JP. Tang DY. Frett B. Chen ZZ. Xu ZG. Mol. Divers. 2018; 22: 503
- 2a Akritopoulou-Zanze I. Curr. Opin. Chem. Biol. 2008; 12: 324
- 2b Dömling A. Wang K. Wang W. Chem. Rev. 2012; 112: 3083
- 3a Speck K. Magauer T. Beilstein J. Org. Chem. 2013; 9: 2048
- 3b Di Mola A. Palombi L. Massa AT. Targets Heterocycl. Syst. 2014; 18: 113
- 3c Bhatia RK. Curr. Top. Med. Chem. 2017; 17: 189
- 4a Takahashi I. Kawakami T. Hirano E. Yokota H. Kitajima H. Synlett 1996; 353
- 4b Stuk TL. Assink BK. Bates RC. Erdman Jr TR. Fedij V. Jennings SM. Lassig JL. Smith RJ. Smith TL. Org. Process Res. Dev. 2003; 7: 851
- 5a Mertens A. Zilch JH. König B. Schäfer W. Poll T. Kampe W. Seidel H. Leser U. Leinert H. J. Med. Chem. 1993; 36: 2526
- 5b Pendrak I. Barney S. Wittrock R. Lambert DM. Kingsbury WD. J. Org. Chem. 1994; 59: 2623
- 6a Taylor EC. Zhou P. Jenning LD. Mao Z. Hu B. Jun J.-G. Tetrahedron Lett. 1997; 38: 521
- 6b Kumar S. Kumar N. Roy P. Sondhi SM. Mol. Divers. 2013; 17: 753
- 7a Hanusch-Kompa C. Ugi I. Tetrahedron Lett. 1998; 39: 2725
- 7b Zhang J. Jacobson A. Rusche JR. Herlihy W. J. Org. Chem. 1999; 64: 1074
- 7c Marcaccini S. Pepino R. Polo C. Pozo MC. Synthesis 2001; 85
- 7d Faggi C. Garcia-Valverde M. Marcaccini S. Menchi G. Org. Lett. 2010; 12: 788
- 7e Xu Z. Ayaz M. Cappelli AA. Hulme C. ACS Comb. Sci. 2012; 14: 460
- 7f Macsari I. Besidski Y. Csjernyik G. Nilsson LI. Sandberg L. Yngve U. Ahlin K. Bueters T. Eriksson AB. Lund P.-E. Venyike E. Oerther S. Blakeman KH. Luo L. Arvidsson PI. J. Med. Chem. 2012; 55: 6866
- 7g Trifilenkov AS. Ilyin AP. Kysil VM. Sandulenko YB. Ivachtchenko AV. Tetrahedron Lett. 2007; 48: 2563
- 7h Salcedo A. Neuville L. Zhu J. J. Org. Chem. 2008; 73: 3600
- 7i Zhang L. Zhao F. Zheng M. Zhai Y. Liu H. Chem. Commun. 2013; 49: 2894
- 7j Tyagi V. Khan S. Chauhan PM. S. Tetrahedron Lett. 2013; 54: 1279
- 7k Butani HH. Vachhani DD. Bhoya UC. Shah AK. Van der Eycken EV. Eur. J. Org. Chem. 2015; 2124
- 7l Ghandi M. Zarezadeh N. Abbasi A. Org. Biomol. Chem. 2015; 13: 8211
- 7m Garcia-Gonzalez MC. Hernandez-Vazquez E. Gordillo-Cruz RE. Miranda LD. Chem. Commun. 2015; 51: 11669
- 7n Huang J. Du X. Van Hecke K. Van der Eycken EV. Pereshivko OP. Peshkov VA. Eur. J. Org. Chem. 2017; 4379
- 7o El Kaim L. Grimaud L. Le Goff XF. Schiltz A. Org. Lett. 2011; 13: 534
- 8a Cristau P. Vors J.-P. Zhu J. QSAR Comb. Sci. 2006; 25: 519
- 8b Kalinski C. Umkehrer M. Gonnard S. Jäger N. Ross G. Hiller W. Tetrahedron Lett. 2006; 47: 2041
- 8c Luo J. Wu J. Dai W.-M. Diversity Oriented Synthesis 2014; 1: 29
- 8d Ghandi M. Zarezadeh N. Abbasi A. Mol. Div. 2016; 20: 483
- 9a Zidan A. Garrec J. Cordier M. El-Naggar AM. Abd El-Sattar NE. A. Ali AK. Hassan MA. El Kaïm L. Angew. Chem. Int. Ed. 2017; 56: 12179
- 9b Zidan A. Cordier M. El-Naggar AM. Abd El-Sattar NE. A. Hassan MA. Ali AK. El Kaïm L. Org. Lett. 2018; 20: 2568
- 10a Makosza M. Winiarski J. Acc. Chem. Res. 1987; 20: 282
- 10b Makosza M. Synthesis 1991; 103
- 10c Makosza M. Wojciechowski K. J. Liebigs Ann. Chem. 1997; 1805
- 10d Makosza M. Synthesis 2011; 2341
- 10e Makosza M. Wojciechowski K. Chem. Heterocycl. Compd. 2015; 51: 210
- 11a Makosza M. Surowiec M. Paszewski M. ARKIVOC 2004; ii: 172
- 11b Makosza M. Sypniewski M. Tetrahedron 1994; 50: 4913
- 11c Mąkosza M. Paszewski M. Synthesis 2002; 2203
- 11d Clayden J. Menet CJ. Tetrahedron Lett. 2003; 44: 3059
- 11e Mąkosza M. Kamieńska-Trela K. Paszewski M. Bechcicka M. Tetrahedron 2005; 61: 11952
- 12a Gundel W.-H. Bohnert S. Z. Naturforsch. 1985; 40b: 1409
- 12b Kobayashi K. Chikazawa Y. Tetrahedron 2016; 72: 5100
- 13 For a related oxydative cyclization of non-Ugi adducts towards isoindolinones, see: Shen J. You Q. Fu Q. Kuai C. Huang H. Zhao L. Zhuang Z. Org. Lett. 2017; 19: 5170
- 14 The crystallographic data for compound 3c can be obtained free of charge by using the reference CCDC 1835817 from the Cambridge Crystallographic Data Centre at www.ccdc.cam.ac.uk/ data_request_cif.
- 15 Typical Procedure for the Ugi/Oxidative VNS for 1a/2a To a solution of 4-chlorobenzaldehyde (281 mg, 2.0 mmol) in MeOH (2 mL) were added successively n-butylamine (0.19 mL, 2.0 mmol), 3-nitrobenzoic acid (334 mg, 2.0 mmol), and tert-butyl isocyanide (0.22 mL, 2.0 mmol). The resulting mixture was stirred at rt for 1 d. The solvent was removed under reduced pressure and the crude was purified by flash column chromatography on silica gel (EtOAc/n-pentane 30:70) to afford the Ugi adduct 1a as a white solid in 92 % yield (816 mg, 1.8 mmol). Mp 113–114 °C. Rf 0.4 (AcOEt/n-pentane 30:70). IR (thin film): 3424, 3315, 309, 2968, 2248, 1654, 1577, 1354, 1301. 1H NMR (400 MHz, CDCl3): δ = 8.32–8.26 (m, 2 H), 7.80 (dt, J = 7.6, 1.2 Hz, 1 H), 7.63 (td, J = 7.6, 0.9 Hz, 1 H), 7.48–7.37 (m, 4 H), 5.84 (br, 1 H), 5.66 (br, 1H), 3.31–3.19 (m, 2 H), 1.36 (s, 9 H), 1.35–1.22 (m, 2 H), 1.00–0.88 (m, 2 H), 0.58 (br, 3 H). 13C NMR (100.6 MHz, CDCl3): δ = 170.1, 168.0, 147.9, 138.1, 134.7, 133.8, 132.8, 130.7, 129.9, 129.2, 124.4, 121.7, 62.9, 51.8, 48.5, 31.7, 28.6, 19.8, 13.3. HRMS: m/z [M – CONHt-Bu] calcd for C18H18ClN2O3: 345.1006; found: 345.0999. To a solution of 1a (178 mg, 0.4 mmol) in DMSO (1 mL) was added potassium tert-butoxide (112 mg, 1 mmol, 2.5 equiv). The resulting mixture was stirred at rt for 1 h under an inert atmosphere. After completion of the reaction, HCl (1 mL, 18% solution in water) was added and the mixture diluted with ethyl acetate and washed with water. The organic layer was dried with MgSO4 and the solvent was removed under reduced pressure. The crude residue was purified by flash chromatography on silica gel (Et2O/n-pentane 60:40) to afford isoindolone 2a as a yellow oil in 60% yield (82 mg, 0.24 mmol). Rf 0.22 (Et2O/n-pentane 60:40). IR (thin film): 2964, 2933, 275, 2249, 1694, 1536, 1349. 1H NMR (400 MHz, CDCl3): δ = 8.71 (d, J = 2.1 Hz, 1 H), 8.34 (dd, J = 8.3, 2.1 Hz, 1 H), 7.37 (d, J = 8.6 Hz, 2 H), 7.32 (d, J = 8.3 Hz, 1 H), 7.08 (d, J = 8.6 Hz, 2 H), 5.53 (s, 1 H), 3.95 (dt, J = 14.1, 8.0 Hz, 1 H), 2.89–2.82 (m, 1 H), 1.57–1.48 (m, 2 H), 1.34–1.27 (m, 2 H), 0.89 (t, J = 7.3 Hz, 3 H). 13C NMR (100.6 MHz, CDCl3): δ = 166.3, 151.3, 148.8, 135.5, 134.0, 133.5, 129.90, 128.9, 126.9, 124.3, 119.5, 63.8, 40.4, 30.3, 20.2, 13.8. HRMS: m/z calcd for C18H17ClN2O3: 344.0928; found: 344.0926.
For some reviews on Ugi reactions, see:
For reviews on the chemistry and biological activities of isoindoles and isoindolones, see:
For some approaches using 2-formylbenzoic acid, see:
For some approaches using benzoic acids substituted by a leaving group at the ortho position, see:
For an Ugi/Diels–Alder access to isoindolinone, see:
For an Ugi–Smiles/Truce–Smiles access to isoindolinones, see:
For some other Ugi/SNAr strategies involving O and N nucleophiles, see:
For recent reports of C–C bond formation at this position from our group, see:
For reviews on VNS, see:
For other studies on oxidative VNS, see:
For a related oxidation of analogous isoindolinones to their hydroxyl derivatives, see: