Enantioselective N-Alkylation of Nitroindoles under Phase-Transfer Catalysis

Abstract

An asymmetric phase-transfer-catalyzed N-alkylation of substituted indoles with various Michael acceptors was studied. Acidities of nitroindoles were determined in acetonitrile by UV-Vis spectrophotometric titration. There was essentially no correlation between acidity and reactivity in the aza-Michael reaction. The position of the nitro group on the indole ring was essential to control the stereoselectivity of the reaction. Michael adducts were obtained in high yields and moderate enantioselectivities in the reaction between 4-nitroindole and various Michael acceptors in the presence of cinchona alkaloid based phase-transfer catalysts. In addition to outlining the scope and limitations of the method, the geometries of the transition states of the reaction were calculated.

Key words

asymmetric catalysis - heterocycles - Michael addition - organocatalysis­ - phase-transfer catalysis

• References

• 1 For a recent review, see: Ciulla MG, Kumar K. Tetrahedron Lett. 2018; 59: 3223
• 2 Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845

For reviews of pharmaceutically active indole derivatives, see:
• 3a Kochanowska-Karamyan AJ, Hamann MT. Chem. Rev. 2010; 110: 4489
• 3b Sravanthi TV, Manju SL. Eur. J. Pharm. Sci. 2016; 91: 1
• 3c Singh TP, Singh OM. Mini-Rev. Med. Chem. 2018; 18: 9

For reviews, see:
• 4a Bandini M, Eichholzer A. Angew. Chem. Int. Ed. 2009; 48: 9608
• 4b Dalpozzo R. Chem. Soc. Rev. 2015; 44: 742
• 4c Chen J.-B, Jia Y.-X. Org. Biomol. Chem. 2017; 15: 3550
• 5a Fan Y, Kass SR. J. Org. Chem. 2017; 82: 13288
• 5b Liu L, Ma H, Xiao Y, Du F, Qin Z, Li N, Fu B. Chem. Commun. 2012; 48: 9281
• 5c Wu K, Jiang Y.-J, Fan Y.-S, Sha D, Zhang S. Chem. Eur. J. 2013; 19: 474
• 6a Zhou Y, Li C, Yuan X, Zhang F, Liu X, Liu P. Org. Biomol. Chem. 2019; 17: 3343
• 6b Chaudhary B, Diwaker M, Sharma S. Org. Chem. Front. 2018; 5: 3133
• 6c Sandtorv AH. Adv. Synth. Catal. 2015; 357: 2403
• 7a Trost BM, Osipov M, Dong G. J. Am. Chem. Soc. 2010; 132: 15800
• 7b Sevov CS, Zhou JS, Hartwig JF. J. Am. Chem. Soc. 2014; 136: 3200
• 7c Trost BM, Gnanamani E, Hung C.-I. Angew. Chem. Int. Ed. 2017; 56: 10451
• 7d Ye Y, Kim S.-T, Jeong J, Baik M.-H, Buchwald SL. J. Am. Chem. Soc. 2019; 141: 3901
• 8a Zhang L, Wu B, Chen Z, Hu J, Zeng X, Zhong G. Chem. Commun. 2018; 54: 9230
• 8b Cai Y, Gu Q, You S.-L. Org. Biomol. Chem. 2018; 16: 6146
• 8c Chen M, Sun J. Angew. Chem. Int. Ed. 2017; 56: 4583
• 8d Cai Q, Zheng C, You S.-L. Angew. Chem. Int. Ed. 2010; 49: 8666
• 9a Bandini M, Eichholzer A, Tragni M, Umani-Ronchi A. Angew. Chem. Int. Ed. 2008; 47: 3238
• 9b Bandini M, Bottoni A, Eichholzer A, Miscione GP, Stenta M. Chem. Eur. J. 2010; 16: 12462
• 10 Hong L, Sun W, Liu C, Wang L, Wang R. Chem. Eur. J. 2010; 16: 440

For our previous articles on aza-Michael reactions, see:
• 11a Žari S, Kudrjashova M, Pehk T, Lopp M, Kanger T. Org. Lett. 2014; 16: 1740
• 11b Metsala A, Žari S, Kanger T. ChemCatChem 2016; 8: 2961
• 11c Žari S, Metsala A, Kudrjashova M, Kaabel S, Järving I, Kanger T. Synthesis 2015; 47: 875
• 11d Kriis K, Melnik T, Lips K, Juhanson I, Kaabel S, Järving I, Kanger T. Synthesis 2017; 49: 604
• 12 Yang J, Li T, Zhou H, Li N, Xie D, Li Z. Synlett 2017; 28: 1227
• 13 For PTC with hydrogen bond donors, see: Wang H. Catalysts 2019; 9
• 14 Gomez-Bengoa E, Linden A, López R, Múgica-Mendiola I, Oiarbide M, Palomo C. J. Am. Chem. Soc. 2008; 130: 7955
• 15 Kütt A, Leito I, Kaljurand I, Sooväli L, Vlasov VM, Yagupolskii LM, Koppel IA. J. Org. Chem. 2006; 71: 2829
• 16 Raamat E, Kaupmees K, Ovsjannikov G, Trummal A, Kütt A, Saame J, Koppel I, Kaljurand I, Lipping L, Rodima T, Pihl V, Koppel IA, Leito I. J. Phys. Org. Chem. 2013; 26: 162
• 17 Sasson Y, Bilman N. J. Chem. Soc., Perkin Trans. 2 1989; 2029
• 18 Denmark SE, Weintraub RC. Heterocycles 2011; 82: 1527
• 19 Nicolaou KC, Liu G, Beabout K, McCurry MD, Shamoo Y. J. Am. Chem. Soc. 2017; 139: 3736
• 20 Bernal P, Fernández R, Lassaletta JM. Chem. Eur. J. 2010; 16: 7714
• 21 Wang X, Lv J, Liu L, Wang Y, Wu Y. J. Mol. Catal. A: Chem. 2007; 276: 102
• 22 He Z, Yang X, Jiang W. Org. Lett. 2015; 17: 3880
• 23 Reitel K, Kriis K, Järving I, Kanger T. Chem. Heterocycl. Compd. 2018; 54: 929
• 24 Pelkey ET, Gribble GW. Tetrahedron Lett. 1997; 38: 5603
• 25 Cheng Q, Zhang F, Guo Y.-L, You S.-L. Angew. Chem. Int. Ed. 2018; 57: 2134
• 26a Therkelsen FD, Hansen A.-L, Pedersen EB, Nielsen C. Org. Biomol. Chem. 2003; 1: 2908
• 26b Chen S.-j, Lu P.-G, Cai C. RSC Adv. 2015; 5: 13208
• 27 Oare DA, Henderson MA, Sanner MA, Heathcock CH. J. Org. Chem. 1990; 55: 132
• 28 Manjolinho F, Grünberg MF, Rodríguez N, Gooßen LJ. Eur. J. Org. Chem. 2012; 4680
• 29 Khopade TM, Warghude PK, Mete TB, Bhat RG. Tetrahedron Lett. 2019; 60: 197
• 30 Liu D.-N, Tian S.-K. Chem. Eur. J. 2009; 15: 4538
• 31 Berti F, Bincoletto S, Donati I, Fontanive G, Fregonesea M, Benedetti F. Org. Biomol. Chem. 2011; 9: 1987
• 32 Al-Masum M, Liu K.-Y. Tetrahedron Lett. 2011; 52: 5090
• 33 Pan G.-F, Zhu X.-Q, Guo R.-L, Gao Y.-R, Wang Y.-Q. Adv. Synth. Catal. 2018; 360: 4774
• 34 Bentley SC, Davies SG, Lee JA, Roberts PM, Thomson JE. Org. Lett. 2011; 13: 2544