Synthesis 2021; 53(22): 4272-4278
DOI: 10.1055/a-1538-8429
special topic
Special Issue dedicated to Prof. Sarah Reisman, recipient of the 2019 Dr. Margaret Faul Women in Chemistry Award

A de novo Synthesis of Oxindoles from Cyclohexanone-Derived γ-Keto-Ester Acceptors Using a Desaturative Amination–Cyclization Approach

Henry P. Caldora
a   Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
,
Sebastian Govaerts
a   Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
,
Shashikant U. Dighe
a   Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
,
Oliver J. Turner
b   Oncology R&D, Research & Early Development, AstraZeneca, Darwin building, 310, Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK
,
a   Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
› Author Affiliations
D.L. thanks the Engineering and Physical Sciences Research Council (EPSRC) for a Fellowship (EP/P004997/1) and the European Research Council for a research grant (No. 758427). H.C. thanks AstraZeneca for a Ph.D. Studentship.


Dedicated to Prof Sarah Reisman in recognition on her award of the inaugural Margaret Faul Women in Chemistry Award.

Abstract

Here we report a desaturative approach for oxindole synthesis. This method uses simple ethyl 2-(2-oxocyclohexyl)acetates and primary amine building blocks as coupling partners. A dual photoredox–cobalt manifold is used to generate a secondary aniline that, upon heating, cyclizes with the pendent ester functionality. The process operates under mild conditions and was applied to the modification of several amino acids, the blockbuster drug mexiletine, as well as the formation of dihydroquinolinones.

Supporting Information



Publication History

Received: 07 June 2021

Accepted after revision: 28 June 2021

Publication Date:
28 June 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

    • 1a Pennington LD, Moustakas DT. J. Med. Chem. 2017; 60: 3552
    • 1b Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
    • 1c Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845
    • 1d Lamberth C. Pest Manage. Sci. 2013; 69: 1106
    • 2a Marti C, Carreira EM. Eur. J. Org. Chem. 2003; 2003: 2209
    • 2b Leoni A, Locatelli A, Morigi R, Rambaldi M. Expert Opin. Ther. Pat. 2016; 26: 149
    • 3a Durbin MJ, Willis MC. Org. Lett. 2008; 10: 1413
    • 3b Jensen T, Madsen R. J. Org. Chem. 2009; 74: 3990
    • 3c Chen W.-T, Wei W.-T. Asian J. Org. Chem. 2018; 7: 1429
    • 3d Reddy CR, Jithender E, Krishna G, Reddy GV, Jagadeesh B. Org. Biomol. Chem. 2011; 9: 3940
    • 4a Singh R, Nagesh K, Yugandhar D, Prasanthi AV. G. Org. Lett. 2018; 20: 4848
    • 4b Marchese AD, Larin EM, Mirabi B, Lautens M. Acc. Chem. Res. 2020; 53: 1605
    • 5a Hennessy EJ, Buchwald SL. J. Am. Chem. Soc. 2003; 125: 12084
    • 5b Li Y, Wang K, Ping Y, Wang Y, Kong W. Org. Lett. 2018; 20: 921
    • 5c Liu C, Liu D, Zhang W, Zhou L, Lei A. Org. Lett. 2013; 15: 6166
    • 5d Yamamoto K, Qureshi Z, Tsoung J, Pisella G, Lautens M. Org. Lett. 2016; 18: 4954
    • 6a Wu Z.-J, Xu H.-C. Angew. Chem. Int. Ed. 2017; 56: 4734
    • 6b Ju X, Liang Y, Jia P, Li W, Yu W. Org. Biomol. Chem. 2012; 10: 498
    • 6c 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
    • 6d Meng Y, Guo L.-N, Wang H, Duan X.-H. Chem. Commun. 2013; 49: 7540
    • 6e Wang J.-Y, Zhang X, Bao Y, Xu Y.-M, Cheng X.-F, Wang X.-S. Org. Biomol. Chem. 2014; 12: 5582
  • 7 Nykaza TV, Li G, Yang J, Luzung MR, Radosevich AT. Angew. Chem. Int. Ed. 2020; 59: 4505
    • 8a Shelar SV, Argade NP. Org. Biomol. Chem. 2019; 17: 6671
    • 8b Lv J, Zhang-Negrerie D, Deng J, Du Y, Zhao K. J. Org. Chem. 2014; 79: 1111
    • 8c Jiang X, Zheng C, Lei L, Lin K, Yu C. Eur. J. Org. Chem. 2018; 2018: 1437
    • 8d Hartmann M, Streb C. J. Porous Mater. 2006; 13: 347
    • 8e van Deurzen MP. J, van Rantwijk F, Sheldon RA. J. Mol. Catal. B: Enzym. 1996; 2: 33
    • 8f Takeuchi Y, Tarui T, Shibata N. Org. Lett. 2000; 2: 639
    • 8g Jiang X, Yang J, Zhang F, Yu P, Yi P, Sun Y, Wang Y. Org. Lett. 2016; 18: 3154
  • 9 Dighe SU, Juliá F, Luridiana A, Douglas JJ, Leonori D. Nature 2020; 584: 75
    • 10a Koizumi Y, Jin X, Yatabe T, Miyazaki R, Hasegawa J.-Y, Nozaki K, Mizuno N, Yamaguchi K. Angew. Chem. Int. Ed. 2019; 58: 10893
    • 10b Shimomoto Y, Matsubara R, Hayashi M. Adv. Synth. Catal. 2018; 360: 3297
    • 10c Girard SA, Hu X, Knauber T, Zhou F, Simon M.-O, Deng G.-J, Li C.-J. Org. Lett. 2012; 14: 5606
    • 10d Hajra A, Wei Y, Yoshikai N. Org. Lett. 2012; 14: 5488
    • 10e Ichitsuka T, Komatsuzaki S, Masuda K, Koumura N, Sato K, Kobayashi S. Chem. Eur. J. 2021; in press; DOI: DOI: 10.1002/chem.202101439.
    • 10f Girard SA, Huang H, Zhou F, Deng G.-J, Li C.-J. Org. Chem. Front. 2015; 2: 279
  • 11 Maeda K, Matsubara R, Hayashi M. Org. Lett. 2021; 23: 1530
  • 12 Nicholas AM. d. P, Arnold DR. Can. J. Chem. 1982; 60: 2165
  • 13 Pirnot MT, Rankic DA, Martin DB. C, MacMillan DW. C. Science 2013; 339: 1593
    • 14a Gridnev AA, Ittel SD. Chem. Rev. 2001; 101: 3611
    • 14b Dempsey JL, Brunschwig BS, Winkler JR, Gray HB. Acc. Chem. Res. 2009; 42: 1995
  • 15 Manolis AS, Deering TF, Cameron J, Markestes NA. III. Clin. Cardiol. 1990; 13: 349
    • 16a Yang BH, Buchwald SL. Org. Lett. 1999; 1: 35
    • 16b Tian X, Li X, Duan S, Du Y, Liu T, Fang Y, Chen W, Zhang H, Li M, Yang X. Adv. Synth. Catal. 2021; 363: 1050
    • 16c Kuang Z, Li B, Song Q. Chem. Commun. 2018; 54: 34
    • 16d Zhang L, Qureshi Z, Sonaglia L, Lautens M. Angew. Chem. Int. Ed. 2014; 53: 13850
  • 17 See SI for more information.
  • 18 Liu L, Song L, Guo Y, Min D, Shi T, Zhang W. Tetrahedron 2018; 74: 354
  • 19 Poondra RR, Turner NJ. Org. Lett. 2005; 7: 863
  • 20 Sumiyoshi T, Enomoto T, Takai K, Takahashi Y, Konishi Y, Uruno Y, Tojo K, Suwa A, Matsuda H, Nakako T, Sakai M, Kitamura A, Uematsu Y, Kiyoshi A. ACS Med. Chem. Lett. 2013; 4: 244