Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review

  • Debjit Basu
  • Sarvesh Kumar
  • Sai Sudhir V
  • Rakeshwar Bandichhor
Review Article

Abstract

C-H activation in the synthesis of medicinally relevant molecules is reviewed. C-H activation is one of the most powerful components in the C-C or C-heteroatom bond formation tool box. This represents such an alternative which has provided the greener solutions to the organometallic/synthetic organic chemistry aiming to the synthesis of complex molecules. In recent years, there has been explosive growth in this area. In this review article we have presented effective methods of C-H activation employed in the synthesis of medicinally relevant molecules since 2010.

Graphical Abstract:

C-H activation in the synthesis of medicinally relevant molecules is reviewed. C-H activation is one of the most powerful components in the C-C or C-heteroatom bond formation tool box. This represents such an alternative which has provided the greener solutions to the organometallic/synthetic organic chemistry aiming to the synthesis of complex molecules. In recent years, there is explosive growth in this area. In this review article we have presented effective methods of C-H activation employed in the synthesis of medicinally relevant molecules.

Keywords

C-H activation organometallic synthesis effective methods greener solution pharmaceutical targets 

Notes

Acknowledgements

We thank the management of Dr. Reddy’s Laboratories Ltd for supporting this work.

References

  1. 1.
    (a) Selected reviews on C-H activation: (a) Wencel-Delord J, Dröge T, Liu F and Glorius F 2011 Towards mild metal-catalyzed C–H bond activation Chem. Soc. Rev. 40 4740; (b) Yeung C S and Dong V M 2011 Catalytic Dehydrogenative Cross-Coupling: Forming Carbon-Carbon Bonds by Oxidizing Two Carbon-Hydrogen Bonds Chem. Rev. 111 1215; (c) Jia C, Kitamura T and Fujiwara Y 2001 Catalytic Functionalization of Arenes and Alkanes via C-H Bond Activation Acc. Chem. Res34 633; (d) Chen D Y-K and Youn S W 2012 C-H Activation: A Complementary Tool in the Total Synthesis of Complex Natural Products Chem. Eur. J18 9452; (e) Yamaguchi J, Yamaguchi A D and Itami K 2012 C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals Angew. Chem. Int. Edit51 8960Google Scholar
  2. 2.
    Wencel-Delord J and Glorius F 2013 C–H bond activation enables the rapid construction and late-stage diversification of functional molecules Nature Chem. 5 369CrossRefGoogle Scholar
  3. 3.
    (a) Li C-J and Trost B M 2008 Green chemistry for chemical synthesis Proc. Natl. Acad. Sci. USA 105 13197; (b) Anastas P T and Warner J C 1998 Green Chemistry: Theory and Practice (New York: Oxford University Press)Google Scholar
  4. 4.
    Gensch T, Hopkinson M N, Glorius F and Wencel-Delord J 2016 Mild metal-catalyzed C–H activation: examples and concepts Chem. Soc. Rev. 45 2900CrossRefGoogle Scholar
  5. 5.
    Balcells D, Clot E and Eisenstein O 2010 C-H Bond Activation in Transition Metal Species from a Computational Perspective Chem. Rev. 110 749CrossRefGoogle Scholar
  6. 6.
    (a) Li C J 2009 Cross-Dehydrogenative Coupling (CDC): Exploring C-C Bond Formations beyond Functional Group Transformations Acc. Chem. Res. 42 335; (b) Ashenhurst J A 2010 Intermolecular oxidative cross-coupling of arenes Chem. Soc. Rev39 540; (c) Bugaut X and Glorius F 2011 Palladium-catalyzed selective dehydrogenative cross-couplings of heteroarenes Angew. Chem. Int. Edit50 7479Google Scholar
  7. 7.
    (a) Jiang B, Smallheer J M, Amaral-Ly C and Wuonola M A 1994 Total Synthesis of (\(\pm )\)-Dragmacidin: A Cytotoxic Bis(indole)alkaloid of Marine Origin J. Org. Chem. 59 6823; (b) Kawasaki T, Ohno K, Enoki H, Umemoto Y and Sakamoto M 2002 Syntheses of bis (indolyl)-piperazine alkaloids, dragmacidin B and C, and dihydrohamacanthin A Tetrahedron Lett.  43 4245; (c) Kawasaki T, Enoki H, Matsumura K, Ohyama M, Inagawa M and Sakamoto M 2000 First Total Synthesis of Dragmacidin A via Indolylglycines Org. Lett2 3027; (d) Tonsiengsom F, Miyake F Y, Yakushijin K and Horne D A 2006 Reduction of 2,5-Bis (\(3^{\prime }\)-indolyl) pyrazines to 2,5-Bis (\(3^{\prime }\)-indolyl) piperazines: Synthesis of Bisindolylpiperazine Marine Alkaloids Dragmacidin A, B, and C Synthesis 49; (e) Miyake F Y, Yakushijin Kand Horne D A 2000 A Facile Synthesis of Dragmacidin B and 2,5-Bis (6\(^{\prime }\)-bromo-3\(^{\prime }\)-indolyl) piperazine Org. Lett. 2 3185Google Scholar
  8. 8.
    (a) Yang C G, Wang J, Tang X X and Jiang B 2002 Asymmetric aminohydroxylation of vinyl indoles: a short enantioselective synthesis of the bisindole alkaloids dihydrohamacanthin A and dragmacidin A Tetrahedron: Asymmetr. 13 383; (b) Jiang B and Gu X H 2000 Syntheses of Bis (3\(^{\prime }\)-indolyl)-2(1H)-pyrazinones Heterocycles 53 1559Google Scholar
  9. 9.
    (a) Garg N K and Stoltz B M 2006 A unified synthetic approach to the pyrazinone dragmacidins Chem. Commun. 3769; (b) Garg N K, Sarpong R and Stoltz B M 2002 The First Total Synthesis of Dragmacidin D J. Am. Chem. Soc124 13179; (c) Garg N K, Caspi D D and Stoltz B M 2006 The Utility of the Classical and Oxidative Heck Reactions in Natural Product Synthesis: Studies Directed toward the Total Synthesis of Dragmacidin F Synlett 3081Google Scholar
  10. 10.
    Garg N K, Caspi D D and Stoltz B M 2005 Development of an Enantiodivergent Strategy for the Total Synthesis of (+)- and (-)-Dragmacidin F from a Single Enantiomer of Quinic Acid J. Am. Chem. Soc127 5970CrossRefGoogle Scholar
  11. 11.
    Mandal D, Yamaguchi A D, Yamaguchi J and Itami K 2011 Synthesis of Dragmacidin D via Direct C-H Couplings J. Am. Chem. Soc133 19660CrossRefGoogle Scholar
  12. 12.
    Gutekunst W R and Baran P S 2011 Total Synthesis and Structural Revision of the Piperarborenines via Sequential Cyclobutane C–H Arylation J. Am. Chem. Soc133 19076CrossRefGoogle Scholar
  13. 13.
    Ramkumar N and Nagarajan R 2013 Total Synthesis of Calothrixin A and B via C–H Activation J. Org. Chem78 2802CrossRefGoogle Scholar
  14. 14.
    (a) Choshi T and Hibino S 2009 Progress towards the Total Synthesis of the Bioactive Calothrixins A and B Heterocycles 77 85; (b) Tohyama S, Choshi T, Matsumoto K, Yamabuki A, Hieda Y, Nobuhiro J and Hibino S 2010 Total Synthesis of Bioactive Indolo[3,2-j]phenanthridine Alkaloid, Calothrixin B Heterocycles 82 397Google Scholar
  15. 15.
    Choy A, Colbry N, Huber C, Pamment M and Duine J V 2008 Development of a Synthesis For a Long-Term Oxazolidinone Antibacterial Org. Process Res. Dev12 884CrossRefGoogle Scholar
  16. 16.
    Hennessy E J and Buchwald S L 2003 Synthesis of Substituted Oxindoles from \(\upalpha \)-Chloroacetanilides via Palladium-Catalyzed C-H Functionalization J. Am. Chem. Soc. 125 12084CrossRefGoogle Scholar
  17. 17.
    Kiser E J, Magano J, Shine R J and Chen M H 2012 Kilogram-Lab-Scale Oxindole Synthesis via Palladium-Catalyzed C–H Functionalization Org. Process Res. Dev16 255CrossRefGoogle Scholar
  18. 18.
    Jacobson R M and Raths R A 1979 Total synthesis of heptamethyl lithospermate J. Org. Chem. 44 4013CrossRefGoogle Scholar
  19. 19.
    Malley S J O, Tan K L, Watzke A, Bergman R G and Ellman J A 2005 Total Synthesis of (+)-Lithospermic Acid by Asymmetric Intramolecular Alkylation via Catalytic C-H Bond Activation J. Am. Chem. Soc127 13496CrossRefGoogle Scholar
  20. 20.
    (a) Thalji R K, Ahrendt K A, Bergman R G and Ellman J A 2001 Annulation of Aromatic Imines via Directed C-H Activation with Wilkinson’s Catalyst J. Am. Chem. Soc123 9692; (b) Ahrendt K A, Bergman R G and Ellman J A 2003 Synthesis of a Tricyclic Mescaline Analogue by Catalytic C-H Bond Activation Org. Lett5 1301Google Scholar
  21. 21.
    Wang D H and Yu J Q 2011 Highly Convergent Total Synthesis of (+)-Lithospermic Acid via a Late-Stage Intermolecular C-H Olefination J. Am. Chem. Soc133 5767CrossRefGoogle Scholar
  22. 22.
    Hrdina R, Metz F M, Larrosa M, Berndt J–P, Zhygadlo Y, Becker S and Becker J 2015 Intramolecular C–H Amination Reaction Provides Direct Access to 1,2-Disubstituted Diamondoids Eur. J. Org. Chem28 6231CrossRefGoogle Scholar
  23. 23.
    (a) Fokin A A, Schreiner P R, Gunchenko P A, Peleshanko S A, Shubina T E, Isaev S D, Tarasenko P V, Kulik N I, Schiebel H M and Yurchenko A G 2000 Oxidative Single-Electron Transfer Activation of \(\upsigma \)-Bonds in Aliphatic Halogenation Reactions J. Am. Chem. Soc. 122 7317; (b) Roizen J L, Zalatan D N and Du Bois J 2013 Selective intermolecular amination of C-H bonds at tertiary carbon centers Angew. Chem. Int. Edit52 11343Google Scholar
  24. 24.
    (a) Seki M and Nagahama M 2011 Synthesis of angiotensin II receptor blockers by means of a catalytic system for C-H activation J. Org. Chem76 10198; (b) Lutz A 2015 Robust Ruthenium(II)-Catalyzed C-H Arylations: Carboxylate Assistance for the Efficient Synthesis of Angiotensin-II-Receptor Blockers Org. Process Res. Dev19 260Google Scholar
  25. 25.
    (a) Larsen R D, King A O, Chen C Y, Corley E G, Foster B S, Roberts F E, Yang C, Lieberman D R, Reamer R A, Tschaen D M, Verhoeven T R, Reider P J, Lo Y S, Rossano L T, Brookes S, Meloni D, Moore J R and Arnett J F 1994 Efficient Synthesis of Losartan, A Nonpeptide Angiotensin II Receptor Antagonist J. Org. Chem. 59 6391; (b) Beutler U, Boehm M, Fuenfschilling P C, Heinz T, Mutz J P, Onken U, Mueller M and Zaugg W 2007 A High-Throughput Process for Valsartan Org. Process Res. Dev11 892; (c) Kumar N, Reddy S B, Sinha B K, Mukkanti K and Dandala R 2009 New and Improved Manufacturing Process for Valsartan Org. Process Res. Dev.  13 1185; (d) Wang G X, Sun B P and Peng C H 2011 An Improved Synthesis of Valsartan Org. Process Res. Dev15 986Google Scholar
  26. 26.
    Ouellet S G, Roy A, Molinaro C, Angelaud R, Marcoux J F, O’Shea P D and Davies I W 2011 Preparative scale synthesis of the biaryl core of anacetrapib via a ruthenium-catalyzed direct arylation reaction: unexpected effect of solvent impurity on the arylation reaction J. Org. Chem76 1436CrossRefGoogle Scholar
  27. 27.
    Lutz A, Vicente R, Potukuchi H K and Pirovano V 2010 Mechanistic Insight into Direct Arylations with Ruthenium(II) Carboxylate Catalysts Org. Lett. 12 5032CrossRefGoogle Scholar
  28. 28.
    Campbell A N, Cole K P, Martinelli J R, May S A, Mitchell D, Pollock P M and Sullivan K A 2013 Development of an Alternate Synthesis for a Key JAK2 Inhibitor Intermediate via Sequential C-H Bond Functionalization Org. Process Res. Dev17 273CrossRefGoogle Scholar
  29. 29.
    Mitchell D, Cole K P, Pollock P M, Coppert D M, Burkholder T P and Clayton J R 2012 Development and a Practical Synthesis of the JAK2 Inhibitor LY2784544 Org. Process Res. Dev. 16 70CrossRefGoogle Scholar
  30. 30.
    (a) Fürstner A, Domostoj M M and Scheiper B 2005 Total Synthesis of Dictyodendrin B J. Am. Chem. Soc. 127 11620; (b) Hirao S, Sugiyama Y, Iwao M and Ishibashi F 2009 Synthetic Approach to Telomerase Inhibitor Dictyodendrin B: Synthesis of the Pyrrolo[2,3-c]carbazole Core Biosci. Biotechnol. Biochem73 1764; (c) Okano K, Fujiwara H, Noji T, Fukuyama T and Tokuyama H 2010 Total Synthesis of Dictyodendrin A and B Angew. Chem. Int. Edit. 49 5925; (d) Liang J, Hu W, Tao P and Jia Y 2013 Total Synthesis of Dictyodendrins B and E J. Org. Chem78 5810Google Scholar
  31. 31.
    Pitts A K, O’Hara F, Snell R H and Gaunt M J 2015 A Concise and Scalable Strategy for the Total Synthesis of Dictyodendrin B Based on Sequential CH Functionalization Angew. Chem127 5541Google Scholar

Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  1. 1.Integrated Product Development, Innovation PlazaDr. Reddy’s Laboratories Ltd.Ranga Reddy DistrictIndia

Personalised recommendations