Copper-Catalyzed Regioselective Cyanation of Indoles via C-H Bond Activation with α-Aminoacetonitriles

Abstract

A metal-free and organic cyanating agent, 2-(diisopropylamino)acetonitrile is disclosed for the regioselective synthesis of cyanated indoles such as 2-cyanoindole and 3-cyanoindole derivatives. This method can tolerate a variety of functional groups and can furnish the corresponding cyanated products in moderate to high yields. Moreover, Cu/PhSiH₃ system has been identified for the regioselective cleavage of C–H bonds of indoles by the use of metal-free CN sources via a one-pot sequential iodination/cyanation. This cost effective, homogeneous and metal-free CN source system represents the best reaction efficiency in these methodologies.

Keywords

cyanation - iodination - indole - Cu-catalyst - regioselectivity

Publication History

Received: 20 March 2023

Accepted after revision: 08 May 2023

Accepted Manuscript online:
08 May 2023

Article published online:
03 July 2023

• References

• 1a Gribble GW. Topics in Heterocyclic Chemistry, Vol. 26. Maes BU. W. Springer; New York: 2010
• 1b Rodrigues de Sa Alves F, Barreiro EJ, Fraga CA. M. Mini-Rev. Med. Chem. 2009; 9: 782
• 1c Crich D, Banerjee A. Acc. Chem. Res. 2007; 40: 151
• 1d Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
• 1e Cacchi S, Fabrizi G. Chem. Rev. 2005; 105: 2873
• 2 Rhoennstad P, Kallin E, Apelqvist T, Wennerstaal M, Cheng A. PCT Int. Appl WO 2009127686 A1 20091022, 2009
• 3a The Chemistry of the Cyano Group . Rappoport Z. Wiley Interscience; London: 1970
• 3b Larock RC. Comprehensive Organic Transformations: A Guide to Functional Group Preparations. Wiley-VCH; New York: 1989
• 4a Sandmeyer T. Ber. Dtsch. Chem. Ges. 1884; 17: 1633
• 4b Kochi JK. J. Am. Chem. Soc. 1957; 79: 2942
• 4c Lindley J. Tetrahedron 1984; 40: 1433
• 4d See review: Hodgson HH. Chem. Rev. 1947; 40: 251 (5)
• 4e Rosenmund K, Struck WE. Ber. Dtsch. Chem. Ges. 1919; 52: 1749
• 4f Koelsch CF, Whitney AG. J. Org. Chem. 1941; 6: 795
• 4g Review: Galli C. Chem. Rev. 1988; 88: 765
• 4h Review: Merkushev EB. Synthesis 1988; 923: 6

For recent examples, see:
• 4i Zanon J, Klapars A, Buchwald SL. J. Am. Chem. Soc. 2003; 125: 10
• 5a Kleemann A, Engel J, Kutscher B, Reichert D. Pharmaceutical Substance: Synthesis, Patents, Applications, 4th ed. Thieme; Stuttgart: 2001
• 5b Larock RC. In Comprehensive Organic Transformations: A Guide to Functional Group Preparations. Wiley-VCH; Weinheim: 1989: 819-995
• 6 Anbarasan P, Schareina T, Beller M. Chem. Soc. Rev. 2011; 40: 5049
• 7a Sandmeyer T. Ber. Dtsch. Chem. Ges. 1885; 18: 1946
• 7b Sandmeyer T. Ber. Dtsch. Chem. Ges. 1885; 18: 1492
• 7c Sandmeyer T. Ber. Dtsch. Chem. Ges. 1884; 17: 2650
• 8a Sakamoto T, Ohsawa K. J. Chem. Soc., Perkin Trans. 1 1999; 2323
• 8b Sakakibara Y, Okuda F, Shimobayashi A, Kirino K, Sakai M, Uchino N, Takagi K. Bull. Chem. Soc. Jap. 1988; 61: 1985
• 8c Percec V, Bae J.-Y, Hill DH. J. Org. Chem. 1995; 60: 6895
• 8d Anderson BA, Bell EC, Ginah FO, Harn NK, Pagh LM, Wepsiec JP. J. Org. Chem. 1998; 63: 8224
• 8e Yang C, Williams JM. Org. Lett. 2004; 6: 2837
• 8f Cristau HJ, Ouali A, Spindler JF, Taillefer M. Chem. Eur. J. 2005; 11: 2483
• 8g Okano T, Iwahara M, Kiji J. Synlett 1998; 243
• 8h Zanon J, Klapars A, Buchwald SL. J. Am. Chem. Soc. 2003; 125: 2890
• 8i Maligres PE, Waters MS, Fleitz F, Askin D. Tetrahedron Lett. 1999; 40: 8193
• 8j Chidambaram R. Tetrahedron Lett. 2004; 45: 1441
• 8k Jensen RS, Gajare AS, Toyota K, Yoshifuji M, Ozawa F. Tetrahedron Lett. 2005; 46: 8645
• 8l Littke A, Soumeillant M, Kaltenbach RF, Cherney RJ, Tarby CM, Kiau S. Org. Lett. 2007; 9: 1711
• 8m Martin MT, Liu B, Cooley BE, Eaddy JF. Tetrahedron Lett. 2007; 48: 2555
• 8n Buono FG, Chidambaram R, Mueller RH, Waltermire RE. Org. Lett. 2008; 10: 5325
• 9a Zhu Y, Zhao M, Lu W, Li L, Shen Z. Org. Lett. 2015; 17: 2602
• 9b Zhu Y, Li L, Shen Z. Chem. Eur. J. 2015; 21: 13246

For reviews on C–H activation, see:
• 10a Labinger JA, Bercaw JE. Nature 2002; 417: 507
• 10b Bergman RG. Nature 2007; 446: 391
• 10c Kakiuchi F, Kochi T. Synthesis 2008; 3013
• 10d Yamaguchi J, Yamaguchi AD, Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
• 10e Wencel-Delord J, Glorius F. Nat. Chem. 2013; 5: 369
• 10f Zhou L, Lu W. Chem. Eur. J. 2014; 20: 634
• 10g Girard SA, Knauber T, Li C.-J. Angew. Chem. Int. Ed. 2014; 53: 74
• 10h Ahmad MS, Meguellati K. ChemistrySelect 2022; 7: e202103716
• 11 Mengdi Z, Wei Z, Zengming S. J. Org. Chem. 2015; 80: 8868
• 12a Kim J, Choi J, Shin K, Chang S. J. Am. Chem. Soc. 2012; 134: 2528
• 12b Zhang G, Ren X, Chen J, Hu M, Cheng J. Org. Lett. 2011; 13: 5004
• 13 Ahmad MS, Shafiq Z, Meguellati K. Synthesis 2022; 54: 3077
• 14 Xuezhen K, Mengdi Z, Xixue Q, Yamin Z, Xiaofeng T, Zengming S. Chem. Eur. J. 2013; 19: 16880