Synthesis of Heteroarylogous 1H-Indole-3-carboxamidines via a Three-Component Interrupted Ugi Reaction

Fabio La Spisa; Fiorella Meneghetti; Beatrice Pozzi; Gian Cesare Tron

doi:10.1055/s-0034-1378921

Synthesis, Table of Contents

Synthesis 2015; 47(04): 489-496
DOI: 10.1055/s-0034-1378921

paper

Synthesis of Heteroarylogous 1H-Indole-3-carboxamidines via a Three-Component Interrupted Ugi Reaction

Authors

Fabio La Spisa

^aDipartimento di Scienze del Farmaco, Università del Piemonte Orientale ‘A. Avogadro’, Largo Donegani 2, 28100 Novara, Italy Fax: +39(0321)375621 Email: giancesare.tron@unipmn.it
Fiorella Meneghetti

^bDipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy
Beatrice Pozzi

^aDipartimento di Scienze del Farmaco, Università del Piemonte Orientale ‘A. Avogadro’, Largo Donegani 2, 28100 Novara, Italy Fax: +39(0321)375621 Email: giancesare.tron@unipmn.it
Gian Cesare Tron*

^aDipartimento di Scienze del Farmaco, Università del Piemonte Orientale ‘A. Avogadro’, Largo Donegani 2, 28100 Novara, Italy Fax: +39(0321)375621 Email: giancesare.tron@unipmn.it

Abstract

All articles of this category

Abstract

A novel one-pot multicomponent synthesis of heteroarylogous 1H-indole-3-carboxamidines starting from readily available N-alkyl-N-(1H-indol-2-ylmethyl)amines, isocyanides, and carbonyl compounds is reported. The strategy exploits the ability of the indole nucleus to interrupt the classical Ugi reaction, by intercepting the nascent nitrilium ion.

Key words

isocyanides - secondary amines - Ugi reaction - multicomponent reactions - indoles

Full Text

References

References
1 Ugi I, Meyr U, Steinbrückner A. Angew. Chem. 1959; 71: 386
2 Chéron N, Ramozzi R, El Kaïm L, Grimaud L, Fleurat-Lessard P. J. Org. Chem. 2012; 77: 1361
3 Multicomponent Reactions . Zhu J, Bienaymé H. Wiley-VCH; Weinheim: 2005
4 Zinner G, Moderhack D, Kliegel W. Chem. Ber. 1969; 102: 2536
5 Ugi I, Bodesheim F. Chem. Ber. 1961; 94: 2797
6 Ugi I, Rosendhal FK, Bodesheim F. Justus Liebigs Ann. Chem. 1963; 666: 54
7 Ugi I, Offermann K. Chem. Ber. 1964; 97: 2996

For interesting reviews, see:

8a Ganem B. Acc. Chem. Res. 2009; 42: 463
8b El Kaïm L, Grimaud L. Tetrahedron 2009; 65: 2153

9 Tron GC. Eur. J. Org. Chem. 2013; 1849
10 El Kaïm L, Gizolme M, Grimaud L, Oble J. J. Org. Chem. 2007; 72: 4169
11 Oaksmith JM, Peters U, Ganem B. J. Am. Chem. Soc. 2004; 126: 13606
12 Soeta T, Kojima Y, Ukaji Y, Inomata K. Org. Lett. 2010; 12: 4341
13 Neidlein R. Z. Naturforsch., B 1964; 19: 1159
14 Pirali T, Mossetti R, Galli S, Tron GC. Org. Lett. 2011; 13: 3734

15a Sun X, Janvier P, Zhao G, Bienaymé H, Zhu J. Org. Lett. 2001; 3: 877

For an excellent review, see:

15b Gulevich AV, Zhdanko AG, Orru RV. A, Nenajdenko VG. Chem. Rev. 2010; 110: 5235

16 Lalli C, Bouma MJ, Bonne D, Masson G, Zhu J. Chem. Eur. J. 2011; 17: 880

17a Kysil V, Khvat A, Tsirulnikov S, Tkachenko S, Williams C, Churakova M, Ivachtchenko A. Eur. J. Org. Chem. 2010; 1525
17b Keung W, Bakir F, Patron A, Rogers D, Priest CD, Darmohusodo V. Tetrahedron Lett. 2004; 45: 733

18a Deyrup JA, Vestling MM, Hagan WV, Yun HY. Tetrahedron 1969; 25: 1467
18b Schneekloth JS, Kim J, Sorensen EJ. Tetrahedron 2009; 65: 3096
18c Kim J, Schneekloth JS, Sorensen EJ. Chem. Sci. 2012; 3: 2849

19 Varadi A, Palmer TC, Notis PR, Redel-Traub GN, Afonin D, Subrath JJ, Pasternak GW, Hu C, Sharma I, Majumdar S. Org. Lett. 2014; 16: 1668

20a Bienaymé H, Bouzid K. Angew. Chem. 1998; 110: 2349
20b Groebke K, Weber L, Mehlin F. Synlett 1998; 661
20c Blackburn B, Guan P, Fleming K, Shiosaki S, Tsai S. Tetrahedron Lett. 1998; 39: 3635

Vinylogous amidines have been described; see:

21a LaBarbera DV, Skibo EB. J. Org. Chem. 2013; 78: 11887
21b Gartshore GJ, Lupton DW. Angew. Chem. Int. Ed. 2013; 52: 4113

22 CCDC 1003584 contains the supplementary crystallographic data for compound 11 reported in this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
23 Cremer D, Pople JA. J. Am. Chem. Soc. 1975; 97: 1354
24 Farrugia LJ. J. Appl. Crystallogr. 2012; 45: 849

For an example of interception of the nitrilium ion by the C3 of indole, see:

25a Wang X, Wang SY, Ji SJ. Org. Lett. 2013; 15: 1954
25b Kobayashi K, Izumi Y, Hayashi K, Morikawa O, Konishi H. Bull. Chem. Soc. Jpn. 2005; 78: 2171

26 Hegarthy AF. Acc. Chem. Res. 1980; 13: 448

To the best of our knowledge, only some work where the pyrrole ring was able to trap the nitrilium ion has been described, by the Kobayashi group; see:

27a Kobayashi K, Matsumoto T, Irisawa S, Yoneda K, Morikawa O, Konishi H. Heterocycles 2001; 55: 973
27b Kobayashi K, Takanohashi A, Hashimoto K, Morikawa O, Konishi H. Tetrahedron 2006; 62: 10379
27c Kobayashi K, Himei Y, Izumi Y, Fukamachi S, Morikawa O, Konishi H. Heterocycles 2007; 71: 691

28 Miller WH, Newlander KA, Seefeld MA, Uzinskas IN, DeWolf WE, Jakas DR. PCT Int. Appl WO 2001027103, 2001
29 Bandini M, Melloni A, Umani-Ronchi A. Org. Lett. 2004; 6: 3199

Supplementary Material

Supporting Information (PDF)