Regioselective Direct C–H Alkylation of NH Indoles and Pyrroles by a Palladium/Norbornene-Cocatalyzed Process

Lei Jiao; Thorsten Bach

doi:10.1055/s-0033-1338523

Synthesis, Table of Contents

Synthesis 2014; 46(01): 35-41
DOI: 10.1055/s-0033-1338523

practical synthetic procedures

Regioselective Direct C–H Alkylation of NH Indoles and Pyrroles by a Palladium/Norbornene-Cocatalyzed Process

Authors

Lei Jiao

Lehrstuhl für Organische Chemie I and Catalysis Research Center (CRC), Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany Fax: +49(89)28913315 Email: thorsten.bach@ch.tum.de
Thorsten Bach*

Lehrstuhl für Organische Chemie I and Catalysis Research Center (CRC), Technische Universität München, Lichtenbergstr. 4, 85747 Garching, Germany Fax: +49(89)28913315 Email: thorsten.bach@ch.tum.de

Abstract

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Abstract

Nitrogen-containing heterocycles, including 1H-indoles and electron-deficient 1H-pyrroles, undergo a palladium/norbornene-cocatalyzed regioselective alkylation at the C–H bond adjacent to the NH group. A primary alkyl halide is used as the electrophile and the reaction proceeds smoothly under mild conditions to give 2-alkyl-1H-indoles and 2-substituted or 2,3-disubstituted 5-alkyl-1H-pyrroles in good yields.

Key words

catalysis - alkylations - regioselectivity - heterocycles - palladium - indoles - pyrroles

Full Text

References

References

1a Sundberg RJ. Indoles . Academic Press; San Diego: 1996
1b Sundberg RJ In Comprehensive Heterocyclic Chemistry II . Vol. 2. Katritzky AR, Rees CW, Scriven EF. V. Pergamon; Oxford: 1996: 119
1c Joule JA In Science of Synthesis, Thomas E. J. Vol. 10. Thieme; Stuttgart: 2000: 361
1d Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000; 1045
1e Tois J, Franzén R, Koskinen A. Tetrahedron 2003; 59: 5395
1f d’Ischia M, Napolitano A, Pezzella A In Comprehensive Heterocyclic Chemistry III . Vol. 3. Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Elsevier; Amsterdam: 2008. Chap. 1–4

2a Atta-ur-Rahman, Basha A. Indole Alkaloids . Harwood Academic; Amsterdam: 1997
2b Gribble GW In Rodd’s Chemistry of Carbon Compounds . 2nd ed., Suppl. 2, Vol. IV; Sainsbury M. Elsevier; Amsterdam: 1997. Chap. 9, 69
2c Mal D, Shome B, Dinda BK In Heterocycles in Natural Product Synthesis . Majumdar KC, Chattopadhyay SK. Wiley-VCH; Weinheim: 2011: 187

For reviews, see:

3a Cacchi S, Fabrizi G. Chem. Rev. 2005; 105: 2873
3b Seregin IV, Gevorgyan V. Chem. Soc. Rev. 2007; 36: 1173
3c Joucla L, Djakovitch L. Adv. Synth. Catal. 2009; 351: 673
3d Bandini M, Eichholzer A. Angew. Chem. Int. Ed. 2009; 48: 9608
3e Beck EM, Gaunt MJ. Top. Curr. Chem. 2010; 292: 85
3f Broggini G, Beccalli EM, Fasana A, Gazzola S. Beilstein J. Org. Chem. 2012; 8: 1730

4 Joule JA, Mills K. Heterocyclic Chemistry . 5th ed. Wiley; Chichester: 2010: 373

The direct C2 functionalization of indole can be achieved through C2-lithiation of N-protected indoles. For examples, see:

5a Shirley DA, Roussel PA. J. Am. Chem. Soc. 1953; 75: 375
5b Sundberg RJ, Russell HF. J. Org. Chem. 1973; 38: 3324
5c Hasan I, Marinelli ER, Lin LC, Fowler FW, Levy AB. J. Org. Chem. 1981; 46: 157
5d Katritzky AR, Akutagawa K. Tetrahedron Lett. 1985; 26: 5935
5e Gharpure M, Stoller A, Bellamy F, Firnau G, Snieckus V. Synthesis 1991; 1079
5f Fukuda T, Mine Y, Iwao M. Tetrahedron 2001; 57: 975
5g De Simone F, Gertsch J, Waser J. Angew. Chem. Int. Ed. 2010; 49: 5767

6a Nakao Y, Kashihara N, Kanyiva KS, Hiyama T. Angew. Chem. Int. Ed. 2010; 49: 4451
6b Nagib DA, MacMillan DW. C. Nature (London) 2011; 480: 224
6c Lee D.-H, Kwon K.-H, Yi CS. Science (Washington D. C.) 2011; 333: 1613
6d Ding Z, Yoshikai N. Beilstein J. Org. Chem. 2012; 8: 1536
6e Pan S, Ryu N, Shibata T. J. Am. Chem. Soc. 2012; 134: 17474

7a Skell PS, Bean GP. J. Am. Chem. Soc. 1962; 84: 4655
7b Griffin CE, Obrycki R. J. Org. Chem. 1964; 29: 3090
7c Castro AJ, Deck JF, Ling NC, Marsh JP. Jr, Means GE. J. Org. Chem. 1965; 30: 344
7d Bean GP. J. Org. Chem. 1967; 32: 228
7e Papadopoulos EP, Tabello KI. Y. J. Org. Chem. 1968; 33: 1299
7f Reinecke MG, Sebastian JF, Johnson HW. Jr, Pyun C. J. Org. Chem. 1972; 37: 3066
7g Wang N.-C, Teo K.-E, Anderson HJ. Can. J. Chem. 1977; 55: 4112

For selected recent examples of direct alkylation of pyrroles, see:

8a Guerrero MA, Miranda LD. Tetrahedron Lett. 2006; 47: 2517
8b Guadarrama-Morales O, Méndez F, Miranda LD. Tetrahedron Lett. 2007; 48: 4515
8c Trost BM, Müller C. J. Am. Chem. Soc. 2008; 130: 2438
8d Sheng Y.-F, Gu Q, Zhang A.-J, You S.-L. J. Org. Chem. 2009; 74: 6899
8e Zaitsev AB, Gruber S, Plüss PA, Pregosin PS, Veiros LF, Wörle M. J. Am. Chem. Soc. 2008; 130: 11604
8f Liu Y, Cao Z, Du H. J. Org. Chem. 2012; 77: 4479
8g Jorapur YR, Lee C.-H, Chi DY. Org. Lett. 2005; 7: 1231
8h Jorapur YR, Chi DY. Bull. Korean Chem. Soc. 2011; 32: 3130

For reviews, see:

9a Catellani M. Synlett 2003; 298
9b Catellani M. Top. Organomet. Chem. 2005; 14: 21
9c Catellani M, Motti E, Della Ca’ N. Acc. Chem. Res. 2008; 41: 1512
9d Martins A, Mariampillai B, Lautens M. Top. Curr. Chem. 2010; 292: 1

10a Jiao L, Bach T. J. Am. Chem. Soc. 2011; 133: 12990
10b Jiao L, Herdtweck E, Bach T. J. Am. Chem. Soc. 2012; 134: 14563

11 Jiao L, Bach T. Angew. Chem. Int. Ed. 2013; 52: 6080
12 Bordwell FG. Acc. Chem. Res. 1988; 21: 456

For selected examples, see:

13a Cambie RC, Moratti SC, Rutledge PS, Woodgate PD. Synth. Commun. 1990; 20: 1923
13b Rolfs A, Liebscher J. Angew. Chem. Int. Ed. Engl. 1993; 32: 712
13c Hwang SH, Kurth MJ. Tetrahedron Lett. 2002; 43: 53
13d Bellur E, Langer P. Tetrahedron Lett. 2006; 47: 2151
13e Lygin AV, Larionov OV, Korotkov VS, de Meijere A. Chem. Eur. J. 2009; 15: 227
13f Bellur E, Yawer MA, Hussain I, Riahi A, Fatunsin O, Fischer C, Langer P. Synthesis 2009; 227
13g Hekmatshoar R, Sadjadi S, Sadjadi S, Heravi MM, Beheshtiha YS, Bamoharram FF. Synth. Commun. 2010; 40: 1708