Pd-Catalyzed Cyclization of 1-Allyl-2-indolecarboxamides by Intramolecular Amidation of Unactivated Ethylenic Bond

Giorgio Abbiati; Egle Beccalli; Gianluigi Broggini; Michela Martinelli; Giuseppe Paladino

doi:10.1055/s-2005-922788

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2006(1): 0073-0076
DOI: 10.1055/s-2005-922788

LETTER

Pd-Catalyzed Cyclization of 1-Allyl-2-indolecarboxamides by Intramolecular Amidation of Unactivated Ethylenic Bond

Giorgio Abbiati^a, Egle Beccalli^a, Gianluigi Broggini*^b, Michela Martinelli^a, Giuseppe Paladino^a
^a Istituto di Chimica Organica ‘A. Marchesini’, Facoltà di Farmacia, Università di Milano, via Venezian 21, 20133 Milan, Italy
^b Dipartimento di Scienze Chimiche e Ambientali, Università dell’Insubria, via Valleggio 11, 22100 Como, Italy
Fax: +39(31)2386449; e-Mail: gianluigi.broggini@uninsubria.it;

Further Information

Publication History

Received 4 October 2005
Publication Date:
16 December 2005 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

The intramolecular Pd(II)-mediated cyclization of 1-allyl-2-indolecarboxamides leads to pyrazino[1,2-a]indoles through the conversion of the olefinic C-H bond into a C-N bond by reaction with an amide group. When operating on the allylamide, a domino process was observed with a double C-H functionalization.

Key words

cyclizations - fused-ring systems - indoles - palladium - domino reactions

References and Notes

For reviews, see:
1a Wolfe JP. Wagaw S. Marcoux J.-F. Buchwald SL. Acc. Chem. Res. 1998, 31: 805

Crossref PubMed Google Scholar
1b Hartwig JF. Angew. Chem. Int. Ed. 1998, 37: 2046

Crossref PubMed Google Scholar
2a Sigman MS. Schultz MJ. Org. Biomol. Chem. 2004, 2: 2551

Google Scholar
2b Bar GLJ. Lloyd-Jones GC. Booker-Milburn KI. J. Am. Chem. Soc. 2005, 127: 7308

Google Scholar
2c Brice JL. Harang JE. Timokhin VI. Anastasi NR. Stahl SS. J. Am. Chem. Soc. 2005, 127: 2868

Google Scholar
2d Timokhin VI. Anastasi NR. Stahl SS. J. Am. Chem. Soc. 2003, 125: 12996

Google Scholar
2e Gowan M. Caillé AS. Lau CK. Synlett 1997, 1312

Google Scholar
2f Andersson PG. Bäckvall J.-E. J. Am. Chem. Soc. 1992, 114: 8696

Google Scholar
2g Bäckvall J.-E. Andersson PG. J. Am. Chem. Soc. 1990, 112: 3683

Google Scholar
2h Pugin B. Venanzi LM. J. Am. Chem. Soc. 1983, 105: 6877

Google Scholar
2i Hegedus LS. Allen GF. Bozell JJ. Waterman EL. J. Am. Chem. Soc. 1978, 100: 5800

Google Scholar
3 Li JJ. Gribble GW. Palladium in Heterocyclic Chemistry, A Guide for the Synthetic Chemist Pergamon; New York: 2000.

Google Scholar
For recent contributions, see:
4a Cacchi S. Fabrizi G. Chem. Rev. 2005, 105: 2873

Article in Thieme Connect Google Scholar
4b Capito E. Brown JM. Ricci A. Chem. Commun. 2005, 1854

Article in Thieme Connect Google Scholar
4c Grimster NP. Gauntlett C. Godfrey CRA. Gaunt MJ. Angew. Chem. Int. Ed. 2005, 44: 3125

Article in Thieme Connect Google Scholar
4d Cacchi S. Fabrizi G. Parisi LM. Synthesis 2004, 1889

Article in Thieme Connect Google Scholar
4e Siebeneicher H. Bytschkov I. Doye S. Angew. Chem. Int. Ed. 2003, 42: 3042

Article in Thieme Connect Google Scholar
4f Willis MC. Brace GN. Holmes IP. Angew. Chem. Int. Ed. 2005, 44: 403

Article in Thieme Connect Google Scholar
4g Watanabe T. Arai S. Nishida A. Synlett 2004, 907

Article in Thieme Connect Google Scholar
5a Sundberg RJ. Indoles Academic Press; London: 1996.

Crossref Google Scholar
5b Knölker H.-J. Reddy KR. Chem. Rev. 2002, 102: 4303

Crossref Google Scholar
5c Gilchrist TL. J. Chem. Soc., Perkin Trans. 1 1999, 2848

Crossref Google Scholar
5d Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000, 1045

Crossref Google Scholar
5e Bräse S. Gil C. Knepper K. Bioorg. Med. Chem. 2002, 10: 2415

Crossref Google Scholar
6a Beccalli EM. Broggini G. Marchesini A. Rossi E. Tetrahedron 2002, 58: 6673

Crossref PubMed Google Scholar
6b Beccalli EM. Broggini G. Tetrahedron Lett. 2003, 44: 1919

Crossref PubMed Google Scholar
6c Abbiati G. Beccalli EM. Broggini G. Zoni C. J. Org. Chem. 2003, 68: 7625

Crossref PubMed Google Scholar
6d
Abbiati, G.; Beccalli, E. M.; Broggini, G.; Paladino, G.; Rossi, E. Synthesis, in press.

Crossref PubMed
7a Tiwari RK. Singh J. Singh D. Verma AK. Chandra R. Tetrahedron 2005, 61: 9513

Crossref Google Scholar
7b Abbiati G. Arcadi A. Bellinazzi A. Beccalli EM. Rossi E. Zanzola S. J. Org. Chem. 2005, 70: 4088

Crossref Google Scholar
8a Ruppelt M, Bartel S, Guarnieri W, Raddatz S, Rosentreter U, Wild H, Endermann R, and Kroll HP. inventors; Ger. Offen. DE 19802235. ; Chem. Abstr. 1999, 131, 129985
9a Davis PD, Hill CH, and Lawton G. inventors; Eur. Pat. 384349. ; Chem. Abstr. 1991, 114, 81582p

Crossref
9b Bit RA. Davis PD. Elliott LH. Harris W. Hill CH. Keech E. Kumar H. Lawton G. Maw A. Nixon JS. Vesey DR. Wadsworth J. Wilkinson SE. J. Med. Chem. 1993, 36: 21

Crossref Google Scholar
10 Wyss PC. Gerber P. Hartman PG. Hubschwerlen C. Locher H. Marty H.-P. Stahl M. J. Med. Chem. 2003, 46: 2304

Crossref Google Scholar
11 McCort G, Hoornaert C, Duclos O, Guilpain E, Cadilhac C, and Dellac G. inventors; Fr. Patent FR 2 761 073. ; Chem. Abstr. 1999, 130, 384000
12 Tapia RA. Prieto Y. Pautet F. Domard M. Sarciron M.-E. Walchshofer N. Fillion H. Eur. J. Org. Chem. 2002, 4005

Crossref Google Scholar
13 Vigushin DM. Brooke G. Willows D. Coombes RC. Moody CJ. Bioorg. Med. Chem. Lett. 2003, 13: 3661

Crossref Google Scholar
14 Chang-Fong J. Addo J. Dukat M. Smith C. Mitchell NA. Herrick-Davis K. Teitler M. Glennon RA. Bioorg. Med. Chem. Lett. 2002, 12: 155

Crossref Google Scholar
15 Padwa A. Hertzog DL. Nadler WR. Osterhout MH. Price AT. J. Org. Chem. 1994, 59: 1418

Crossref Google Scholar
17 Jeffery T. Tetrahedron 1996, 30: 10113

Google Scholar
19 Chacun-Lefèvre L. Bénéteau V. Joseph B. Mérour J.-Y. Tetrahedron 2002, 58: 10181

Crossref Google Scholar
21a Kasahara A. Izumi T. Murakami S. Miyamoto K. Hino T. J. Heterocycl. Chem. 1989, 26: 1405

Crossref Google Scholar
21b Izumi T. Nishimoto Y. Kohei K. Kasahara A. J. Heterocycl. Chem. 1990, 27: 1419

Crossref Google Scholar
22a Alexanian EJ. Lee C. Sorensen EJ. J. Am. Chem. Soc. 2005, 127: 7690

Google Scholar
22b Beccalli EM. Broggini G. Paladino G. Penoni A. Zoni C. J. Org. Chem. 2004, 69: 5627

Google Scholar
22c Fix SR. Brice JL. Stahl SS. Angew. Chem. Int. Ed. 2002, 41: 164

Google Scholar
22d Larock RC. Hightower TR. Hasvold LA. Peterson KP. J. Org. Chem. 1996, 61: 3584

Google Scholar
22e Rönn M. Bäckvall J.-E. Andersson PG. Tetrahedron Lett. 1995, 36: 7749

Google Scholar
22f Hegedus LS. McKearin JM. J. Am. Chem. Soc. 1982, 104: 2444

Google Scholar

16

Experimental Procedure.
A suspension of 2a (276 mg, 1.0 mmol), Pd(OAc)₂ (11 mg, 0.05 mmol), Na₂CO₃ (318 mg, 3.0 mmol), Bu₄NCl (278 mg, 1.0 mmol) and p-benzoquinone (108 mg, 1 mmol) in DMF (10 mL) was stirred for 24 h at 100 °C. The solution was washed with brine (25 mL) and extracted with Et₂O (2 × 25 mL). The organic layer was dried over Na₂SO₄ and taken to dryness under reduced pressure. The residue was chromatographed on a silica gel column with light PE-EtOAc 12:1 as eluent to give 3a.
Data for 3-Methyl-2-phenyl-2 H -pyrazino[1,2- a ]indol-1-one (3a).
Mp 249-250 °C (diisopropyl ether). IR (nujol): 1682 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.95 (3 H, s), 7.24 (1 H, s), 7.29-7.34 (3 H, m), 7.39-7.45 (2 H, m), 7.48-7.56 (3 H, m), 7.68 (1 H, d, J = 8.2 Hz), 7.85 (1 H, d, J = 8.1 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 18.7 (q), 103.5 (d), 104.1 (d), 110.8 (d), 122.6 (d), 123.0 (s), 123.1 (d), 124.3 (d), 127.4 (s), 128.0 (s), 129.1 (d), 129.4 (d), 129.9 (d), 132.3 (s), 137.9 (s), 158.4 (s). MS: m/z = 274 [M⁺]. Anal. Calcd for C₁₈H₁₄N₂O: C, 78.81; H, 5.14; N, 10.21. Found: C, 78.97; H, 4.99; N, 10.32.

18

3-Methyl-2-(pyridin-2-yl)-3,4-dihydro-2 H -pyrazino[1,2- a ]indol-1-one (8).
Mp 198-199 °C (diisopropyl ether). IR (nujol): 1678 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.46 (3 H, d, J = 6.7 Hz), 4.32 (1 H, d, J = 12.0 Hz), 4.44 (1 H, dd, J = 4.0, 12.0 Hz), 5.43-5.51 (1 H, m), 7.13 (1 H, dd, J = 5.0, 7.0 Hz), 7.18-7.24 (1 H, m), 7.34-7.44 (2 H, m), 7.45 (1 H, s), 7.71-7.80 (2 H, m), 8.17 (1 H, d, J = 8.4 Hz), 8.47 (1 H, d, J = 4.0 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 19.3 (q), 46.4 (t), 51.5 (d), 107.9 (d), 110.1 (d), 120.1 (d), 120.7 (d), 121.2 (d), 123.2 (d), 125.3 (d), 128.0 (s), 129.2 (s), 137.3 (s), 137.7 (d), 148.1 (d), 152.9 (s), 159.7 (s). MS: m/z = 277 [M⁺]. Anal. Calcd for C₁₇H₁₅N₃O: C, 73.63; H, 5.45; N, 15.15. Found: C, 73.51; H, 5.27; N, 15.01.

20

2-Methyl-12,12a-dihydro-1 H -pyrrolo[1′,2′:4,5]pyr-azino[1,2- a ]indol-5-one (10).
Oil. IR (nujol): 1657 cm^-1. ¹H NMR (400 MHz, DMSO): δ = 1.83 (3 H, s), 2.59-2.69 (1 H, m), 2.78 (1 H, dd, J = 9.2, 15.9 Hz), 3.97 (1 H, dd, J = 12.1, 12.2 Hz), 4.52-4.65 (1 H, m), 4.92 (1 H, dd, J = 4.4, 12.1 Hz), 6.80 (1 H, s), 7.08 (1 H, s), 7.12 (1 H, dd, J = 7.7, 8.3 Hz), 7.31 (1 H, dd, J = 7.7, 8.0 Hz), 7.57 (1 H, d, J = 8.3 Hz), 7.67 (1 H, d, J = 8.0 Hz). ¹³C NMR (100 MHz, DMSO): δ = 14.4 (q), 38.8 (t), 45.9 (t), 57.5 (d), 106.6 (d), 109.9 (d), 116.6 (d), 121.1 (d), 122.6 (s), 123.2 (d), 125.0 (d), 128.0 (s), 129.6 (s), 136.8 (s), 169.7 (s). MS: m/z 238 [M⁺]. Anal. Calcd for C₁₅H₁₄N₂O: C, 75.61; H, 5.92; N, 11.76. Found: C, 75.79; H, 6.01; N, 11.92.