A Novel One-Pot, Three-Component Access to Hexahydropyrrolo[2,1-a]isoquinolines by an Alkylation-Dehydrohalogenation-1,3-Dipolar Cycloaddition Sequence

Miklós Nyerges; Barbara Somfai; Judit Tóth; László Tőke; András Dancsó; Gábor Blaskó

doi:10.1055/s-2005-869908

PAPER

A Novel One-Pot, Three-Component Access to Hexahydropyrrolo[2,1-a]isoquinolines by an Alkylation-Dehydrohalogenation-1,3-Dipolar Cycloaddition Sequence

Miklós Nyerges*^a, Barbara Somfai^a, Judit Tóth^a, László Tőke^a, András Dancsó^b, Gábor Blaskó^b
^a Organic Chemical Technology Research Group of the Hungarian Academy of Sciences, Budapest University of Technology and Economics, 1521 Budapest P.O. Box 91, Hungary
Fax: +361(463)3648; e-Mail: mnyerges@mail.bme.hu;
^b EGIS Pharmaceuticals Ltd., 1475 Budapest P.O. Box 100, Hungary

Abstract

All articles of this category

Abstract

A simple one-pot process for the alkylation of isoquinolines followed by a dehydrohalogenation of the quaternary salts formed and by an in situ trapping of azomethine ylides with appropriate dipolarophiles is described. This method has successfully been applied to the synthesis of benz[5,6]azepino[2,1-a]isoquinolines and 5,6-dihydroindazolo[3,2-a]isoquinoline 8-oxides via an 1,7-electrocyclization process of similar type azomethine ylides.

Key words

cycloadditions - electrocyclic reactions - heterocycles - tandem reactions - ylides

Full Text

References

1 Tsuge O. Kanemasa S. Adv. Heterocycl. Chem. 1989, 45: 232

For excellent reviews on 1,5-dipolar cyclizations, see:

2a Taylor EC. Turchi IJ. Chem. Rev. 1979, 79: 181

2b Huisgen R. Angew. Chem., Int. Ed. Engl. 1980, 19: 947

2c Bakulev VA. Kappe CO. Padwa A. In Organic Synthesis: Theory and Applications Vol. 3: Hudlicky T. JAI Press; Greenwich: 1996. p.149-229

3 Groundwater PW. Nyerges M. Adv. Heterocycl. Chem. 1999, 73: 97

4 Sliva W. Curr. Org. Chem. 2003, 7: 995

5a Jones RF. Howard KJ. Nichols JR. Snaith JS. J. Chem. Soc., Perkin Trans. 1 1998, 2061

5b Jones RF. Howard KJ. Snaith JS. Tetrahedron Lett. 1996, 37: 1707

6a Mangalagiu GC. Mangalagiu II. Olariu RI. Petrovanu M. Synthesis 2000, 2047

6b Mangalagiu I. Druta I. Constantinescu M. Humelnicu I. Petrovanu M. Tetrahedron 1996, 52: 8853

7 Potacek M. Topinka T. Dostal J. Marek J. Collect. Czech. Chem. Commun. 1994, 59: 2641

8 Tsuge O. Kanemasa S. Sakamoto K. Takenaka S. Bull. Chem. Soc. Jpn. 1988, 61: 2513

9 Minguez JM. Vaquero JJ. Alvarez-Builla J. Castano O. J. Org. Chem. 1999, 64: 7788

10 Zhou J. Zhang L. Hu Y. Hu H. J. Chem. Res., Synop. 1999, 552

11a Zhang L. Liang F. Sun L. Hu Y. Hu H. Synthesis 2000, 1733

11b Miki Y. Nakamura N. Yamakawa Y. Hachike H. Matsushita K. Heterocycles 2000, 53: 2143

11c Sliwa W. Heterocycles 1996, 43: 2005

12a Goff DA. Tetrahedron Lett. 1999, 40: 8741

12b Brooking P. Crawshaw M. Hird NW. Jones C. MacLachlan WS. Readshaw SA. Wilding S. Synthesis 1999, 1986

13a Bende Z. Simon K. Tóth G. Tőke L. Weber L. Liebigs Ann. Chem. 1982, 924

13b Bende Z. Bitter I. Tőke L. Weber L. Tóth G. Janke F. Liebigs Ann. Chem. 1982, 2146

13c Bende Z. Tőke L. Weber L. Tóth G. Janke F. Csonka G. Tetrahedron 1983, 40: 369

13d Tóth G. Tischner T. Bende Z. Szejtli G. Tőke L. Monatsh. Chem. 1990, 121: 529

13e Tischer T. Tőke L. Tóth G. Acta Chim. Hung. 1990, 127: 171

13f Janke F. Himmelreich U. Tóth G. Tischer T. Bende Z. Tőke L. J. Heterocycl. Chem. 1991, 28: 867

14 Fejes I. Nyerges M. Tőke L. Pak CS. Tetrahedron 2000, 56: 639

15 Nyerges M. Virányi A. Pintér . Tőke L. Tetrahedron Lett. 2003, 44: 793

16a Nyerges M. Fejes I. Virányi A. Groundwater PW. Tőke L. Tetrahedron Lett. 2001, 42: 5081

16b Nyerges M. Virányi A. Zhang W. Groundwater PW. Blaskó G. Tőke L. Tetrahedron 2004, 60: 9937

17a Anderson WK. Heider AR. Raju N. Yucht JA. J. Med. Chem. 1998, 31: 2097

17b Kuo R.-Y. Wu C.-C. Chang F.-R. Yeh J.-L. Chen I.-J. Wu I.-C. Bioorg. Med. Chem. Lett. 2003, 13: 821

17c McComsey DF. Maryanoff BE. J. Org. Chem. 2000, 65: 4938

18a Ahmad VU. Rahman A. Rasheed T. Rehman H. Heterocycles 1987, 26: 1251

18b Padwa A. Danca MD. Org. Lett. 2002, 4: 715

18c Gill CD. Greenhalgh DA. Simpkins NS. Tetrahedron 2003, 59: 9213

19a Andersen RJ. Faulkner DJ. Cun-heng H. Duyne GD. Clardy J. J. Am. Chem. Soc. 1985, 10: 5492

19b Gupton JT. Clough SC. Miller RB. Lukens JR. Henry CA. Kanters RPF. Sikorski JA. Tetrahedron 2004, 59: 207

19c Cironi P. Cuevas C. Albericio F. Alvarez MA. Tetrahedron 2004, 60: 8669

20 Cortes C. Romere EC. Ramirez GF. J. Heterocycl. Chem. 1994, 31: 1425