A Route to Alkenyl-Substituted
4-Hydroxypyridine and Pyrimidine Derivatives via Three-Component
Access to β-Alkoxy-β-ketoenamides

Mrinal K. Bera; Hans-Ulrich Reissig

doi:10.1055/s-0029-1218787

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-00000084.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synthesis 2010(13): 2129-2138
DOI: 10.1055/s-0029-1218787

PAPER

A Route to Alkenyl-Substituted 4-Hydroxypyridine and Pyrimidine Derivatives via Three-Component Access to β-Alkoxy-β-ketoenamides

Mrinal K. Bera, Hans-Ulrich Reissig*
Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Fax: +49(30)83855367; e-Mail: hans.reissig@chemie.fu-berlin.de;

Further Information

Publication History

Received 29 March 2010
Publication Date:
20 May 2010 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

β-Alkoxy-β-ketoenamides with an alkenylated side arm were prepared by three-component reaction of lithiated methoxyallene, nitriles, and α,β-unsaturated carboxylic acids. Their subsequent treatment with trimethylsilyl triflate and base provided 6-alkenyl-4-hydroxypyridine derivatives that were converted into the corresponding nonaflates. Alternatively, condensation of β-alkoxy-β-ketoenamides with an ammonium salt led to the smooth formation of alkenyl-substituted pyrimidine derivatives. The alkenyl group in pyridine or pyrimidine derivatives allows a wide scope of functional group modification. Moreover, the pyridin-4-yl nonaflates are excellent candidates for palladium-catalyzed coupling reactions and the 6-methyl group of the pyrimidine derivatives could also be employed for the introduction of functional groups and subsequent reactions. A variety of highly substituted pyridine and pyrimidine derivatives are available by this modular route to heterocycles.

Key words

alkoxyallenes - enamides - pyridines - nonaflates - pyrimidines - Suzuki couplings

References

1a Coutts RT. Casy FA. Chem. Heterocycl. Compd. (Engl. Transl.) 1975, 14: 445

Google Scholar
1b McInnes AG. Smith DG. Wright JLC. Vining LC. Can. J. Chem. 1977, 55: 4159

Google Scholar
1c Berthel SJ. Marks IM. Yin X. Mischke SG. Orzechowski L. Pezzoni G. Sala F. Vassilev LT. Anti-Cancer Drugs 2002, 13: 359

Google Scholar
1d Bringmann G. Reichert Y. Kane V. Tetrahedron 2004, 60: 3539

Google Scholar
1e Chinchilla R. Nájera C. Yus M. Chem. Rev. 2004, 104: 2667

Google Scholar
1f Schnermann MJ. Boger DL. J. Am. Chem. Soc. 2005, 127: 15704

Google Scholar
1g Whitson EL. Mala SMVD. Veltri CA. Bugni TS. de Silva ED. Ireland CM. J. Nat. Prod. 2006, 69: 1833

Google Scholar
1h Horiuch M. Murakami C. Fukamiya N. Yu D. Chen T.-S. Bastow KF. Zhang D.-C. Taishi Y. Imakura Y. Lee K.-H. J. Nat. Prod. 2006, 69: 1271

Google Scholar
1i Kariya Y. Kubota T. Fromont J. Kobayashi J. Tetrahedron Lett. 2006, 47: 997

Google Scholar
1j Nishi T. Kubota T. Fromont J. Sasaki T. Kobayashi J. Tetrahedron 2008, 64: 3127

Google Scholar
1k Aida W. Ohtsuki T. Li X. Ishibashi M. Tetrahedron 2009, 65: 369

Google Scholar
1l Hayashi A. Arai M. Fujita M. Kobayashi M. Biol. Pharm. Bull. 2009, 32: 1261

Google Scholar
2 Functional Organic Materials Müller TJJ. Bunz UHF. Wiley-VCH; Weinheim: 2007.

Google Scholar
3a Hofmeier H. Schubert US. Chem. Commun. 2005, 2423

Google Scholar
3b Schubert US. Eschbaumer C. Angew. Chem. Int. Ed. 2002, 41: 2892 ; Angew. Chem. 2002, 114, 3016

Google Scholar
3c Lehn J.-M. Supramolecular Chemistry-Concepts and Perspective Wiley-VCH; Weinheim: 1995.

Google Scholar
4a Karpov AS. Müller TJJ. Synthesis 2003, 2815

Google Scholar
4b Bevk D. Groselj U. Meden A. Svete J. Stanovnik B. Helv. Chim. Acta 2007, 90: 1737

Google Scholar
4c Sagar R. Kim M.-J. Park SB. Tetrahedron Lett. 2008, 49: 5080

Google Scholar
4d Xie F. Zhao H. Zhao L. Lou L. Hu L. Bioorg. Med. Chem. Lett. 2009, 19: 275

Google Scholar
For reviews, see:
5a Varela JA. Saá C. Chem. Rev. 2003, 103: 3787

Google Scholar
5b Henry GD. Tetrahedron 2004, 60: 6043

Google Scholar
5c Bagley MC. Glover C. Merritt EA. Synlett 2007, 2459

Google Scholar
For selected recent examples, see:
5d Movassaghi M. Hill MD. J. Am. Chem. Soc. 2006, 128: 4592

Google Scholar
5e Movassaghi M. Hill MD. Ahmad OK. J. Am. Chem. Soc. 2007, 129: 10096

Google Scholar
5f Lu J.-Y. Arndt H.-D. J. Org. Chem. 2007, 72: 4205

Google Scholar
5g Craig D. Paina F. Smith SC. Chem. Commun. 2008, 3408

Google Scholar
5h Manning JR. Davies HML. J. Am. Chem. Soc. 2008, 130: 8602

Google Scholar
5i Liu S. Liebeskind LS. J. Am. Chem. Soc. 2008, 130: 6918

Google Scholar
5j Barluenga J. Ángel M. Rodríguez F. García-García P. Aguilar E. J. Am. Chem. Soc. 2008, 130: 2764

Google Scholar
5k Donohoe TJ. Fishlock LP. Procopiou PA. Org. Lett. 2008, 10: 285

Google Scholar
For examples with alkenyl-substituted pyridine derivatives, see:
5l Beveridge RE. Arndtsen BA. Synthesis 2010, 1000

Google Scholar
6a Brown DJ. In Comprehensive Heterocyclic Chemistry Vol. 3: Katritzky AR. Rees CW. Pergamon; Oxford: 1984. Chap. 2.13.

Google Scholar
6b Eicher T. Hauptmann S. Chemie der Heterocyclen Thieme; Stuttgart: 1994. p.398

Google Scholar
6c Gilchrist TL. Heterocyclenchemie Neunhoeffer H. Wiley-VCH; Weinheim: 1995. p.270

Google Scholar
6d Hoffmann MG. In Houben-Weyl Vol. E9: Schaumann E. Thieme; Stuttgart: 1996.

Google Scholar
6e Von Angerer S. Science of Synthesis Vol. 16: Yamamoto Y. Thieme; Stuttgart: 2004. p.379

Google Scholar
6f Müller TJJ. Braun R. Ansorge M. Org. Lett. 2000, 2: 1967

Google Scholar
6g Sakai N. Aoki Y. Sasada T. Kanakahara T. Org. Lett. 2005, 7: 4705

Google Scholar
6h Movassaghi M. Hill HD. J. Am. Chem. Soc. 2006, 128: 14254

Google Scholar
7a Pinner A. Ber. Dtsch. Chem. Ges. 1890, 23: 2919

Google Scholar
7b Pinner A. Ber. Dtsch. Chem. Ges. 1892, 25: 1414

Google Scholar
7c Pinner A. Ber. Dtsch. Chem. Ges. 1895, 28: 483

Google Scholar
8a Biginelli P. Ber. Dtsch. Chem. Ges. 1891, 24: 1317

Google Scholar
8b Biginelli P. Ber. Dtsch. Chem. Ges. 1891, 24: 2962

Google Scholar
8c Biginelli P. Ber. Dtsch. Chem. Ges. 1893, 26: 447

Google Scholar
8d Kappe CO. J. Org. Chem. 1997, 62: 7203

Google Scholar
8e Kappe CO. Bioorg. Med. Chem. Lett. 2000, 10: 49

Google Scholar
Recent pyrimidine derivative syntheses starting from enamides:
9a Barthakur MG. Borthakur M. Devi P. Saikia CJ. Saikia A. Bora U. Chetia A. Boruah RC. Synlett 2007, 223

Google Scholar
9b Hill MD. Movassaghi M. Chem. Eur. J. 2008, 14: 6836

Google Scholar
For reviews on alkoxyallenes, see:
10a Zimmer R. Synthesis 1993, 165

Google Scholar
10b Zimmer R. Khan FA. J. Prakt. Chem. 1996, 338: 92

Google Scholar
10c Reissig H.-U. Hormuth S. Schade W. Okala Amombo MG. Watanabe T. Pulz R. Hausherr A. Zimmer R. J. Heterocycl. Chem. 2000, 37: 597

Google Scholar
10d Zimmer R. Reissig H.-U. In Modern Allene Chemistry Vol. 2: Krause N. Hashmi ASK. Wiley-VCH; Weinheim: 2004. p.425-492

Google Scholar
10e Reissig H.-U. Zimmer R. Science of Synthesis Vol. 44: Krause N. Thieme; Stuttgart: 2007. p.301-352

Google Scholar
10f Brasholz M. Reissig H.-U. Zimmer R. Acc. Chem. Res. 2009, 42: 45

Google Scholar
For selected recent applications developed by our group, see:
10g Al-Harrasi A. Reissig H.-U. Angew. Chem. Int. Ed. 2005, 44: 6227 ; Angew Chem. 2005, 117, 6383

Google Scholar
10h Kaden S. Reissig H.-U. Org. Lett. 2006, 8: 4763

Google Scholar
10i Sörgel S. Azap C. Reissig H.-U. Org. Lett. 2006, 8: 4875

Google Scholar
10j Brasholz M. Reissig H.-U. Angew. Chem. Int. Ed. 2007, 46: 1634 ; Angew. Chem. 2007, 119, 1659

Google Scholar
10k Gwiazda M. Reissig H.-U. Synthesis 2008, 990

Google Scholar
11a Flögel O. Dash J. Brüdgam I. Hartl H. Reissig H.-U. Chem. Eur. J. 2004, 10: 4283

Google Scholar
11b Flögel O, and Reissig H.-U. inventors; DE 10,336,497.
11c Dash J. Lechel T. Reissig H.-U. Org. Lett. 2007, 9: 5541

Google Scholar
11d Eidamshaus C. Reissig H.-U. Adv. Synth. Catal. 2009, 351: 1162

Google Scholar
11e Dash J. Reissig H.-U. Chem. Eur. J. 2009, 15: 6811

Google Scholar
11f Lechel T. Dash J. Hommes P. Lentz D. Reissig H.-U. J. Org. Chem. 2010, 75: 726

Google Scholar
11g Lechel T. Dash J. Eidamshaus C. Brüdgam I. Reissig H.-U. Org. Biomol. Chem. 2010, 7: DOI: 10.1039/B925468D

Google Scholar
12a Lechel T. Möhl S. Reissig H.-U. Synlett 2009, 1059

Google Scholar
12b Lechel T. Reissig H.-U. Eur. J. Org. Chem. 2010, 2555

Google Scholar
13 Lechel T. Dash J. Brüdgam I. Reissig H.-U. Eur. J. Org. Chem. 2008, 3647

Crossref Google Scholar
14a Miyaura N. Yamada K. Suzuki A. Tetrahedron Lett. 1979, 20: 3437

Google Scholar
14b Miyaura N. Suzuki A. J. Chem. Soc., Chem. Commun. 1979, 866

Google Scholar
14c Miyaura N. Suzuki A. Chem. Rev. 1995, 95: 2457

Google Scholar
15 Lindsay KB. Pyne SG. Aust. J. Chem. 2004, 57: 669

Crossref Google Scholar
16 Riley HL. Morley JF. Friend NAC. J. Chem. Soc. 1932, 1875

Crossref Google Scholar