RSS-Feed abonnieren
DOI: 10.1055/s-0030-1259954
Copper(II)-Catalyzed Synthesis of Pyrimidines from Propargylic Alcohols and Amidine: A Propargylation-Cyclization-Oxidation Tandem Reaction
Publikationsverlauf
Publikationsdatum:
18. April 2011 (online)
![](https://www.thieme-connect.de/media/synlett/201108/lookinside/thumbnails/10.1055-s-0030-1259954-1.jpg)
Abstract
A new approach to the tandem synthesis of 2,4-disubstituted or 2,4,6-trisubstituted pyrimidines from propargylic alcohols with amidine is described. This reaction is catalyzed by 20 mol% Cu(OTf)2 to give pyrimidines in moderate to good yields via a propargylation-cyclization-oxidation tandem sequence.
Key words
pyrimidine - propargylation - amidine - copper - annulation
- Supporting Information for this article is available online:
- Supporting Information
- For representative examples of the application of pyrimidines, see:
-
1a
Lin Y.-L.Huang R.-L.Chang C.-M.Kuo Y.-H. J. Nat. Prod. 1997, 60: 982 -
1b
Gerlinck RGS.Braekman JC.Daloze D.Bruno I.Riccio R.Rogeau D.Amade P. J. Nat. Prod. 1992, 55: 528 -
1c
Traxler P.Bold G.Buchdunger E.Caravatti G.Furet P.Manley P.O’Reilly T.Wood J.Zimmermann J. Med. Res. Rev. 2001, 21: 499 -
1d
Zimmermann J.Buchdunger E.Mett H.Meyer T.Lydon NB. Bioorg. Med. Chem. Lett. 1997, 7: 187 -
1e
Hend NH.Hebat-Allah SA.Abdel-Rahman BA. Acta Pharm. 2008, 58: 359 -
1f
Dupin JP.Gryglewski RJ.Gravier D.Hou G.Casadebaig F.Swies J.Chlopicki S. J. Physiol. Pharmacol. 2002, 53: 625 -
1g
Nada MA.Hamdi MH.Nadia GK.Omar AM. Molecules 2008, 13: 1501 - For representative examples, see:
-
2a
Vicario J.Aparicio D.Palacios F. J. Org. Chem. 2009, 74: 452 -
2b
Robin A.Julienne K.Meslin JC.Deniaud D. Eur. J. Org. Chem. 2006, 634 -
2c
Sakai N.Aoki Y.Sasada T.Konakahara T. Org. Lett. 2005, 7: 4705 -
2d
Guzmán A.Romero M.Talamás FX. J. Org. Chem. 1996, 61: 2470 -
2e
Martinez AG.Fernández AH.Alvarez RM.Vilchez MDM.Gutierrez MLL.Subramanian LR. Tetrahedron 1999, 55: 4825 -
2f
Krechl J.Perez MA.Cuadrado FJ.Soto JL. Synthesis 1988, 122 -
2g
Ghosez L.Jnoff E.Bayard P.Sainte F.Beaudegnies R. Tetrahedron 1999, 55: 3387 -
2h
Movassaghi M.Hill MD. J. Am. Chem. Soc. 2006, 128: 14254 -
2i
Baxendale IR.Ley SV. J. Comb. Chem. 2005, 7: 483 -
2j
Kakiya H.Yagi K.Shinokubo H.Oshima K. J. Am. Chem. Soc. 2002, 124: 9032 -
2k
Blangetti M.Deagostino A.Prandi C.Zavattaro C.Venturello P. Chem. Commun. 2008, 1689 - For reviews, see:
-
3a
Joule JA.Mills K. In Heterocyclic Chemistry 4th ed.: Blackwell Science; London: 2000. p.194-215 -
3b
Bansal Raj K. In Heterocyclic Chemistry 4th ed.: New Age; New Delhi: 2007. p.514-560 -
3c
Rewcastle GW. In Comprehensive Heterocyclic Chemistry III Vol. 8:Katritzky AR.Aitken RA. Elsevier; Oxford: 2008. Chap. 8.02. p.191-203 -
3d
Rewcastle GW. In Comprehensive Heterocyclic Chemistry III Vol. 8:Katritzky AR.Aitken RA. Elsevier; Oxford: 2008. Chap. 8.02. p.235-245 -
3e
Hill MD.Movassaghi M. Chem. Eur. J. 2008, 14: 6836 -
3f
Simon C.Constantieux T.Rodriguez J. Eur. J. Org. Chem. 2004, 4957 - For selected examples, see:
-
4a
Palanki MS.Erdman PE.Gayo-Fung LM.Shevlin GI.Sullivan RW.Goldman ME.Ransone LJ.Bennett BL.Manning AM.Suto MJ. J. Med. Chem. 2000, 43: 3995 -
4b
Kiselyov AS. Tetrahedron Lett. 2005, 46: 1663 -
4c
Bagley MC.Brace C.Dale JW.Ohnesorge M.Phillips NG.Xiong X.Bower J. J. Chem. Soc., Perkin Trans. 1. 2002, 1663 -
4d
Rossi E.Abbiati G.Pini E. Synlett 1999, 1265 -
5a
Müller TJJ.Braun R.Ansorge M. Org. Lett. 2000, 2: 1967 -
5b
Bagley MC.Hughes DD.Lubinu MC.Merritt EA.Taylor PH.Tomkinson NC. QSAR Comb. Sci. 2004, 23: 859 -
5c
Bagley MC.Hughes DD.Taylor PH. Synlett 2003, 259 -
5d
Bannwarth P.Valleix A.Grée D.Grée R. J. Org. Chem. 2009, 74: 4646 -
5e
Adamo MFA.Adlington RM.Baldwin JE.Pritchard GJ.Rathmell RE. Tetrahedron 2003, 59: 2197 -
5f
Baldwin JE.Pritchard GJ.Rathmell RE.
J. Chem. Soc., Perkin Trans. 1 2001, 2906 -
5g
Adlington RM.Baldwin JE.Catterick D.Pritchard G. J. Chem. Soc., Perkin Trans. 1 1999, 855 -
5h
Karpov AS.Müller TJJ. Synthesis 2003, 2815 -
5i
Karpov AS.Müller TJJ. Org. Lett. 2003, 5: 3451 -
5j
Bagley MC.Hughes DD.Sabo HM.Taylor PH.Xiong X. Synlett 2003, 1443 -
5k
Bagley MC.Lin Z.Pope SJA. Tetrahedron Lett. 2009, 50: 6818 -
5l
Taylor RJK.Reid M.Foot J.Raw SA. Acc. Chem. Res. 2005, 38: 851 -
6a
Hao L.Pan Y.Wang T.Lin M.Chen L.Zhan Z. Adv. Synth. Catal. 2010, 352: 3215 -
6b
Wang T.Ma R.Liu L.Zhan Z. Green Chem. 2010, 12: 1576 -
6c
Pan Y.Zheng F.Lin H.Zhan Z. J. Org. Chem. 2009, 74: 3148 -
6d
Liu X.Huang L.Zheng F.Zhan Z. Adv. Synth. Catal. 2008, 350: 2778 -
6e
Zhan Z.Cai X.Wang S.Yu J.Liu H.Cui Y. J. Org. Chem. 2007, 72: 9838 -
6f
Zhan Z.Yu J.Liu H.Cui Y.Yang R.Yang W.Li J. J. Org. Chem. 2006, 71: 8298
References and Notes
General Procedure
for the Synthesis of Substituted Pyrimidines
To a
solution of propargylic alcohol 1 (0.5
mmol) and amidine 2 (1 mmol) in PhCl (2
mL), Cu(OTf)2 (0.1 mmol) was added, and it was stirred
at reflux. When the reaction was completed (monitored by TLC), the
solvent was removed under vacuum, and then the residue was further purified
by silica gel column chromatography (PE and EtOAc) to afford pyrimidine.