Sequential Hydration-Condensation-Double Cyclization of Pyridine-Substituted 2-Alkynylanilines: An Efficient Approach to Quinoline-Based Heterocycles

Abstract

An environmentally benign and atom-economical process to construct a unique quinoline-based tetracyclic scaffold, through sequential hydration-condensation-double cyclization reactions, has been described. The reaction starts with readily available pyridine-substituted o-alkynylanilines and β-keto esters, promoted by p-toluenesulfonic acid in ethanol in one pot. In the absence of β-keto esters, multisubstituted quinolines are formed bimolecularly in reasonable yields.

Key words

alkynes - cyclization - heterocycles - quinoline - tandem reaction

References

• 1 Hintermann L. Labonne A. Synthesis  2007,  1121 
• 2a Meseguer B. Alonso-Díaz D. Griebenow N. Herget T. Waldmann H. Angew. Chem. Int. Ed.  1999,  38:  2902 
• 2b Duclos S. Stoeckli-Evans H. Ward TR. Helv. Chim. Acta  2001,  84:  3148 
• 2c Menashe N. Reshef D. Shvo Y. J. Org. Chem.  1991,  56:  2912 
• 2d Menashe N. Shvo Y.
  J. Org. Chem.  1993,  58:  7434 
• 2e Xu G. Hartman TL. Wargo H. Turpin JA. Buckheit RW. Cushman M. Bioorg. Med. Chem.  2002,  10:  283 
• 2f Olivi N. Thomas E. Peyrat J. Alami M. Brion J. Synlett  2004,  2175 
• 3a Chapdelaine MJ. Warwick PJ. Shaw A. J. Org. Chem.  1989,  54:  1218 
• 3b Kawato HC. Nakayama K. Inagaki H. Ohta T. Org. Lett.  2001,  3:  3451 
• 4a Kouznetsov VV. Vargas Méndez LY. Meléndez Gómez CM. Curr. Org. Chem.  2005,  9:  141 
• 4b Madapa S. Tusi Z. Batra S. Curr. Org. Chem.  2008,  12:  1116 
• 5a Wang Y. Peng C. Liu L. Zhao J. Su L. Zhu Q. Tetrahedron Lett.  2009,  50:  2261 
• 5b Liu L. Wang Y. Wang H. Peng C. Zhao J. Zhu Q. Tetrahedron Lett.  2009,  50:  6715 
• 5c Wang H. Liu L. Wang Y. Peng C. Zhang J. Zhu Q. Tetrahedron Lett.  2009,  50:  6841 
• 5d Zhao J. Peng C. Liu L. Wang Y. Zhu Q. J. Org. Chem.  2010,  75:  7504 
• 6 Peng C. Wang Y. Liu L. Wang H. Zhao J. Zhu Q. Eur. J. Org. Chem.  2010,  818 
• 7 Yotphan S. Bergman RG. Ellman JA. Org. Lett.  2010,  12:  2978 ; and references cited therein
• 8a Joshi AA. Viswanathan CL. Bioorg. Med. Chem. Lett.  2006,  16:  2613 
• 8b Sadana AK. Mirza Y. Aneja KR. Prakash O. Eur. J. Med. Chem.  2003,  38:  533 
• 8c Kym PR. Kort ME. Coghlan MJ. Moore JL. Tang R. Ratajczyk JD. Larson DP. Elmore SW. Pratt JK. Stashko MA. Falls HD. Lin CW. Nakane M. Miller L. Tyree CM. Miner JN. Jacobson PB. Wilcox DM. Nguyen P. Lane BC. J. Med. Chem.  2003,  46:  1016 
• 8d Nayyar A. Jain R. Curr. Med. Chem.  2005,  12:  1873