[4+2] Cycloaddition of Dimethyl 1,2,4,5-Tetrazine-3,6-dicarboxylate with EWG-Substituted Primary Ketene N,O-Acetals : Synthesis of Tetrafunctional Pyridazines and Pyrroles

Abstract

A series of EWG-substituted primary ketene N,O-acetals were reacted with tetrazine-3,6-dicarboxylate yielding, by [4+2] cycloaddition, tetrafunctionalized pyridazines, which possess an EWG group, a primary amino function and two ester moieties. Reductive ring contraction of pyridazines gave aminopyrrole derivatives. Treatment of cyanamide with tetrazine-3,6-dicarboxylate led to a 5-amino-1,2,4-triazine derivative, which was rearranged to 4-aminoimidazole-2,5-dicarboxylic acid dimethyl ester.

Key words

Diels-Alder reaction - inverse electron demand - N,O-acetals - heterocycles - ring contraction

References

• 1 Troschütz R. Dennstedt T. Arch. Pharm. (Weinheim, Ger.)  1994,  327:  33 
• 2 Troschütz R. Lückel A. Arch. Pharm. (Weinheim, Ger.)  1992,  325:  785 
• 3 Landwehr J. Troschütz R. Synthesis  2005,  2414 
• 4 Boger DL. Weinreb S. Hetero Diels-Alder Methodology in Organic Synthesis   Academic Press; San Diego: 1987.  p.323 
• 5a Steglich W. Jeschke R. Buschmann E. Gazz. Chim. Ital.  1986,  116:  361 
• 5b Boger DL. Wyrocki RJ. J. Org. Chem.  1989,  54:  714 
• 6 Burg B. Dittmar W. Reni H. Steigel A. Sauer J. Tetrahedron Lett.  1975,  2897 
• 7 Neunhoefer H. Frühauf H.-W. Liebigs Ann. Chem.  1972,  758:  120 
• 8a Boger DL. Colemann RS. Panek JS. Huber FX. Sauer J. J. Org. Chem.  1985,  50:  5377 
• 8b Boger DL. Panek JS. Patel M. Org. Synth.  1992,  70:  79 
• 9 Muller J.-C. Ramuz H. Helv. Chim. Acta  1983,  66:  809 
• 10 Dornow A. Neuse E. Arch. Pharm. (Weinheim, Ger.)  1955,  288:  174 
• 11 Troschütz R. Grün L. Arch. Pharm. (Weinheim, Ger.)  1994,  327:  225 
• 12 Hojo M. Synthesis  1990,  195 
• 13 Keir WF. MacLennan A. J. Chem. Soc., Perkin Trans. 1  1977,  1321 
• 14 Boger DL. Kochanny MJ. J. Org. Chem.  1994,  59:  4950 
• 15a Bach NJ. Kornfeld EC. Jones ND. Chaneg MO. Dorman DE. Paschal JW. Clemens JA. Smalstig EB. J. Med. Chem.  1980,  23:  481 
• 15b Boger DL. Coleman RS. Panek JS. Yohannes D. J. Org. Chem.  1984,  49:  4405 
• 15c Boger DL. Soenen DR. Boyce CW. Hedrick MP. Jin Q. J. Org. Chem.  2000,  65:  2483 
• 16 Seitz G. Overheu W. Chem.-Ztg.  1979,  103:  6 
• 17 Nagy J. Ropp R. Alexovics M. Döpp D. Nyitrai J. Zahorszky N. Röttle H. J. Chem. Soc., Perkin Trans. 1  1993,  661 
• 18 Shriner R. Org. React.  1942,  1:  16