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Synthesis of and Tautomerism in 3-Acyltetramic Acids

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journal contribution
posted on 04.03.2011, 00:00 by Yong-Chul Jeong, Mark G. Moloney
The synthesis of 3-acyltetramic acids, the substructure of bioactive natural products, via O-acylation of tetramic acids with carboxylic acids followed by acyl migration, has been investigated. This acylation sequence is mediated by N,N′-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) and is very sensitive to the nature of the nitrogen substituent (R1), the nature of the carboxylic acid (R2CO2H), and the amount of DMAP. Acylation of N-acyl tetramic acids with an alkyl carboxylic acid using 1.3 equiv of DMAP (with 1.1 equiv of DCC) unexpectedly gave the 3-acyltetramic acid directly as a result of acyl migration induced by excess amounts of DMAP. On the other hand, N-unsubstituted, N-alkyl, and N-acyl tetramic acids with alkyl and aromatic carboxylic acids gave the O-acyl tetramic acids by using only 0.1 equiv of DMAP (with 1.1 equiv of DCC); these could be further rearranged to the acyl product by treatment with excess DMAP. The tautomeric equilibrium of these 3-acyltetramic acids in solution was found to strongly depend on the nitrogen substituent group (R1) rather than the 3-acyl group.