Thieme Gruppe, Synthesis: Journal of Synthetic Organic Chemistry, 06(2010), p. 933-942, 2010
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A number of Nα-alkyl,Nβ-acylhydrazines have been synthesized via the Ugi reaction of N-acylhydrazones with an isocyanide and trifluoroacetic acid. The trifluoroacetic acid acted as a ‘silent partner' and becomes removed upon basic workup of the reaction. These compounds have been efficiently modified further via reductive alkylation to produce Nα,Nα-dialkyl,Nβ-acylhydrazines. The two groups of novel hydrazinopeptide motifs have been shown by simple ¹H NMR spectroscopic experiments to display two different secondary structure patterns. These observations were confirmed by X-ray crystallographic analysis. Combining the hydrazone and carboxylic acid moieties in one reaction precursor offers the opportunity for an ‘intramolecular' hydrazino-Ugi reaction, which was also demonstrated.