Enamines of 3-acyltetramic acids from β-enamino amides and amino acids

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

“…When the deprotection of 3 was performed in neat TFA for 5 min, the keto amides 5c–f were obtained in poor enantiomeric excess and the concomitantly formed pyrrolinones 6c–f were fully racemic. This again is in sharp contrast to analogues 9 , which cyclise to 10 with excellent retention of configuration [ 34 ].…”

“…For the purposes of this study we used two β-enamino amides 1 (R 1 = H, Ph), that are easily prepared in quantitative yields by condensation of Boc-monoprotected ethylenediamine with commercially available acetoacetamides. As a first step we acylated the starting compounds 1 with mixed carbonic anhydrides of N -protected amino acids, applying a procedure previously developed by us for closely related analogues [ 34 ] ( Scheme 1 ). Thus, the α-C-acylated intermediates 3a–j ( Table 1 ) and 4 ( Table 2 ) were obtained in good yields and excellent chiral integrity (er 3c – f ≥ 99:1).…”

“…Under identical conditions (neat TFA, rt) compounds 9 do not react even after 12 hours. A reaction occurs only upon heating in TFA solution, but then the cyclisation mode is completely different and leads to enaminotetramic derivatives 10 instead of pyrrolin-4-ones 6 [ 34 ]. Another drawback caused by the acidic deprotection conditions was the loss of chiral integrity.…”

2-Methyl-4-Oxo-4,5-Dihydro-1H-Pyrrole-3-Carboxylic Acid Phenylamide

“…In the course of our ongoing studies on a class of synthetic intermediates, obtained by the acylation of β-enamino amides with N-protected amino acids, we have observed two distinct modes of acid-catalyzed intramolecular cyclization in these compounds, leading to either enaminotetramic derivatives [18] or pyrrolin-4-ones [19]. Our experiments so far have focused on acid-stable protecting groups, which in both modes are retained in the final products, except for one unusual case of 2-nitrobenzoyl protection [20].…”

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

“…The scope of these reductive cyclizations is limited by the availability of the necessary intermediates and has remained largely underexplored, especially with regard to 4-quinolones with long-chain substituents at the C-2 position. As a way of expanding the scope of this methodology, we resorted to the α- C -acylation of β-enamino amides, a reliable reaction, the utility of which we have already demonstrated in other contexts [ 62 – 63 ].…”