The synthesis of cyclo(amide-ester)s based on #alpha#-amino acids and #epsilon#-aminocaproic acid in combination with #beta#-hydroxy acids was achieved by ring-expansion reactions. Three different approaches were followed: (i) According to Shemyakin, #epsilon#-caprolactam or diketopiperazines were acylated with differently substituted #beta#-benzyloxyacyl chlorides. Removal of the protecting group by hydrogenolysis over a palladium catalyst results in hydroxyacyl incorporation into the #epsilon#-caprolactam or the diketopiperazine ring and formation of the eleven-membered cyclo(amide-ester)s 1a-c or the fourteen-membered cyclo(diamide-diester)s 2a-c. (ii) Alternatively, the cyclo(amide-ester)s 1a-c were obtained via intramolecular nucleophilic substitution of the halogen atom in N-(3-halogenoacyl)-#epsilon#-caprolactam by the oxygen atom of the lactam unit followed by reaction with water. (iii) Finally, results on the intramolecular Michael addition in N-(acryloyl)- and N-(crotonyl)-#epsilon#-caprolactams are presented. The Michael addition was induced by the nuclephilic addition of the lactam oxygen atom to the CC double bond followed by a sequence of reactions, which leads to the cyclo(amide-ester)s 1a, b.
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