Synthesis of pseudopeptidic ( S)-6-amino-5-oxo-1,4-diazepines and ( S)-3-benzyl-2-oxo-1,4-benzodiazepines by an Ugi 4CC Staudinger/aza-Wittig sequence

Abstract

Sequential Ugi reaction between p-substituted arylglyoxals, alkylamines, cyclohexyl isocyanide and 3-azido-( S)-2-( tert-butoxycarbonylamino)propanoic acid, followed by a Staudinger/aza-Wittig cyclization in the presence of triphenylphosphine, gave rise to enantiomerically pure N-cyclohexyl 4-alkyl-2-aryl-5-oxo-( S)-6-( tert-butoxycarbonylamino)-4,5,6,7-tetrahydro-1 H-1,4-diazepine-3-carboxamides, that can be useful for new drug design. By the same sequence, p-substituted benzaldehydes, 2-aminobenzophenone, cyclohexyl isocyanide and ( S)-3-phenyl-2-azidopropionic acid gave rise to N-cyclohexyl 2-(( S)-3-benzyl-2-oxo-5-phenyl-2,3-dihydro-1 H-benzo[ e][1,4]diazepin-1-yl)-( R/ S)-2-arylacetamides.