Palladium-catalysed synthesis of enantiopure 1,2,4,5-tetrahydro-1,4-benzodiazepin-3-(3H)-one derivatives

A convenient procedure for the preparation of 1,2,4,5-tetrahydro-1,4-benzodiazepin-3-(3H)-one derivatives (S)-2 from chiral a-substituted N-n-butyl-N-(o-iodobenzyl)glycinamides (S)-1 has been developed. Seven-membered ring formation occurs through an intramolecular N-arylation catalysed by palladium and bis(phosphine) ligands. The use of chelating bis(phosphines) allows to minimize or entirely suppress carbon-2 racemisation which occurs when a mono(phosphine) ligand is used.