Syntheses of Tetrahydrobenzodiazepines via SN2-Type Ring-Opening of Activated Aziridines with 2-Bromobenzylamine Followed by Copper-Powder-Mediated C-N Bond Formation

A synthetic route to 2,3,4,5-tetrahydrobenzodiazepines has been devised through an S(N)2-type ring-opening of N-activated aziridines with 2-bromobenzylamine followed by an intramolecular cyclization through Cu-powder-mediated C-N bond formation. This operationally simple and extremely stereospecific ring-opening-cyclization approach is very efficient for the synthesis of a diverse array of the desired benzodiazepine derivatives in excellent yields of up to 94% and enantiomeric excess of up to >99%.