Atropodiastereoselective 5 N -Acylation of 1,5-Benzodiazepin-2-ones with ( S )-2-Phenylpropanoyl and ( S )-2-Phenylbutanoyl Chlorides.

5 N -Acylation of 1 N -methyl-1,5-benzodiazepin-2-ones with ( S )-2-phenylpropanoyl and ( S )-2-phenylbutanoyl chlorides afforded the (a 1 S ,a 2 S , S )-atropisomer ( I ) diastereoselectively over the (a 1 R ,a 2 R , S )-isomer ( II ) in the ratio of 1:0.06-0.15. The preferential formation of I may be explained by the thermodynamically preferable π-π stacking interaction between two benzene rings in the benzodiazepine ring and the acyl chloride during the reaction. Analysis using ab initio calculations (RI-MP2/6-31+G(d) level of theory) for the acylation reaction indicated the π-π stacking interaction in the transition state. Furthermore, isomer I was shown to be thermodynamically more stable than II . The higher stability of I may be caused by the folded form of the two benzene rings, which was revealed by NMR, X-ray, and computational analyses.