Stereoselective in‐vitro aromatic‐ring oxygenations of chiral 1,4‐benzodiazepin‐2‐ones

Biological N(1)‐demethylation and C(3)‐hydroxylation of two enantiomeric 1,4‐benzodiazepin‐2‐ones 1 and 2 (cf. scheme 2 ) were found to be nonstereoselective. Aromatic‐ring hydroxylation, however, took place in the ( S )‐series only, leading to 3′‐ and 4′‐hydroxylated, N(1)‐demethylated, metabolites ( 54 and 56 , cf. scheme 5 : these structures were unambiguously confirmed by comparing their UV., CD., and mass spectra with those of authentic specimens). Several compounds, theoretically conceivable as products of hydroxylation in the aromatic A‐ring of 1 and 2 by mechanisms including the NIH‐shift (cf. scheme 3 ), were synthesized but none of these compounds was yet isolated from in vitro incubation mixtures.