A Catalyst-Free MCR Approach to 1,5-Benzodiazepines

Significance

Reported is the stereoselective synthesis of cis-2,3-dihydro-4-perfluoroalkyl-1H-1,5-benzodiazepines 4 via a catalyst-free three-component reaction. Both aliphatic and aromatic aldehydes participate efficiently in the reaction. In general, benzaldehydes bearing EDGs in the para-position gave superior yields of products. Heteroaromatic aldehydes were also competent reaction partners. The cis relationship of the CO₂Me and R^² groups was proved on the basis of ^¹H NMR coupling constants and by X-ray crystallographic analysis. A plausible reaction mechanism as shown is proposed based on previous ­related reports.