Pictet-Spengler Synthesis of Naphthoquino[b]-benzo[e][1,4]diazepines

Significance

The paper describes the synthesis of a variety of dihydro-1H-1,4-naphthoquino[b]-benzo[e][1,4]diazepines by the Pictet-Spengler reaction of readily accessible 2,3-diamino-1,4-naphthoquinones with aldehydes. On the basis of the normal mechanism of the Pictet-Spengler reaction, two products are expected due to the formation of two different iminium salts. However, the regioselectivity is dictated by the presence of R¹ and R² as EWGs. Furthermore, substitution ortho to the cyclization site prevents reaction by presumed steric hindrance, and bulky aldehydes also give low yield of products due to steric effects. The scope of the reaction was reasonably tested.