Synthesis and stereochemical characterization of 1,2,7,11b- tetrahydropyrrolo[1,2-d][1,4]benzodiazepine-3,6(5H)-diones, obtained via Raney nickel hydrogenation of tetrahydroisoxazolo[2,3-d][1,4]benzodiazepinones

Abstract

Catalytic hydrogenation (Raney nickel) of 2-alkoxycarbonyl-1,2,7,11b-tetrahydroisoxazolo [2,3,-d][1,4]-benzodiazepin-6(5H)-ones (1)produces 1,2,7,11b-tetrahydro-2-hydroxypyrrolo[1,2-d][1,4]benzodi-azepine-3,6(5H)-diones (2a–c). Their stereochemical characterization has been accomplished by ¹H n.m.r. spectroscopy, principally by computer simulation of the lanthanoid-induced shift of the proton resonances. The result show that some 10-chloro-1,2,7,11b-tetrahydro-2-hydroxy-7-methyl-11b-phenylpyrrolo[1,2-d][1,4]benzodiazepine-3,6(5H)-diones exits predominantly in the transoid conformation in chloroform solution at room temperature; a related 7-unsubstituted product shows rapid conformational equilibration in comparison with the n.m.r. time scale, characterized by a slight conformational bias to the cisoid form.