An approach toward isoindolobenzazepines using the ammonium ylide/Stevens [1,2]-rearrangement sequence

Ammonium ylides derived from the Cu(II)-catalyzed decomposition of a-diazo carbonyls tethered to tertiary amines underwent a benzylic Stevens [1,2]-re arrangement to give tetrahydroisoquinolines or benzazepines containing fuse d five-membered rings, a feature found in the cephalotaxus alkaloids. Model studies were also carried out toward the synthesis of lennoxamine, a membe r of the isoindolobenzazepine family of alkaloids. The approach utilized is based on the Rh(II)-catalyzed reaction of an a-diazo carbonyl compound con taining an amido group in the gamma -position. Treatment of several N,N-dia lkyl-substituted amido diazo-esters with Rh-2(OAc)(4) in benzene at 80 degr eesC in the presence of several dienophiles gave [4 + 2]-cycloadducts deriv ed from the Diels-Alder reaction of a transient a-amino isobenzofuran inter mediate. In the absence of an external trapping agent, no rearranged produc t derived from an ammonium ylide intermediate could be detected in the crud e reaction mixture. In contrast to this result, reaction of the related dia zo dihydroisoquinoline amide 46 with Rh-2(OAc)(4) afforded the isoindoloben zazepine ring system in high yield. Formation of the 5,7-fused skeleton was rationalized in terms of a spirocyclic ammonium ylide that underwent a pre ferential Stevens [1,2]-shift of the benzylic carbon atom. While we were ul timately thwarted in using the ammonium ylide/rearrangement cascade for a l ennoxamine synthesis by an uncooperative diazo transfer reaction, the casca de sequence was shown to be useful for the preparation of various isoindolo benzazepines.