hexahydroindolinone and erysotramidine

A convenient synthesis of variously substituted octahydroindolo[7a,1a]-isoquinolinones has been achieved by an acid-induced cyclization of hexahydroindolinones bearing tethered phenethyl groups. The formation of a single lactam diastereomer is the result of the stereoelectronic preference for axial attack by the aromatic ring onto the initially formed N-acyliminium ion from the least hindered side. Additional experiments showed that a variety of hexahydroindolinones containing tethered pi-bonds undergo a related acid-induced cyclization reaction. Treatment of the 3-methylbut-3-enyl-substituted hexahydroindolinone with acid furnished a 3:1 mixture of isomeric octahydropyrido[2,1-i]indolinones in near-quantitative yield. Interestingly, cyclization of the closely related 1-(3-methoxybut-3-enyl)-substituted hexahydroindolin-one afforded a pyrrolo[3,2,1-ij]quinolinone as the exclusive product. With this system, initial protonation takes place on the more nucleophilic enol ether pi-bond and the resulting carbonium ion undergoes a subsequent cyclization with the enamido pi-bond to give the observed product. The electrophilic promoted cyclizations were extended to include the related hexahydro[1]pyrindinone and 1H-quinolinone systems. An NBS-promoted intramolecular electrophilic aromatic substitution reaction of 1-[2-(3,4-dimethoxyphenyl)ethyl]-1,4,5,6-tetrahydroindolinone was used to assemble the tetracyclic core of the erythrinone skeleton. The resulting cyclized product was transformed into (+/-)-erysotramidine in three additional steps.

Topics: Cyclization; Heterocyclic Compounds, 4 or More Rings; Indoles; Lactams; Molecular Structure; Stereoisomerism