title: Electrophilic-induced cyclization reaction of hexahydroindolinone derivatives and its application toward the synthesis of (+/-)-erysotramidine.
abstract: 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.
authors.affiliation: Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA. chemap@emory.edu
authors.forename: Albert
authors.initials: A
authors.lastname: Padwa
authors.forename: Hyoung Ik
authors.initials: HI
authors.lastname: Lee
authors.forename: Paitoon
authors.initials: P
authors.lastname: Rashatasakhon
authors.forename: Mickea
authors.initials: M
authors.lastname: Rose
mesh_terms: D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D007769:Lactams; C492626:erysotramidine; C429964:hexahydroindolinone