A study of vinyl radical cyclization using N-alkenyl-7-bromo-substituted hexahydroindolinones.
A new method for the synthesis of the octahydropyrrolo[3,2,1-ij]quinoline ring system that possesses the characteristic skeleton of the aspidosperma family of alkaloids has been developed. The method utilizes an intramolecular Diels-Alder reaction of an amido-substituted furan across a tethered indole pi-bond. To apply this strategy to the synthesis of the indole alkaloid spegazzinidine, it was necessary to address the problem of assembling the final D-ring of the pentacyclic skeleton. Radical cyclization of a model N-allyl-7-bromo-3a-methylhexahydroindolinone system was found to preferentially lead to the 6-endo-trig cyclization product, with the best yield being obtained under high dilution conditions. The six-membered cyclized product is generated through two reaction pathways: (a) 6-endo-trig ring closure and (b) rearrangement of an intermediate methylene-cyclopentyl radical obtained by 5-exo-trig cyclization. A number of related 7-bromo-substituted hexahydroindolinones containing tethered olefinic groups were prepared and found to undergo efficient cyclization under both radical and palladium-mediated reaction conditions. Vinyl radical cyclization with several N-butenyl-substituted systems afforded a mixture of 6-exo and 7-endo cyclization products. A protocol to introduce an ethyl substituent into the C20-position of the aspidospermidine skeleton was also developed.
Padwa
Albert
A
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA. chemap@emory.edu
Rashatasakhon
Paitoon
P
Ozdemir
Ayse Daut
AD
Willis
Jerremey
J
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry
D000470:Alkaloids; D005609:Free Radicals; D007211:Indoles; C429964:hexahydroindolinone; D010165:Palladium