Stereoselective tetrapyrido[2,1-a]isoindolone synthesis via carbanionic and radical intermediates: a model study for the Tacaman alkaloid D/E ring fusion.
Cyclization under both radical and carbanionic conditions of N-substituted 3-phenylsulfanylisoindolin-1-one 14 containing a chiral N-tether incorporating an enoate ester as the acceptor leads to tetrahydropyrido[2,1-a]isoindolones stereoselectively. The major product 17 from carbanionic cyclization was stereoselectively desulfurized with nickel boride allowing correlation of cyclization products from both methodologies. The cyclization stereoselectivities have been rationalised using a transition-state model in which the acceptor grouping adopts a pseudoaxial configuration. This contrasts with other 6-exo-trig processes in which a pseudoequatorial configuration is normally adopted, and has been attributed to the steric influence imposed by the bulky tert-butyldiphenylsilyloxy chiral auxiliary allylic to the enoate ester. The product stereochemistries provide models for the required cis-stereochemistry of the D/E ring fusion of the Tacaman alkaloid skeleton via the relatively unexplored C-3-C-14 bond disconnection.
Hunter
Roger
R
Department of Chemistry University of Cape Town, Rondebosch 7701, Cape Town, South Africa. Roger@science.uct.ac.za
Richards
Philip
P
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000838:Anions / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005609:Free Radicals / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis*; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism
D000470:Alkaloids; D000838:Anions; D005609:Free Radicals; D007211:Indoles