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.