The Imidato-Alkenyllithium Route for the Synthesis of the Isoquinocycline-Pyrrolopyrrole Substructure

A convergent and effective synthesis of the pyrrolopyrrole substructure (CDEFG) of the isoquinocyclines is reported. A key step is a tin−lithium exchange of an imidato-alkenyltin compound (a ring G equivalent) and the subsequent acylation with a lactone. The resulting acetal is used successfully for the ring F closure to the pyrrolopyrrole. The sole formation of the isoquinocycline N,O-acetal epimer is in accordance with the proposed mechanism for the isomerization of quinocyclines to isoquinocyclines.