Remote stereocontrol in the Nazarov reaction: a new approach to the core of roseophilin

Three different procedures are compared to obtain properly substituted divinyl ketones in which one of the double bonds is embedded in a five-membered heterocyclic structure and therefore suitable to produce cyclopenta-fused pyrrole derivatives by the acid-catalyzed Nazarov reaction. These, on treatment with TFA, afforded 2,4-cis-disubstituted 2,3,4,5-tetrahydro-1H-cyclopentab]pyrrol-6-ones with high stereocontrol. One of these Nazarov products was oxidized to the corresponding 4,5-dihydro-1H-cyclopentab]pyrrol-6-one derivative, thus obtaining an enantiopure key intermediate in the total synthesis of roseophilin.