A Domino Aza-Piancatelli Rearrangement/Intramolecular Diels-Alder Reaction: Stereoselective Synthesis of Octahydro-1 H-cyclopenta[ cd]isoindole.

For the first time, an efficient one-pot method for the construction of an angularly fused 5-6-5 aza-tricyclic framework has been developed in a highly stereoselective manner. This domino reaction is a novel combination of aza-Piancatelli rearrangement and intramolecular Diels-Alder reaction, which readily furnishes hexahydro-2a,5-epoxy-cyclopenta[ cd]isoindole adducts, bearing six contiguous stereogenic centers in very good yields. The BBr-mediated cleavage of the oxa-bridged adduct results in the formation of octahydro-1 H-cyclopenta[ cd]isoindole, an aza-tricyclic BCE core of a gracilamine alkaloid.