Synthesis of isoindolo[2,1-alpha]indoles by the palladium-catalyzed annulation of internal acetylenes

A wide variety of substituted isoindolo[2,1-alpha ]indoles have been prepar ed via annulation of internal alkynes by imines derived from o-iodoanilines in the presence of a palladium catalyst. This methodology provides an extr emely efficient route for the synthesis of these tetracyclic heterocycles f rom readily available starting materials. The mechanism of this interesting annulation process appears to involve (1) oxidative addition of the aryl i odide to Pd(0), (2) alkyne insertion, (3) addition of the resulting vinylic palladium intermediate to the C-N double bond of the imine, (4) either ele ctrophilic palladation of the resulting a-palladium intermediate onto the a djacent aromatic ring derived from the internal alkyne or oxidative additio n of the neighboring aryl carbon-hydrogen bond, and (5) reduction of the te tracyclic product and Pd(0). A variety of internal acetylenes have been emp loyed in this annulation process in which the aromatic ring of the alkyne c ontains either a phenyl or a heterocyclic ring.