Synthesis of isoquinolines and pyridines by the palladium-catalyzed iminoannulation of internal alkynes

A wide variety of substituted isoquinoline, tetrahydroisoquinoline, 5,6-dih ydrobenz[f]isoquinoline, pyrindine, and pyridine heterocycles have been pre pared in good to excellent yields via annulation of internal acetylenes wit h the tert-butylimines of o-iodobenzaldehydes and 3-halo-2-alkenals in the presence of a palladium catalyst. The best results are obtained by employin g 5 mol % of Pd(OAc)(2), an excess of the alkyne, 1 equiv of Na2CO3 as a ba se, and 10 mol % of PPh3 in DMF as the solvent. This annulation methodology is particularly effective for aryl- or alkenyl-substituted alkynes. When e lectron-rich imines are employed, this chemistry can be extended to alkyl-s ubstituted alkynes. Trimethylsilyl-substituted alkynes also undergo this an nulation process to afford monosubstituted heterocyclic products absent the silyl group.