Synthesis of isoquinolines and pyridines by the palladium-catalyzed iminoannulation of internal alkynes.
A wide variety of substituted isoquinoline, tetrahydroisoquinoline, 5,6-dihydrobenz[f]isoquinoline, pyrindine, and pyridine heterocycles have been prepared in good to excellent yields via annulation of internal acetylenes with the tert-butylimines of o-iodobenzaldehydes and 3-halo-2-alkenals in the presence of a palladium catalyst. The best results are obtained by employing 5 mol % of Pd(OAc)(2), an excess of the alkyne, 1 equiv of Na(2)CO(3) as a base, and 10 mol % of PPh(3) in DMF as the solvent. This annulation methodology is particularly effective for aryl- or alkenyl-substituted alkynes. When electron-rich imines are employed, this chemistry can be extended to alkyl-substituted alkynes. Trimethylsilyl-substituted alkynes also undergo this annulation process to afford monosubstituted heterocyclic products absent the silyl group.
Roesch
K R
KR
Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA.
Zhang
H
H
Larock
R C
RC
D000470:Alkaloids / Q000138:chemical synthesis; D000480:Alkynes / Q000737:chemistry; D002384:Catalysis; D007546:Isoquinolines / Q000138:chemical synthesis*; D010165:Palladium / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis*
D000470:Alkaloids; D000480:Alkynes; D007546:Isoquinolines; D011725:Pyridines; D010165:Palladium