Synfacts 2011(3): 0249-0249  
DOI: 10.1055/s-0030-1259564
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart ˙ New York

Rhodium(III)-Catalyzed Heteroannulation Route to Isoquinolines

Contributor(s): Victor Snieckus, Emilie David
P. C. Too, Y.-F. Wang, S. Chiba*
Nanyang Technological University, Singapore
Further Information

Publication History

Publication Date:
16 February 2011 (online)


Reported is the rhodium(III)-catalyzed synthesis of isoquinolines 3 from the reaction of O-acetyloximes 1 with alkynes 2 using a [Cp*RhCl2]2/NaOAc catalytic system. The reaction proceeds in good yields with diphenylacetylene using a wide range of R² = EDGs and EWGs. In case of meta R² substituents, a mixture of regio­isomeric isoquinoline 3 products was obtained. Unsymmetrical and dialkyl-substituted alkynes also afforded the isoquinolines, albeit in modest yields. Based on deuteriation studies, a mechanism involving ortho C-H activation of O-acetyl­oximes 1 via the oxime sp² nitrogen was proposed. Regioselective insertion of the alkyne into the arylrhodium intermediate leads to the formation of a seven-membered rhodacycle, which finally undergoes C-N reductive elimination. Analogously, isoxazol-5-ones 4 also undergo direct ortho-rhodation affording isoquinolines 5 with different R7 groups.