An Approach to Highly Functionalized Quinolines and Isoquinolines via a Gold-Catalyzed Benzannulation

Abstract

The AuCl₃-catalyzed benzannulation of pyridine-­containing oxo-alkynes with external as well as internal alkynes proceeds under mild conditions, and a variety of quinoline and isoquinoline derivatives are produced in good to excellent yields. The reaction proceeds through the formation of aza-isobenzopyrylium auric ate complexes as evident from trapping experiments.

Key words

gold - catalysis - benzannulation - quinolines - isoquinolines

References and Notes

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11

Indeed 1a was found to react exothermally when brought in contact with DMAD in DCE at a similar concentration.

12

Oxo-alkynes 1a-d were prepared from the corresponding pyridine-2-chloro aldehydes by Sonogashira coupling; similarly, 1e was prepared from iodoaldehyde 3 by Sonogashira coupling.

14

An alkyne with an aryl and an ester substituent, e.g., PhCºCCO₂Me was found not to react either with the electron-rich oxo-alkyne 1a or the electron-deficient oxo-alkyne 1e; presumably in this case the HOMO-LUMO energy difference is too high for both pairs of reactants.

15

This Sonogashira coupling was unsuccessful (<10%) under the classical conditions [PdCl₂(PPh₃)₂/CuI] using a variety of bases such as Et₃N, i-Pr₂NH, K₂CO₃, or NaHCO₃.

18

Even carrying out the reaction at a lower temperature (0-15 ˚C) did not give any traces of the [3+2] product 6.