A Domino Copper-Catalyzed C-N and C-O Cross-Coupling for the Conversion­ of Primary Amides into Oxazoles

Abstract

A variety of oxazoles can efficiently be prepared, in a single step and in good yield, from primary amides and 1,2-dihaloalkenes using copper-catalysis. This new method allows the re­gioselective formation of a range of substituted oxazoles. The required 1,2-dihaloalkenes can prepared by simple treatment of alkynes with elemental bromine or iodine.

Key words

oxazoles - C-N and C-O cross-coupling - copper - cyclization - domino reaction - heterocycles

References

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7

Parameters screened: Ligands: DMEDA (optimal), rac-1,2-diaminocyclohexane (lower conversion, more side products), phenanthroline (no reaction); bases: K₂CO₃ (optimal), K₃PO₄ (lower conversion, more side products), Cs₂CO₃ (lower conversion), Et₃N and NaOAc (no reaction). Reaction temperature: <110 °C conversion was found to be incomplete; solvents: toluene (optimal), chlorobenzene (lower conversion), t-BuOH, dioxane (much lower conversion), DMF (no conversion).