An organo-NHC catalyzed domino addition approach for the selective synthesis of 5-butynylisoxazoles and subsequent Sonogashira coupling

Abstract

A nucleophilic organo N-heterocyclic carbene (NHC) catalysed click-type fast domino addition of allenyl-MgBr to aryl nitrile oxides to produce 5-butynylisoxazoles with excellent selectivity and good yields is reported. The unwanted protonation and subsequent formation of 5-methylisoxazole byproducts is successfully suppressed. Furthermore, a Pd/Ag catalysed protocol for Sonogashira cross-coupling of 5-butynylisoxazoles to obtain the corresponding internal alkynes with high selectivity and yields is developed by minimising the alkyne homo-coupling.