Cu(I) catalyzed microwave assisted telescopic synthesis of 3,5-disubstituted isoxazoles in green media

Abstract

A facile and efficient microwave assisted telescopic synthesis of diverse isoxazoles was reported in green reaction medium. Initially, N-hydroxyl imidoyl chlorides were reacted with substituted alkynes in aqueous medium using 2mol% of [Cu(phen)(PPh3)2]NO3 as catalyst to yield the 3,5-disubstituted isoxazoles. To improve the efficiency of the synthetic route for the regioselective synthesis of isoxazoles, commercially available aromatic aldehydes were converted to N-hydroxyl imidoyl chlorides followed by reaction with substituted alkynes in aqueous medium using Cu(I) as catalyst in telescopic manner. This telescopic new synthetic strategy facilitates the rapid generation of molecular frameworks in three-dimensional fashion leading to 3,5-disubstituted isoxazoles. This approach is visualized as an environmentally benign process and a simple operation to the privileged scaffolds. The present one-pot synthetic sequence allows the introduction of two points of structural diversity to expand chemical space with excellent purity and yields.