Copper(i)-catalyzed tandem synthesis of 4,5-functionalized oxazoles from isocyanoacetate and aldehydes†
Abstract
Oxazoles are among the most important heterocyclic scaffolds in the fields of natural products and medicinal chemistry. Herein is developed a tandem reaction for the synthesis of a diverse array of 4,5-difunctionalized oxazoles utilizing easily-accessible ethyl 2-isocyanoacetate and aldehydes (26 examples, 31–83% yields). This cascade reaction is facilitated by catalytic CuBr and molecular oxygen as the oxidant. The process involves a catalytic cycloaddition oxidative dehydroaromatization mechanism. The broad aldehyde substrate scope, mild reaction conditions, and atom economy make this protocol an attractive alternative to access functionalized oxazoles.