Facile Protocols towards C2-Arylated Benzoxazoles using Fe(III)-Catalyzed C(sp2-H) Functionalization and Metal-Free Domino Approach

Considering their growing attention in the field of medicinal chemistry and drug-discovery research, the facile and convenient approaches towards the preparation of 2-aryl benzoxazole derivatives have been described. The transformation is accomplished by using Fe(III)-catalyzed C-H activation of benzoxazoles with boronic acids to obtain a wide range of C2-arylated benzoxazoles in high yields. The developed method excludes the formation of self-coupling compounds as side products. On the other hand, the synthesis of the products is also achieved via a metal-free domino protocol by the reaction between 1-nitroso-2-naphthol and acetophenones using catalytic amounts of CBr4 in the presence of Cs2CO3 as base. The devised tandem method avoids the use of pre-activated alpha-haloketones as substrates. Due to their immense impact in marketed drugs and molecules under clinical trial, the described method can be a powerful tool for their synthesis which restricts the use of precious metals as catalyst.