Copper-Catalyzed Domino Annulation Reaction to Benzoxazoles

Significance

A domino annulation strategy for the synthesis of benzoxazoles has been investigated. Initially, 1,2-dihaloarenes were used as substrates in Cu-catalyzed cross-coupling of acid chlorides with primary amides. This route was deemed ineffective due to the inaccessibility of 1,2-dihaloarenes and regioselectivity problems. Therefore, a one-pot domino annulation using 2-bromoanilines and acyl chlorides as reactants was developed. Combinations of different solvents, ligands and bases were studied, and 1,10-phen­anthroline, Cs₂CO₃ and MeCN turned out to give the highest yields. Microwave irradiation was the most efficient heating method in attaining the high temperature required, as lower temperatures led to incomplete conversion. The yields reported range from poor to very high and the substrate scope was sufficiently studied. No reactions with o-chloro- or o-iodoanilines were reported.