Copper-catalyzed domino annulation approaches to the synthesis of benzoxazoles under microwave-accelerated and conventional thermal conditions.
Two domino annulation approaches for benzoxazole synthesis have been developed. In the first approach, copper-catalyzed intermolecular cross-coupling of 1,2-dihaloarenes with primary amides initially forms the Ar-N bond of the benzoxazole ring, followed by copper-catalyzed intramolecular cyclization to form the Ar-O bond. Benzoxazoles were formed in good yields for the reaction of 1,2-dibromobenzene, but the reaction was not regioselective for the reaction of 3,4-dibromotoluene. Furthermore, the method is limited by the availability of 1,2-dihaloarenes. As a result of these limitations, an alternative more versatile one-pot domino annulation strategy was developed involving reaction of 2-bromoanilines with acyl chlorides in the presence of Cs2CO3, catalytic CuI, and the non-acylatable ligand 1,10-phenanthroline. Under these conditions initial acylation of the aniline is followed by copper-catalyzed intramolecular cyclization of the resultant 2-haloanilide to form the Ar-O bond of the benzoxazole ring. Optimized conditions using microwave irradiation achieved much shorter reaction times than conventional heating (i.e., 210 degrees C for 15 min versus 95 degrees C for 24 h) and were applied to the synthesis of a small library of benzoxazoles. These copper-catalyzed approaches complement existing strategies for benzoxazole synthesis, which typically utilize 2-aminopheonls as precursors.
Viirre
Russell D
RD
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
Evindar
Ghotas
G
Batey
Robert A
RA
D000215:Acylation; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D008872:Microwaves; D015394:Molecular Structure; D013696:Temperature
D001583:Benzoxazoles; D001688:Biological Products; D003432:Cross-Linking Reagents; D003300:Copper