Transition-Metal-Free S_NAr-Type Synthesis of Chromones

Significance

This report represents a caveat publication. Aiming to develop a copper-catalyzed synthesis of chromones 2 via an intramolecular ­Ullmann O-arylation of (ortho-halophenyl)propane-1,3-diones 1, Fu and co-workers, to their credit, carried out a control experiment without a copper catalyst. This led to the discovery that the O-arylation proceeded more efficiently without the aid of a transition metal, thus representing a normal intramolecular S_NAr process. The reaction was carried out under basic conditions (K₂CO₃, Na₂CO₃, K₃PO₄) in polar aprotic solvents (DMF, DMSO, NMP); the combination of K₂CO₃ and DMF giving the best results. Surprisingly, aryl ­bromides were more reactive than aryl chlorides, although both gave good to high yields of chro­mone products. Starting materials 1 with R^² = aryl groups gave higher yields compared to R^² = aliphatic ones. Also, R^¹ = EDG showed lower reactivity. Control experiments showed that 1) oxygen has no effect on the reaction and 2) the reaction does not proceed through a radical pathway. Surprisingly, the simple intermolecular O-arylation of 1-bromo-2-nitrobenzene with phenol under the same conditions failed.