Diaryl ether containing N-hydroxycarbamates from nitroso cycloadducts

Regioselective ring opening of N-hydroxycarbamate-derived nitroso cycloadducts by a copper-catalyzed allylic alkylation reaction was achieved and applied to the synthesis of a set of substituted diaryl ether containing compounds. Use of protected 3-hydroxybenzyl bromide allowed access to a late stage phenol intermediate after protection of the N-hydroxy moiety that was generated from the ring opening reaction. The diaryl ethers were then formed by copper-mediated coupling with arylboronic acids. After selective deprotection, alumina-promoted transcarbamoylation provided the target compounds. Previous results indicate that the compounds may possess significant inhibitory potency against the proinflammatory enzyme 5-lipoxygenase.