Tandem Sequence of Phenol Oxidation and Intramolecular Addition as a Method in Building Heterocycles

摘要

A tandem phenol oxidation−Michael addition furnishing oxo- and -aza-heterocycles has been developed.nDirhodium caprolactamate [Rh2(cap)4] catalyzed oxidation by T-HYDRO of phenols with alcohols, ketones, amides, carboxylicnacids, and N-Boc protected amines tethered to their 4-position afforded 4-(tert-butylperoxy)cyclohexa-2,5-dienones that undergonBrønsted acid catalyzed intramolecular Michael addition in one-pot to produce oxo- and -aza-heterocycles in moderate to goodnyields. The scope of the developed methodology includes dipeptides Boc-Tyr-Gly-OEt and Boc-Tyr-Phe-Me and provides anpathway for understanding the possible transformations arising from oxidative stress of tyrosine residues. A novel method ofnselective cleavage of O−O bond in hindered internal peroxide using TiCl4 has been discovered in efforts directed to thenconstruction of cleroindicin F, whose synthesis was completed in 50% yield over just 3 steps from tyrosol using the developednmethodology.