λ 3-Iodane-mediated arenol dearomatization. Synthesis of five-membered ring-containing analogues of the aquayamycin ABC tricyclic unit and novel access to the apoptosis inducer menadione

Abstract

The λ 3-iodane [bis(trifluoroacetoxy)]iodobenzene (BTI)-mediated oxidative dearomatization of 2-alkoxyarenols with soft external carbon-based nucleophiles constitutes a rapid access to highly functionalized naphthoid cyclohexa-2,4-dienones. These synthons can serve as valuable intermediates in the construction of the angularly-oxygenated benz[ a]naphthalene ABC ring system of aquayamycin- and SS-228Y-type antibiotic angucyclinones, and analogues thereof. This methodology led to the elaboration of five-membered A ring-containing analogues of this ABC tricyclic unit. In addition, the BTI-mediated oxidative activation of 2-methylnaphthol can be exploited to prepare menadione (i.e. vitamin K 3), known to induce apoptosis and autoschizis, a novel type of cancer cell death.