A stepwise lactol carbocyclisation to bridged ethers via a keto–acetal cascade

Abstract

Lactol carbocyclisations provide a succinct method of constructing the oxabicyclo[3.2.1]octane scaffold, a motif present in various natural products of medicinal interest. Lactols containing an unsaturated ketone or ester were prepared by olefin cross-metathesis; an electrophilic alkene derived from methyl vinyl ketone underwent concomitant terminal α-methylenation and oxa-Michael addition to give a bridged lactol which then underwent oxygen-to-carbon transposition in the presence of titanium (IV) chloride giving the desired unsaturated carbocyclic seven-membered bridged ether via a novel dehydrative cascade considered to involve titanium enolates.