Regiospecific enolates from tetrahydropyran-3-one. Synthetic equivalents of a thermodynamically and kinetically disfavoured enolate isomer

Two synthetic equivalents of the tetrahydropyran-3-one enolate 3 are described. Lithiation of the methoxy enol ether 8b provides the β-lithiated enol ether 10 and although this species does serve as an equivalent of the enolate 3, its use is limited by the observation that the mode of the acid-catalysed hydrolysis of the adducts 11 is controlled by the ‘endo’ enol ether function. Using similar chemistry to that described for the synthesis of the methoxy derivative, the isomerically pure silyl enol ether 19 has also been prepared. This reagent represents a more general solution to the synthetic problems associated with access to the enolate 3 and reacts with a range of electrophiles in Lewis acid-mediated processes.