Studies Towards CD Intermediates of Vitamin D₃: Enolate Trapping of Ketone Enolates With Novel Sulfonyl Electrophiles

Abstract

The phenyl sulfonyl electrophile (3) reacts with the titanium enol of cyclopentanone to provide an alkylated adduct (8). Conversion into the model hydrindanol (11) [71% from (8)] was readily effected by hydrogenation, and subsequent annelation with potassium t- butoxide . Application of the model study to the synthesis of a CD intermediate, through the use of the conjugate addition of lithiated butenyldiphenylphosphine oxide (2) to 2-methylcyclopentenone (1), followed by trapping with the electrophile (3), was not straightforward. Hydrogenation of the adduct (12) proceeded with loss of stereoselectivity. Instead, use of the alternative electrophiles, the α-( trimethylsilyl ) butadienyl sulfones (18) and (19), gave the desilylated unsaturated adduct (22). Hydrogenation of (22) proceeded smoothly to give the saturated adduct (15) as one isomer. However, in contrast to the model study, attempts at cyclization of the CD intermediate precursor (15) were unsuccessful.