Lithium enolates from a (−)-quinic acid-derived cyclohexanone with a β-alkoxy leaving group: regioselective preparation and evaluation of enolate stability towards β-elimination

Deprotonation of a (−)-quinic acid-derived ketone {(2S,3S,4aR,8R,8aS)-8-(tert-butyl(dimethyl)silyl)oxy]-2,3-dimethoxy-2,3-dimethylhexahydro-1,4-benzodioxin-6(5H)-one} using lithium hexamethyldisilazide (LHMDS) at −78 °C gave one regioisomeric enolate. The regiocontrol is governed by the axial β-silyloxy substituent and the resulting lithium enolate is stable towards β-elimination at temperatures up to −40 °C. It was found that the axial β-silyloxy group could be conveniently eliminated using 2.1 equiv of LHMDS at 0 °C for 1 h and that an equatorial β-alkoxy group was much more resistant to β-elimination. A chiral lithium amide base was used to overturn the inherent regioselectivity of ketone deprotonation with LHMDS.