Desymmetrisation of meso-methylcyclooctanones. Highly Enantioselective Synthesis of C8 syn-Isoprenoid and syn,syn-Deoxypropionate Subunits from a Bicyclo[3.3.1]nonane Precursor

The methyl esters of 3R,7S-dimethyl- and 3R,5R,7S-trimethyl-8-hydroxyoctanoic acids have been prepared in good yields and with e.e. >98% by chemical elaboration of the known exo,exo-3,7-dimethylbicyclo[3.3.1]nonan-9-one, the key step involving the desymmetrisation of the intermediate meso-ketones cis-3,7-dimethyl- and cis,cis-3,5,7-trimethyl-cyclooctanone through the corresponding chiral enolates generated by the lithium amide of the (+)bis[(R)-(1-phenylethylamine)]. The very high enantioselectivity observed might be related to the conformational features of the eight-membered ring.