861. Terpene synthesis. Part III. Benzyloxymethylation as a method of synthesis of terpene carboxylic acids

Abstract

Benzyloxymethylation of ketones of the type (IV; R = H or CH,O) is shown to be highly stereoselective in favour of production of the a-substituted derivative (V) and is applied to the synthesis of ( j-)-dehydrodeisopropylabietic acid and of an isomer of ( -J-)-podocarpic acid methyl ether. BENZYLOXYMETHYLATION of ketones, as in (I) + (11), has been described as an alkylation procedure for the introduction of the hydroxymethyl and derived groups in terpene synthesis. We have now examined the value and limitations of this method for the elaboration of acids of the type (111) via benzyloxymethylation of the related ketones (IV; R = H or CH30).Stereoselectivity of alkylation, depending on the principle of least-hindered approach, has been found, in simpler instances, to be reversed by the presence of a polar substituent, e g . , (VI; R = Me) -(VII),h and (VI; R = C0,Et) + (VIII).a Selectivity is also rather sensitive to relatively minor structural change^.^ In (IV) the aromatic residue introduces a steric constraint and in comparison with (VI) removes two axial substituents. In fact the compounds (IV; R = H or CH,O) undergo specific a-alkylation.