A recurring motif in many natural products, including those with therapeutic value, is a carbon skeleton with alternating sequences of C-methyl groups without intervening hydroxy groups. A general and iterative route to these deoxypropionate fragments is proposed, using a titanocene-catalyzed asymmetric hydrogenation of a trisubstituted olefin as the key step to setting the methyl stereocenter. The trisubstituted olefin will be constructed with a protected allylic alcohol, so that following hydrogenation, deprotection and oxidation will form an aldehyde, which can then be converted to an analogous but homologated trisubstituted olefin. The iterative route is illustrated by a proposed synthesis of the C2-C10 fragment of the antibiotic (+)- Ionomycin, and by the synthesis of a key intermediate used in the synthesis of the lichen metabolite (+)-Bourgeanic Acid.
