A Conceptually Different Approach to the Asymmetric Synthesis of α-Substituted Carbonyl Compounds

A new approach has been demonstrated for the asymmetric synthesis of α-substituted carbonyl compounds. Thus, the key asymmetric carbon-carbon bond formation is accomplished by the highly diastereoselective addition of organoaluminum reagents to the chiral α,β-unsaturated acetal derived from the α,β-unsaturated aldehyde and (R,R)-tartaric acid diamide to furnish the 1,4-adduct preferentially along with the 1,2-adduct as a minor product. Subsequent oxidation of the combined adducts with ozone or the system potassium permanganate/sodium periodate gives rise to the optically active α-substituted aldehyde, ketone, or carboxylic acid, respectively, with high enantioselectivities. The present method has been applied to the facile synthesis of an anti-inflammatory agent and the principal alarm pheromone of the leaf-cutting ant Atta texana in optically active forms.