α-Branched Ketone Dienolates: Base-Catalysed Generation and Regio- and Enantioselective Addition Reactions

In this study, the unique capacity of bifunctional BrOnsted bases to generate alpha-branched ketone dienolates and control both site- and stereoselectivity of their addition reactions to representative classes of carbon electrophiles (i.e., vinyl sulfones, nitroolefins, formaldehyde) is documented. We demonstrate that by using selected chiral tertiary amine/squaramide catalysts, the reactions of beta,gamma-unsaturated cycloalkanones proceed through the dienolate C alpha almost exclusively and provide all-carbon quaternary cyclic ketone adducts in good yields with very high enantioselectivities. A minor amount (<5%) of gamma-addition is observed when nitroolefins are used as electrophiles. The parent acyclic ketone dienolates proved to be less reactive under these conditions, and thus still constitute a challenging class of substrates. Quantum chemical calculations correctly predict these differences in reactivity and explain the observed site-specificity and enantioselectivity.