Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part I. Asymmetric addition of malonate nucleophiles

Asymmetric alkylations of allylic geminal dicarboxylates with dialkyl malon ates have been investigated. The requisite allylic geminal dicarboxylates a re prepared in good yields and high isomene purities by two catalytic metho ds, ferric chloride-catalyzed addition of acid anhydrides to alpha,beta -un saturated aldehydes and palladium-catalyzed isomerization and addition reac tions of propargylic acetates. The complex of palladium(0) and the chiral l igand derived from the diamide of trans-1,2-diaminocyclohexane and 2-diphen ylphosphinobenzoic acid most efficiently catalyzed the asymmetric process t o provide allylic carboxylate esters with high ee. By systematic optimizati on studies, factors affecting the enantioselectivity of the reaction have b een probed. In general, higher ee's have been achieved with those condition s which facilitate kinetic capture of the incipient pi -allylpalladium inte rmediate. These conditions also proved effective for achieving high regiose lectivities. The minor regioisomeric product was formed when reactive subst rates or achiral ligands were employed for the reaction, and could be minim ized through the use of the chiral ligand. Under the established conditions , the alkylation of various gem-dicarboxylates afforded monoalkylated produ cts in high yields with greater than 90% ee. The process constitutes the eq uivalent of an addition of a stabilized nucleophile to a carbonyl group wit h high asymmetric induction.