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

Article abstract of DOI:10.1021/ja003774o

Asymmetric alkylations of allylic geminal dicarboxylates with dialkyl malonates have been investigated. The requisite allylic geminal dicarboxylates are prepared in good yields and high isomeric purities by two catalytic methods, ferric chloride-catalyzed addition of acid anhydrides to α,β-unsaturated aldehydes and palladium-catalyzed isomerization and addition reactions of propargylic acetates. The complex of palladium(0) and the chiral ligand derived from the diamide of trans-1,2-diaminocyclohexane and 2-diphenylphosphinobenzoic acid most efficiently catalyzed the asymmetric process to provide allylic carboxylate esters with high ee. By systematic optimization studies, factors affecting the enantioselectivity of the reaction have been probed. In general, higher ee's have been achieved with those conditions which facilitate kinetic capture of the incipient π-allylpalladium intermediate. These conditions also proved effective for achieving high regioselectivities. The minor regioisomeric product was formed when reactive substrates or achiral ligands were employed for the reaction, and could be minimized through the use of the chiral ligand. Under the established conditions, the alkylation of various gem-dicarboxylates afforded monoalkylated products in high yields with greater than 90% ee. The process constitutes the equivalent of an addition of a stabilized nucleophile to a carbonyl group with high asymmetric induction.