Asymmetric Michael additions of α-cyanoacetates by soft Lewis acid/hard Bronsted acid catalysis: stereodivergency with bi- vs. monometallic catalysts

The direct asymmetric conjugate addition of alpha-cyanoacetates to enones generating densely functionalized alpha-amino acid precursors with adjacent quaternary and tertiary stereocenters is described comparing mono- and bis-palladacycle catalysts. This edge article features the complementary value of mono- and bimetallic catalysis in a case study using related catalyst systems. Different major diastereomers of the 1,4-addition products are formed by the use of the planar chiral mono- and bimetallic catalyst systems and provide access to epimeric amino acid derivatives. Both catalyst types require the use of a Bronsted acid (HOAc) as a co-catalyst to avoid an undesired beta-hydride elimination. Kinetic studies show that the C-C bond forming step takes place almost instantaneously with the bis-palladium complex after productive substrate coordination. This extraordinarily high reactivity for an elementary step generating a sterically demanding linkage of a quaternary and a tertiary stereocenter stresses the cooperativity of both metal centers.