Pd/Cu Catalyzed Asymmetric Allylation for Stereodivergent Synthesis of Glutamic Acid Derivatives

A synergistic Pd/Cu catalyst system has been developed for stereodivergent transformation of Morita-Baylis-Hillman (MBH) carbonates and Schiff bases derived from simple amino acids to afford a series of optically active β-branched γ-methyleneglutamic acid derivatives with adjacent tertiary/tertiary and quaternary/tertiary stereocenters in high yields (up to 96 %) with excellent diastereo- and enantioselectivities (>20/1 dr and >99 % ee in most cases) under mild conditions. The use of SKP ligand is disclosed to be crucial for the success of the transformation, and in particular allowing the reaction to proceed at low catalyst loading (0.02 mol % for Pd and 0.08 mol % for Cu). The high efficiency of the catalysis was attributed to the formation of intimate ion pair complex A1, composed of Pd-phosphonium cation and a t-butoxide anion, which would facilitate the subsequent deprotonation and C-C coupling events. All four stereoisomers of the β-branched glutamic acid derivatives were readily prepared by permutation of the catalyst enantiomers. Synthetic utility of the methodology was exemplified by efficient synthesis of a fused pyrrolooxazolidinone with three contiguous chiral centers, highlighting the power of synergistic Pd/Cu catalysis for asymmetric allylic alkylation with MBH carbonates.