Catalytic Stereoselective 1,4-Addition Reactions Using CsF on Alumina as a Solid Base: Continuous-Flow Synthesis of Glutamic Acid Derivatives

A novel methodology using CsF?Al2O3 as a highly efficient, environmentally benign, and reusable solid-base catalyst was developed to synthesize glutamic acid derivatives by stereoselective 1,4-addition of glycine derivatives to alpha,beta-unsaturated esters. CsF?Al2O3 showed not only great selectivity toward 1,4-addtion reactions by suppressing the undesired formation of pyrrolidine derivations by [3+2] cycloadditions, but also offered high yields for the 1,4-adduct with excellent anti diastereoselectivities. The catalyst was well characterized by using XRD, F-19 MAS-NMR and F-19 NMR spectroscopy, FT-IR, CO2-TPD, and XPS. And highly basic F from Cs3AlF6 was identified as the most probable active basic site for the 1,4-addition reactions. Continuous-flow synthesis of 3-methyl glutamic acid derivative was successfully demonstrated by using this solid-base catalysis.