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 α,β‐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, ¹⁹F MAS‐NMR and ¹⁹F 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.