Organocatalytic Activation of Pyruvates Toward Michael Addition to Nitroalkenes: Synthesis of -Aminobutyric Acid (GABA) Derivatives

Despite the significant role of pyruvic acid in biotransformations, the utilization of pyruvates in the field of catalytic asymmetric synthesis has been unexpectedly limited. This statement also applies to enamine catalysis, in which pyruvates seem to be challenging substrates. Recently, the first illustration of the asymmetric addition of pyruvic acid to beta-nitrostyrenes, catalyzed by a NahE enzyme using the enamine mechanism, has appeared in the literature. Now, we demonstrate pyrrolidine-based catalyst can mimick enamine mechanism used by this enzyme to activate pyruvates in the asymmetric addition to structurally diverse nitroalkenes to produce highly enantioenriched Michael adducts without the limitations in substrate structures associated with biocatalysts. In addition to confirming that optically pure pyrrolidines can serve as ultimately small organic catalysts in pyruvate activation, we present an exceedingly simple and versatile method for the synthesis of optically pure gamma-nitro acids, which are precursors for well-known active pharmaceutical ingredients namely GABA derivatives image