Nucleophilic β-Carbon Activation of Propionic Acid as a 3-Carbon Synthon by Carbene Organocatalysis

Direct β-carbon activation of propionic acid (C₂H₅CO₂H) by carbene organocatalysis has been developed. This activation affords the smallest azolium homoenolate intermediate (without any substituent) as a 3-carbon nucleophile for enantioselective reactions. Propionic acid is an excellent raw material because it is cheap, stable, and safe. This approach provides a much better solution to azolium homoenolate synthesis than the previously established use of acrolein (enal without any substituent), which is expensive, unstable, and toxic. The littlest homoenolate: A route to the smallest azolium homoenolate intermediate has been developed from a simple and cheap raw material - propionic acid. Carbene-catalyzed β-carbon activation successfully converts propionic acid as a 3-carbon nucleophile for enantioselective reactions.