Asymmetric Decarboxylative Protonation and Deuteration of Cyanoacetic Acids Using an Organometallic Proton Shuttle

The trajectory of proton is hard to control. Chiral catalysts known as "proton shuttles" are key to reactions involving proton transfers by hosting a proton and enabling its stereoselective addition. Although organic acids and bases are commonly used for this purpose, we demonstrate here that a rhodium-phosphoramidite complex can serve as an organometallic proton shuttle to intercept the deprotonation/CO₂ extrusion/protonation sequence in the decarboxylation of cyanoacetic acids and dictate its stereochemistry. While the amino motif in the ligand accommodates the proton, the nearby rhodium helps fix the orientation of the ketenimine intermediate for protonation via a dative bond. Furthermore, the decarboxylation pathway is compatible with H/D exchange using deuterated solvent, thus allowing an asymmetric decarboxylative deuteration. This method bridges the bulk production of cyanoacetates and their facile substitution with postdecarboxylation transformations of nitrile to access structurally diverse stereocenters and deuterated entities.