Hydrogen Bonding Enabled C-H Polarization for Multi-Site Concerted Electron-Proton Transfer in Electrochemical Dimerization of β-Ketoester.

We present the first report of direct electro-oxidation of the α-CH bond of β-ketoesters employing a multisite concerted electron-proton transfer (MS-CEPT) mechanism to access dimerized products through C(sp3)-C(sp3) bond formation. The sustainable approach utilized a graphite anode and a Pt cathode, employing acetonitrile and methanol solvents, NH4PF6 electrolyte, and NaH as a base at a constant potential of 1.8 V for 3 h. The MS-CEPT mechanism involved H+ transfer to the base (NH3) associated through hydrogen bonding with the α-CH bond and simultaneous transfer of an electron to the electrode, representing the inaugural instance of nonpolar C-H bond functionalization in a direct electro-oxidative environment. UV-vis studies provided evidence for hydrogen bonding between carbonyl groups of β-ketoesters and methanol or NH4+, resulting in polarization of the α-CH bond. NMR experiments demonstrated that this polarization led to H-bonding between the α-CH proton and in situ-generated NH3, revealing preassociation between the substrate and the base, a primary requirement for the operation of the MS-CEPT mechanism. High electrochemical isotopic current ratio (H/D) (∼1.7) supported the H+ transfer event in the rate-determining step. Twenty-one examples having diverse substituents with average yields of 73% have been provided. Dimeric β-ketoesters were further utilized in the total syntheses of naturally occurring dihydrocubebin and epi-dihydrocubebin.