Bimetallic [Co/K] hydrogen evolution catalyst for electrochemical terminal C-H functionalization

Abstract

Discovering novel catalysts for hydrogen evolution reaction (HER) holds the potential to revolutionize the energy chemistry and unlock new tool for synthetic processes. Inspired by hydrogenases, we pair alkali metals with cobalt-Salen catalysts which allow the integration of naked base site into bimetallic HER catalysts. The incorporation of alkali metals (Na, K, Rb, Cs) significantly enhances HER activity. Among these, the [Co/K] system exhibits the highest HER catalytic efficiency (k_obs ~ 31.4 s⁻¹), which is 9 times higher than the mononuclear analogue. Remarkably, this HER catalyst is repurposed for the terminal C(sp³)-H functionalization of N-allylimines with imine/aldehyde, a previously inaccessible transformation. Mechanistic studies reveal that the naked base site enables selective C-H activation via proton relay, overriding the inherent preference for Pinacol coupling. The electrochemical protocol features good functional group tolerance, and opens up a streamlined avenue for chiral pyrrolines, key precursors of the anti-cancer medicine Larotrectinib. More importantly, the alkali metal effect is rationalized through structural analysis, density functional theory (DFT) calculations, and control experiments.

Fig. 1. Strategies for HER catalyst finding and the C–H functionalization of N-allylimine.

a The structure of [NiFe] and [FeFe] hydrogenases. b Reported strategies for HER catalysts. c The structure of cobalt/alkali-Salen HER catalyst. d The C–H functionalization of N-allylimine. AM alkali metal.

Fig. 2. Synthesis and HER activity of cobalt/alkali-Salen catalysts.

a Synthetic route of cobalt/alkali-Salen catalysts. b Single-crystal structure of cat 2. c The chemical shifts of the protons in the HER catalysts. d Redox potentials of catalysts. e Cyclic voltammograms of HER catalyst (0.01 mmol) and acetic acid (0.175 mmol) in DMF (3.0 mL) solution with ⁿBuNClO₄ as electrolyte. DMF N,N-dimethylformamide, Fc ferrocene.

Fig. 3. Scope of terminal C–H functionalization of N-allylimine.

Reaction conditions: 1 (1.5 mmol), 2 (0.5 mmol), cat 2 (5 mol%), ⁿBu₄NClO₄ (1.0 mmol), DMF (10 mL), graphite felt anode, nickel plate cathode, undivided cell, CCE = 18 mA, 3 h (4.03 F/mol), 0 ^°C; Yields were based on isolated products; dr > 15/1, unless otherwise noted. ^aThe reaction is conducted on a 0.3 mmol scale. GF graphite felt, CCE constant current electrolysis, DMF N,N-dimethylformamide.

Fig. 4. Utility of the [Co/K] catalyzed protocol.

a Electrochemical terminal C–H functionalization of N-allylimine with aldehydes. b Gram-scale reaction and product derivatization.

Fig. 5. Cyclic voltammetry and control experiments.

a Cyclic voltammogram of 1a (0.05 mmol), 2a (0.05 mmol) and benzaldehyde (0.05 mmol) in DMF (3.0 mL) solution with ⁿBuNClO₄ as electrolyte. b Cyclic voltammogram of 1a (0.05 mmol) and cat 2 in DMF (3.0 mL) solution with ⁿBuNClO₄ as electrolyte. c Cyclic voltammogram of cat 2 (0.01 mmol) and 1a in DMF (3.0 mL) solution with ⁿBuNClO₄ as electrolyte. d Cyclic voltammogram of cat 2 (0.01 mmol) and HOAc in DMF (3.0 mL) solution with ⁿBuNClO₄ as electrolyte. e Control experiments. Fc ferrocene, DMF N,N-dimethylformamide, TEMPO 2,2,6,6-Tetramethylpiperidinooxy.

Fig. 6. Reaction mechanism.

a Proposed catalytic cycle for the electrochemical functionalization. b DFT calculations for the catalytic species. c DFT calculations for the nucleophilic addition between carbanions and Ellman imine. DFT density functional theory.