The depletion of fossil fuels and their environmental impact necessitate exploring sustainable alternatives. Biomass, abundant and renewable, offers a promising carbon source, but its complex structure requires efficient transformation strategies. While biomass-derived furanics have yielded valuable products like polymer precursors and biofuels, their economic competitiveness remains a challenge. Synthesizing high-value pharmaceuticals from biomass-derived compounds offers a more economically viable pathway. This research focuses on synthesizing heterocyclic molecules, crucial building blocks in biologically active products, from biomass-derived intermediates. While various methods exist for heterocyclic synthesis, most rely on petrochemical starting materials, expensive reagents, and harsh conditions. The Achmatowicz reaction, which converts furfuryl alcohol (obtainable from furfural, a readily available biomass derivative) into substituted dihydropyranones, is an attractive candidate. Previous approaches employing stoichiometric oxidants (Br₂, NBS, m-CPBA, DMDO) or biocatalysis (mono-oxygenase) have limitations such as the need for toxic or expensive reagents and solvents, and complex procedures. Electrochemical synthesis offers a more appealing, environmentally friendly alternative, but existing electrochemical approaches also suffer from limitations like the requirement of bromide salts, organic solvents (e.g., MeOH), low temperatures, high voltages, and post-treatment steps. This study aims to develop a more efficient and sustainable electrocatalytic approach using water as both the solvent and oxygen source.

The Achmatowicz reaction, initially reported in the 1970s, utilizes various oxidants (Br₂, NBS, m-CPBA, DMDO) and solvents (MeOH, THF, CH₂Cl₂, acetone) to convert furfuryl alcohol into substituted dihydropyranone acetals. These acetals are valuable precursors for synthesizing natural products and pharmaceuticals. The reaction introduces a chiral center, allowing for the development of asymmetric variants to synthesize diastereoselective and optically active compounds. Electrochemical methods have also been explored, but these typically require bromide salts, organic solvents, low temperatures, and high voltages, along with post-treatment steps to obtain the final hydropyranone products. The use of stoichiometric oxidants and organic solvents, often toxic or expensive, represents a significant limitation of these chemical oxidation approaches. Electrochemical methods offer an alternative, but existing methods suffer from drawbacks such as the use of bromide salts, organic solvents, low temperatures, high voltages, and post-treatment steps. This work aims to address these limitations by developing a more efficient electrocatalytic approach.

The researchers developed a heterogenized nickel electrocatalyst by immobilizing molecular active sites on an electrode. This approach combines the advantages of homogeneous catalysts (defined active sites) and heterogeneous catalysts (efficient electron transfer). They used a novel pre-immobilization strategy: 5,5'-divinyl-2,2'-bipyridine (dvbpy) was polymerized on a conductive substrate (glassy carbon or carbon paper) via UV irradiation (λ_rr = 250 nm), creating a ligand film (DVBP). Subsequent immersion in a nickel triflate solution yielded the Ni-DVBP catalyst. Various characterization techniques (FT-IR, Raman, SEM, EDS, XPS) confirmed the successful synthesis and structure of the catalyst. Electrochemical studies (CV, SWV) investigated the catalyst's behavior, revealing a pseudo-reversible Ni^3+/2+ redox couple. Bulk electrolysis in a three-electrode configuration was performed to optimize reaction conditions. Different electrolytes (phosphate buffer, acetate buffer, carbonate buffer) and applied potentials were tested to determine the optimal conditions for hydropyranone production. The progress of the reaction was monitored by HPLC to quantify the yields of hydropyranone and furfural. The robustness of the catalyst was assessed by performing multiple cycles of electrolysis. A flow electrolyzer was employed for gram-scale synthesis. For comparison, conventional chemical oxidation methods (using NBS and m-CPBA) were also conducted. The substrate scope was explored by testing various furfuryl alcohol derivatives with different substituents at the hydroxymethyl and 5'-positions. Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d) level were performed to understand the reaction mechanism. A mononuclear Ni model coordinated with a 2,2'-bipyridyl and two aqua ligands was used to model the active sites. DFT calculations explored two possible reaction pathways: one involving direct interaction between furfuryl alcohol and the Ni center and the other via oxygen-atom transfer. IR spectroscopy was also used to investigate the interaction between furfuryl alcohol and Ni-DVBP.

The researchers successfully synthesized a heterogenized nickel electrocatalyst (Ni-DVBP) via photo-induced polymerization of a bipyridyl ligand. This catalyst demonstrated high selectivity and yield (96%) for hydropyranone in the electrocatalytic Achmatowicz reaction, using water as both solvent and oxygen source, with a superior faradaic efficiency (84%, reaching 93% with 50 mM furfuryl alcohol). The catalyst exhibited remarkable robustness, with consistent high yields over multiple electrolysis cycles. Gram-scale synthesis using a flow electrolyzer achieved an 84% isolated yield. The electrocatalytic approach yielded comparable or better results than traditional chemical oxidation methods using NBS and m-CPBA. A wide range of furfuryl alcohol derivatives were successfully converted to their corresponding hydropyranones, demonstrating the versatility of the method. DFT calculations suggest that at low applied potentials, an intramolecular hydroxide transfer mechanism is favored, involving direct interaction between furfuryl alcohol and the nickel center. At higher potentials, an oxygen-atom transfer mechanism becomes more significant. The IR spectroscopic data supports the DFT results indicating that furfuryl alcohol is bound to the Ni center.

The results demonstrate a highly efficient and sustainable electrocatalytic strategy for the Achmatowicz reaction. This method addresses the limitations of previous chemical and electrochemical approaches by utilizing a robust, reusable catalyst, a green solvent (water), and avoiding toxic oxidants. The high selectivity for hydropyranone over furfural is a significant advantage. The mechanistic studies provide valuable insights into the reaction pathway, suggesting that the unsaturated coordination sphere of the nickel sites plays a critical role in facilitating the reaction at low applied potentials. The potential-dependent behavior highlights the importance of optimizing reaction conditions to maximize yield and selectivity. The success in synthesizing hydropyranones from various furfuryl alcohol derivatives, including those containing functional groups crucial for natural product synthesis, showcases the broad applicability of this method.

This study presents a highly efficient and sustainable electrocatalytic method for synthesizing hydropyranones from biomass-derived furfuryl alcohols. The use of a heterogenized nickel catalyst and water as both the solvent and oxygen source provides significant advantages over existing methods. The mechanistic understanding gained from DFT calculations and spectroscopic analysis further enhances the method's value. Future research could focus on exploring the application of this methodology to synthesize other valuable heterocyclic compounds and on developing even more efficient and scalable electrocatalytic systems.

While the electrocatalytic method demonstrated high efficiency and selectivity, the study focused primarily on furfuryl alcohol and its derivatives. Further investigation is needed to assess its applicability to a broader range of substrates. The DFT calculations, while providing valuable insights, are based on simplified models. More comprehensive computational studies could provide a deeper understanding of the reaction mechanism. Although the catalyst showed good robustness, long-term stability under continuous operation needs further evaluation for potential industrial applications.