Photoredox and Vanadate Cocatalyzed Hydrolysis of Aryl Ethers for Efficient C−O Bond Cleavage at Ambient Temperature

Aryl ethers, comprising aryl alkyl ethers and diaryl ethers, are prevalent in lignin, a major biomass component, and are extensively utilized in organic synthesis as protective groups for phenolic hydroxyls. Traditional methods for C−O bond cleavage in aryl ethers often require harsh conditions due to the high bond dissociation energy, thus limiting their application in sustainable and gentle processes. Recent advances have focused on hydrogenolysis and hydrolysis, but these often involve over-stoichiometric reagents or elevated temperatures, which are not ideal from a sustainability perspective.

A new study published in ACS Catalysis led by Professor Yang Li and conducted by Rong-Gui Hu, Yueqian Sang, Fang-Fang Tan, Yuan-Li Sun, and from the Xi’an Jiaotong University together with Professor Xiao-Song Xue from Shanghai Institute of Organic Chemistry, the University of Chinese Academy of Sciences developed a new methodology for the hydrolysis of aryl ethers through photoredox and vanadate cocatalysis. Their goal was to achieve efficient and selective cleavage of C−O bonds at ambient temperatures, with a broad substrate scope and high atom economy.  The team first explored the hydrolysis of diphenyl ether (DPE) as a model substrate in a mixture of acetonitrile (CH₃CN) and water, using an acridinium photocatalyst under blue LED irradiation. They experimented with different vanadium sources and bases, identifying V₂O₅ and tetrabutylammonium hydroxide (TBAH) as the optimal catalytic system. They optimized the reaction conditions by varying the amount of V₂O₅, the choice of base, and the solvent system. The optimized conditions involved 10 mol% V₂O₅, 20 mol% TBAH, under blue LED light at room temperature. The authors subjected a broad range of phenyl ethers, including aryl alkyl ethers and diaryl ethers to the optimized reaction conditions and tested the new method’s efficiency across various substrates, including those with sensitive functional groups and different lignin model compounds. The researchers specifically tested substrates that mimic the structural elements of lignin (e.g., α-O-4, β-O-4, and 4-O-5 linkages), to evaluate the potential of their method for lignin depolymerization.

To understand the underlying reaction mechanism, they conducted experiments using isotopically labeled water, radical scavengers, and electron paramagnetic resonance (EPR) spectroscopy. They also explored the nucleophilicity of water towards radical cations, the role of the “hydroxyl shuttle” in facilitating nucleophilic aromatic substitution, and the involvement of noncovalent interactions between the aryl ether radical cation and vanadate. The team successfully developed a method for the hydrolysis of various aryl ethers, demonstrating high efficiency (up to 95% yield) and selectivity under ambient conditions. This method avoided the need for harsh conditions, over-stoichiometric base/acid, and external hydrogen sources. Moreover, the optimized reaction conditions were applicable to a wide range of substrates, including aryl alkyl ethers and diaryl ethers. This includes challenging substrates that are relevant to lignin structures, showcasing the potential of this method for biomass valorization. Furthermore, the experiments with isotopically labeled water confirmed that the hydrolysis pathway involves the cleavage of the C(sp2)−O bond exclusively. The authors’ findings suggested that a vanadate derived from in situ hydrolysis of V₂O₅ acted as an efficient catalyst for the hydrolysis of an aryl ether radical cation. This was facilitated by a “hydroxyl shuttle” mechanism, where the vanadate serves to link water molecules to the aryl ether radical cations, enhancing the nucleophilicity of water. Noncovalent interactions between the aryl ether radical cation and the in situ generated vanadate were crucial for triggering the nucleophilic attack, leading to the cleavage of the C−O bond.

The “hydroxyl shuttle” concept presents a versatile tool for nucleophilic aromatic substitution reactions, potentially extending beyond C−O bond cleavage to other types of bond transformations. Furthermore, the approach aligns with principles of green chemistry, emphasizing the need for processes that are efficient, selective, and have minimal environmental impact. In conclusion, the innovative method demonstrated significant potential for the depolymerization of lignin, with successful cleavage of C−O bonds in various lignin model compounds. This represents a significant step towards the utilization of lignin as a renewable resource for the production of valuable aryl chemicals.