One-Pot Production of Cinnamonitriles from Lignin β-O-4 Segments Induced by Selective Oxidation of the γ-OH Group

The construction of N-containing aromatic compounds from lignin is of great importance to expanding the boundary of the biorefinery and meeting the demand for value-added biorefinery. However, it remains a huge challenge due to the complex lignin structure and the incompatible catalysis for C-O/C-C bond cleavage and C-N formation. Herein, sustainable synthesis of cinnamonitrile derivatives from lignin β-O-4 model compounds in the presence of 2,2,6,6-tetramethylpiperidine oxide (TEMPO), (diacetoxyiodo)benzene (BAIB), and a strong base has been achieved in a one-pot, two-step fashion under transition-metal-free conditions. Mechanistic studies suggest that this transformation starts from selective oxidation of C_γ-OH of the β-O-4 model compound, followed by retro-aldol condensation, resulting in the cleavage of the C_α-C_β bond to afford veratraldehyde. Whereafter, the aldol condensation reaction allows coupling of veratraldehyde with nitriles to provide cinnamonitriles. With this protocol, 3,4-dimethoxycinnamonitrile and 3,4-dimethoxyphenyl-2-phenylacrylonitrile were synthesized from lignin β-O-4 model compounds and showed good antibacterial or antifungal activity, showcasing the application potential of lignin in pharmaceutical synthesis.