One-Pot Production\nof Cinnamonitriles from Lignin\nβ‑O‑4 Segments Induced by Selective Oxidation\nof the γ‑OH Group

The construction of N-containing aromatic compounds from\nlignin\nis of great importance to expanding the boundary of the biorefinery\nand meeting the demand for value-added biorefinery. However, it remains\na huge challenge due to the complex lignin structure and the incompatible\ncatalysis for C–O/C–C bond cleavage and C–N formation.\nHerein, sustainable synthesis of cinnamonitrile derivatives from lignin\nβ-O-4 model compounds in the presence of 2,2,6,6-tetramethylpiperidine\noxide (TEMPO), (diacetoxyiodo)benzene (BAIB), and a strong base has\nbeen achieved in a one-pot, two-step fashion under transition-metal-free\nconditions. Mechanistic studies suggest that this transformation starts\nfrom selective oxidation of C<sub>γ</sub>-OH of the β-O-4\nmodel compound, followed by retro-aldol condensation, resulting in\nthe cleavage of the C<sub>α</sub>–C<sub>β</sub> bond to afford veratraldehyde. Whereafter, the aldol condensation\nreaction allows coupling of veratraldehyde with nitriles to provide\ncinnamonitriles. With this protocol, 3,4-dimethoxycinnamonitrile and\n3,4-dimethoxyphenyl-2-phenylacrylonitrile were synthesized from lignin\nβ-O-4 model compounds and showed good antibacterial or antifungal\nactivity, showcasing the application potential of lignin in pharmaceutical\nsynthesis.