Production of alkylpyrimidines from lignin β-O-4 model compounds induced by Rh-catalyzed unconventional dehydrogenation

The sustainable production of N-heterocyclic compounds from renewable lignin is of significance to increasing the economic feasibility of biorefineries and alleviating fossil-chain dependencies in the pharmaceutical industry. However, mild cleavage of C_β–O bond of lignin β-O-4 model compounds to release reactive monomers (such as acetophenone, phenol) is still a challenge, and current protocols are limited to the employment of aromatic alcohols as a co-substrate to construct lignin-derived N-heterocyclics. In this article, a relay and synergistic catalysis between rhodium-terpyridine and NaOH was developed to induce unconventional dehydrogenation for the efficient synthesis of alkylpyrimidines from lignin β-O-4 model compounds reacting with aliphatic alcohol and amidines in a one-pot fashion. Mechanism study indicated an unconventional dehydrogenation that promoted the efficient cleavage of C_β–O bond and dehydrogenation of alcohol, viz. the replacement of rhodium catalyst on the hydrogen of C_α-OH promotes the elimination of acidic C_α-H, which can weaken C_β-O bond and lead to the cleavage of the β-O-4 linkage to afford acetophenone intermediate, a similar replacement effect was accomplished in the dehydrogenation of alcohol to give another key intermediate aliphatic aldehyde simultaneously. These two intermediates then reacted with amidine to provide alkylpyrimidine in yield up to 90%. With this protocol, a wide range of functionalized alkylpyrimidines and aromatic pyrimidines are synthesized from lignin β-O-4 model compounds. This work overcomes the substrate's limitation and showcases the application of the strategy in sustainable synthesis of biobased N-containing heterocyclic compounds.