Quasi-Catalytic Approach to N-Unprotected Lactams via Transfer Hydro-amination/Cyclization of Biobased Keto Acids

Levulinic acid (LA) and formic acid (FA) are concurrently derivable from biomass sugars, and recognized as sustainable feedstock for producing biofuels and chemicals. Herein, a benign and eco-friendly approach using low-cost formamide (FAM) and FA as nitrogen and hydrogen source, respectively, was developed to be highly efficient for the synthesis of 5-methyl-2-pyrrolidone (MPLD, up to 93% yield) from LA under quasi-catalytic and solvent-free conditions in a relatively short reaction time of 90 min at 160 degrees C. Deuterium-labeled and control experiments with 2D NMR illustrated the occurrence of transfer hydroamination process, where FA acted as an acid as well as H-donor. The smooth proceeding of the initial C-N bond formation process mainly contributed to the rapid substrate conversion, while the concurrent amidation process was favorable for the subsequent cyclization to give the desired lactam, as proved by computational calculations and kinetic studies. In addition, this quasi-catalytic system was applicable to the synthesis of various N-unprotected lactams in 76-95% yields from keto acids under benign conditions, and the target product could be simply isolated by extraction.