Mechanistic Investigations into the Catalytic Levulinic Acid Hydrogenation, Insight in H/D Exchange Pathways, and a Synthetic Route to d₈-?-Valerolactone

?-Valerolactone (GVL) is readily accessible by catalytic hydrogenation of carbohydrate-derived levulinic acid (LA) and is an attractive biobased chemical with a wide range of applications in both the chemical (e.g., as biomass-derived solvent) and the transportation fuel sector. In this study, we used isotopic labeling experiments to provide insights into the catalytic hydrogenation pathways involved in the conversion of LA to GVL under different reaction conditions using water as an environmentally benign solvent and Ru/C as a readily available catalyst. 2H NMR experiments combined with quantum chemical calculations revealed that deuterium atoms can be incorporated at different positions as well as the involvement of the different intermediates 4-hydroxypentanoic acid and α-angelica lactone (α-AL). The insight provided by these studies revealed an as of yet unexploited sequential deuteration route to synthesize fully deuterated LA and GVL. The route starts by the conversion of LA to α-AL followed by a selective deuteration of the acidic protons of α-AL by H/D exchange with D2O. Subsequent ring-opening in D2O (d2-AL to d3-LA) and exchange of the remaining protons of d3-LA via a keto-enol tautomerization by heating in D2O under acidic conditions gives d8-LA. Finally, the d8-LA is catalytically reduced at low temperature using Ru/C with D2 in D2O to d8-GVL.