Abstract

2-methyltetrahydrofuran (2-MeTHF) has become a broadly used (biogenic) solvent in organic synthesis, particularly with promising applications in biocatalysis, due to its excellent behaviour and favourable properties. 2-MeTHF may be derived from renewable sources - such as furfural or levulinic acid and its low water solubility facilitates its complete recovery in reactions in aqueous media, reducing wastes and simplifying the recycling and reuse. 2-MeTHF properties typically outperform those of traditional solvents (such as THF), enabling its application in a wide range of chemical and enzymatic synthetic processes. Remarkably, this trend can be observed not only in academia, but also at industrial scale, where companies start to assess 2-MeTHF for the replacement of non-GRAS solvents (Generally Regarded As Safe). Given that increasing importance, this mini-review discusses the recent advances in biocatalysis using 2-MeTHF, with applications for different enzymes (hydrolases, oxidoreductases, lyases, etc.), as well as in innovative combinations such as gas-liquid mixtures (CO2-2-MeTHF expanded phase), in multi-step enzymatic systems, and flow biocatalysis. The combination of 2-MeTHF with the intrinsic sustainability associated with biotransformations creates an attractive synergy.

Keywords: 2-methyltetrahydrofuran, biogenic solvents, biocatalysis, biotransformations, green chemistry, API.

Graphical Abstract