Tailoring the Formation of Functionalized Furans from Glucose in Water with Nature-Sourced Catalysts and In Situ NMR

Abstract

Chain elongation of unprotected carbohydrates in water under mild conditions remains a challenge both in chemical and biochemical synthesis. The Knoevenagel addition or condensation enables transformations to bioactive scaffolds for pharmaceutical and agrochemical compounds. Unfortunately, the catalysts in use for these transformations often reduce the green metrics of the transformations. Here, we use in situ NMR visualizations to explore the prospective use of natural catalysts for the synthesis of triple- and quadruple-functionalized furan- or dihydrofuran-derivatives from glucose and malononitrile. The dihydrofuran derivatives are formed as kinetic, major intermediates in the pathway to furan derivatives when using naturally abundant MgO or bio-sourced chitosan and N-Methyl-d-glucamine (meglumine) as the catalysts in water. Both catalyst loading, solvent composition and pH can be adapted to populate dihydrofurans with four substituents by slowing down their further reactions. Higher temperatures and higher pH values favor the formation of triple-functionalized furans over quadruple-substituted dihydrofurans, which may be bicyclic or monocyclic. Compared to more traditional catalysts, nature-sourced options offer more sustainable options that emulate natural processes. Visualization with in situ NMR contributes to streamlining the development of cheap and environmentally benign procedures for carbohydrate chain elongation.