Selective Conversion of Malononitrile and Unprotected Carbohydrates to Bicyclic Polyhydroxyalkyl Dihydrofurans Using Magnesium Oxide as a Recyclable Catalyst

Abstract

Using renewable feedstocks to access highly functionalized molecules in a concise manner is a promising approach to sustainable syntheses. Previous studies used malononitrile to convert simple sugars to polyhydroxylalkyl aminofurans in the presence of various catalysts. Herein, a chemodivergent method is disclosed for the reaction of the same unprotected sugars with malononitrile to instead form bicyclic 2,3-dihydrofuran products in yields up to 85% with good regioselectivities. Kinetic, NMR, and computational studies support a proposed mechanism for the formation of dihydrofuran products. By employing a mild set of reaction conditions (aqueous solvent, at room temperature, in under 4 h) and a recyclable heterogeneous MgO catalyst, this method serves as a powerful tool for carbohydrate upcycling that offers useful and interesting nonaromatic products.

Kinetic and Mechanistic Study of Aldose Conversion to Functionalized Furans in Aqueous Solutions

“…As an alternative to the direct conversion of carbohydrates as sole reactants, strategies based on the use of reactant mixtures for the upgrading of aldoses have been devised [33]. Reactions of the carbohydrate backbone with CH acidic nucleophilic compounds have shown promise in the formation of various substance classes, including C-glycosidic ketones, oligomeric cyclic compounds, and polyfunctional furfural derivatives [34][35][36][37][38][39][40][41]. These reactions are mainly catalyzed by either Lewis acids or Brønsted bases in either aqueous solutions or alcohols and can lead to important heterocyclic precursors, including enzyme inhibitors, pharmaceuticals, and fine chemicals [38].…”

“…Special emphasis is placed on the mild conversion of glucose and xylose with malononitrile to a trisubstituted furanic derivative bearing amino, nitrile, and polyol functionality. This reaction has recently attracted significant attention [36,38]. Proposed mechanisms initially included reactions to compound 3 of Scheme 1 in competition to aromatization to 4 [38].…”

“…Proposed mechanisms initially included reactions to compound 3 of Scheme 1 in competition to aromatization to 4 [38]. Alternatively, previous DFT calculations suggested a pathway that proceeded through ketenimine intermediates [36]. The formation of the intermediate 2 was not considered.…”

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

“…Traditional Knoevenagel reactions often rely on catalysts such as aniline, piperidine and triethylamine [ 24 , 27 , 28 ], whose use is undesirable due to toxicity and environmental concerns. Nontoxic, robust and cheap catalysts sourced from nature are clearly preferred by chemical and pharmaceutical industries to comply with environmental requirements [ 29 ]. Such catalysts can ideally provide reusability and ease of separation.…”

“…pharmaceutical industries to comply with environmental requirements [29]. Such catalysts can ideally provide reusability and ease of separation.…”