GLUCOSE-DERIVED IONIC LIQUIDS: EXPLORING LOW-COST SOURCES FOR NOVEL CHIRAL SOLVENTS

The exploration of Chiral Ionic Liquids (CILs) have expanded exponentially over the last five years, and the increasing number of new CILs published so far, displaying either chiral anion or chiral cation, gives good reason for the recent reviews reporting their synthesis and applications.1 CILs have been designed to act as stereoselective solvents in asymmetric synthesis, as chiral phase in gas chromatography, as shift reagents and chiral selectors in the determination of enantiomeric composition of pharmaceutical drugs. The synthesis of many CILs exploits the asymmetry already present in the chiral pool, especially in natural aminoacids or -hydroxy acids. However, no ILs based on natural carbohydrates have been reported so far. Carbohydrates are among the most abundant, low-cost natural sources of chiral material. Moreover, their manipulation has widely developed over more than one century, so that the protection and derivatization of natural monosaccharides can be easily performed through largely applied standard reactions. These considerations prompted us to design the synthesis and characterization of carbohydrate-based ionic liquids as new chiral solvents. Due to the presence of many hydroxyls, these CILs are provided of high coordination ability that can be tuned by varying the electronic density of their oxygens through a proper protecting group pattern. Therefore, carbohydrate-based ILs could be used as coordinating solvents in stereoselective and/or metal-catalysed reactions and, in principle, they could be used as shift reagents. We synthesized compounds 1-3 as the first carbohydrate-based ILs, starting from commercially available methyl--D-glucopyranoside. As these new CILs were supposed to act as solvents in organic reactions, they had to be stable in common reaction conditions. For this reason, the reactivity of hydroxyls was considerably lowered by protection as methyl ethers, and the labile anomeric acetal was reduced to an inert methylene group. ILs 1-3 were prepared following a common synthetic approach through a four-step procedure, and they were fully characterised in their physico-chemical properties. They represent the first terms of a new class of chiral solvents from low-cost natural sources.