Catalytic enantioselective reduction of nitroalkenes in DESs

The shift toward sustainable chemical processes that fulfill the principles of green chemistry, is recognized as a priority by the scientific community. In this context, one of the major culprits of waste production in chemical industries is the use of solvents, therefore the study of alternative and environmentally benign solvents is a topic that is gaining a steadily increasing attention. Deep Eutectic Solvents (DESs)1 are mixture of two or three components, typically derived from natural sources, which are capable of forming hydrogen bond interactions with each other, thus leading an eutectic mixture with a melting point lower than either of the individual components. DESs were firstly studied by Abbott2 and co-workers in 2003 and, since then, a considerable number of applications, spanning from metal processing to biodiesel purification, were published. The attention dedicated worldwide to DESs is linked to their unique features, to be easily prepared without the need of further purification, to be non-volatile, non-flammable and biodegradable. In 2016, our research group3 disclosed the possibility to run stereoselective reactions catalyzed by a chiral primary amine in bio-based eutectic mixtures. In particular, three different activation mode based on covalent interaction between the catalysts and the substrate were studied. Herein, we report our efforts for the development of the first organocatalytic reduction involving hydrogen bonding interactions among the substrate, the reagent and the catalyst in deep eutectic solvents which are made in turn of hydrogen bonds. We optimized the reduction of β,β-disubstituted nitroalkenes with Hantzsch ester (di-tert-butyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate) in the presence of thiourea-based chiral bifunctional catalysts to promote the formation of enantioenriched β-branched nitroalkanes, that was published by List4 and co-workers, employing DESs as reaction medium instead of traditional organic solvents. Several DESs were tested, obtaining the best results with a mixture of choline chloride and glycerol. The reduction protocol involves milder reaction conditions and shorter reaction time with the respect to the original publication and opens the way to the possibility of recycling the DES.