Chiral 2-Aminobenzimidazoles in Deep Eutectic Mixtures: Recyclable Organocatalysts for the Enantioselective Michael Addition of 1,3-Dicarbonyl Compounds to β-Nitroalkenes

Abstract

A catalytic system based on deep eutectic solvents and chiral 2-amino benzimidazole organocatalysts is used to promote the enantioselective addition of 1,3-dicarbonyl compounds to β-nitrostyrenes. This procedure avoids the use of toxic VOC as reaction medium, providing access to highly functionalized chiral molecules in a selective and efficient manner. Furthermore, the reaction can be performed on a large scale and the recyclability of the catalytic system is possible at least for four times, leading to a clean, cheap, simple and scalable procedure that meets most of the criteria required to be a green and sustainable process. NMR studies have Page 1 of 23 ACS Paragon Plus Environment ACS Sustainable Chemistry & Engineering 2 confirmed the key role of the hydrogen-bonding interactions between the DES and the chiral organocatalyst, which allow their recovery and the recyclability of the system.

Deep Eutectic Mixtures as Reaction Media for the Enantioselective Organocatalyzed α-Amination of 1,3-Dicarbonyl Compounds

“…As shown in Table 1, entries 12 and 13, under these conditions compound 4 was obtained with similar enantioselectivities with only a small erosion of the reaction conversion. For asymmetric organocatalyzed processes, the use of DES as a reaction medium has been barely studied, with the aldol reaction [30][31][32][33][34] and conjugated addition [13,29,35] being the main focus. For these processes a rational design of the organocatalyst and the right choice of the DES has shown to be critical to obtain good results and allow organocatalyst recycling.…”

“…Our research group has established the practicality of bifunctional chiral 2-aminobenzimidazole derivatives [20,21] 1 and 3 (Scheme 1) as efficient organocatalysts in the asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroolefins [22] and maleimides [23,24] as well as in the αfunctionalization [25][26][27][28] of these interesting nucleophiles using volatile organic solvents (VOCs) as a reaction medium. More fascinating, we have also demonstrated that the catalytic system based on the deep eutectic solvent choline chloride/glycerol and chiral 2-aminobenzimidazole organocatalysts 2 efficiently promotes the enantioselective addition of 1,3-dicarbonyl compounds to β-nitrostyrenes, avoiding the use of toxic VOC as reaction media [29].…”

Enantioselective One-Pot Synthesis of Biaryl-Substituted Amines by Combining Palladium and Enzyme Catalysis in Deep Eutectic Solvents

“…Compared to the related ionic liquids (ILs), DESs are cheaper, easier to make, tunable, highly biodegradable, virtually non-toxic and do not require further purification. As illustrated by the exponential growth of literature, DES technology has been applied to a wide-ranging area of research topics such as organic synthesis, 31,32 metal-catalysis [33][34][35][36] and organocatalysis, [37][38][39][40] energy technology, 41,42 material chemistry, 43 or separation processes. 44 In biocatalysis, since the 2008 proof-of-concept, 45 many examples have showcased ad hoc protocols for biotransformations in DESs and DES-buffer mixtures.…”

Enantioselective Organocatalyzed a-Amination of 1,3-Dicarbonyl Compounds in Deep Eutectic Mixtures

“…The use of DES as a reaction medium for asymmetric organocatalyzed processes has been barely studied being the aldol reaction [30][31][32][33][34] and conjugated additions [13,29,35] the main targets with the choice of the DES and design of the organocatalyst shown to be crucial to achieve good results and enable the organocatalyst recycling.…”

“…Our research group has demonstrated the practicality of bifunctional chiral 2aminobenzimidazole derivatives [20,21] 1 and 3 (Scheme 1) as efficient organocatalysts in the asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroolefins [22] and maleimides [23,24] as well as in the -functionalization [25][26][27][28] of these interesting nucleophiles using volatile organic solvents (VOCs) as reaction medium. More fascinating, we have also demonstrated that the catalytic system based on the deep eutectic solvent choline chloride/glycerol and chiral 2aminobenzimidazole organocatalysts 2 efficiently promotes the enantioselective addition of 1,3dicarbonyl compounds to β-nitrostyrenes, avoiding the use of toxic VOC as reaction medium [29].…”