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

Abstract

The enantioselective α-amination of 1,3-dicarbonyl compounds has been performed using deep eutectic solvents (DES) as a reaction media and chiral 2-amino benzimidazole-derived compounds as a catalytic system. With this procedure, the use of toxic volatile organic compounds (VOCs) as reaction media is avoided. Furthermore, highly functionalized chiral molecules, which are important intermediates for the natural product synthesis, are synthetized by an efficient and stereoselective protocol. Moreover, the reaction can be done on a preparative scale, with the recycling of the catalytic system being possible for at least five consecutive reaction runs. This procedure represents a cheap, simple, clean, and scalable method that meets most of the principles to be considered a green and sustainable process.

Green Asymmetric Organocatalysis

“…Chiral 2‐aminobenzimidazole C51 efficiently promoted α‐amination of 1,3‐dicarbonyl compounds 98 with di‐ tert ‐butyl azodicarboxylate ( 99 ) as an electrophile in DES (Scheme ) . The reaction time was reduced from 4–5 h under classical conditions to 1 h under ultrasound irradiation.…”

Asymmetric Organocatalysis in Deep Eutectic Solvents

“…Thus, the electrophilic α‐amination of ethyl 2‐oxocyclopentane‐1‐carboxylate with di‐ tert ‐butylazodicarboxylate (10 mol%) was studied in different DESs such as ChCl/urea, ChCl/ethylene glycol and ChCl/tartaric acid amongst others, but gave the best results using ChCl/urea (1/2 molar ratio) and ChCl/gly (1/2 molar ratio) as a reaction media with up to 94 % conversion and a 75 % ee on average in the presence of a chiral 2‐aminobenzimidazole‐derived organocatalysts (10 mol%, Scheme 8). [23] The influence of the temperature in these reactions was also studied, achieving generally higher enantioselectivities when carrying out the reaction at 0 °C rather than the initial 25 °C. The reaction time could also be reduced from 5 to 1 h by carrying out the reaction using ultrasounds (360 W) at 25 °C.…”

Choline Chloride-Based DES as Solvents/Catalysts/Chemical Donors in Pharmaceutical Synthesis

“…Among the methods to gain access to this motif, significant developments have been reached in the asymmetric organocatalyzed amination of prochiral carbonyl compounds employing diazocarboxylates as nitrogen source [ 49 ]. Nigues et al have improved the sustainability of this reaction by using ChCl/glycerol and ChCl/urea as the solvents and 2-aminobenzimidazole derivatives as catalysts [ 50 ]. As depicted in Scheme 3 , the reaction of ethyl 2-oxocyclopentane-1-carboxylate with di- t -butyl-azodicarboxylate (DBAB) with a chiral 2-aminobenzimidazole derivative as catalyst under the optimized conditions gave the product of amination in excellent yield (94%) and good enantioselectivity (73% e.e.).…”