Enantioselective Biginelli Reaction Catalyzed by (L)-Prolinamide Containing Imidazolium Ionic Liquid

(L)-Prolinamide containing imidazolium ionic liquids have been synthesized and evaluated as organocatalysts for the asymmetric Biginelli reaction of benzaldehydes, urea, and beta-keto esters. The synthesized chiral ionic liquids were characterized by various techniques such as FT-NMR, FT-IR, TGA, and HRMS. The chiral ionic liquid containing adamantyl (L)-prolinamide having [BF4](-) anion (5 mol %) and p-toluenesulfonic acid (5 mol %) as an additive catalyzed the Biginelli reaction and afforded a variety of chiral 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs) in 16-74 % yields and 7-85 % ee's after 48 h at room temperature and out of 30 chiral DHPMs products, 18 are new. A plausible reaction mechanism and transition states or intermediates have been proposed and supported by FT-NMR spectroscopy and DFT calculations. The asymmetric induction was favored by the Re-face attack on the imine bond and the Biginelli products were obtained with (R)-absolute configuration. The DFT calculations (B3LYP/631-G*) were performed to find the energy of the intermediates.

Automated summary

In this study, prolinamide containing imidazolium ionic liquids were synthesized and evaluated as organocatalysts for the asymmetric Biginelli reaction. The synthesized chiral ionic liquids were characterized and one particular catalyst was found to efficiently catalyze the reaction at room temperature, resulting in a variety of chiral products.