Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators

Abstract

In organic chemistry ionic liquids (ILs) have emerged as safe and recyclable reaction solvents. In the presence of a base ILs can be deprotonated to form catalytically active N-Heterocyclic Carbenes (NHCs). Here we have used ILs as precatalysts in the addition of α,β-unsaturated aldehydes to chalcones to form 1,6-ketoesters, incorporating an anti-diphenyl moiety in a highly stereoselective fashion. The reaction has a broad substrate scope and several functional groups and heteroaromatics can be integrated into the ketoester backbone in generally good yields with maintained stereoselectivity. The reaction protocol is robust and scalable. The starting materials are inexpensive and the products can be obtained after simple filtration, avoiding solvent-demanding chromatography. Furthermore, the IL can be recycled up to 5 times without any loss of reactivity. Moreover, the 1,6-ketoester end product is a potent gelator in several hydrocarbon based solvents. The method enables rapid access to and evaluation of a new class of low molecular weight gelators (LMWGs) from recyclable and inexpensive starting materials.

Reactions of Sulfur-Containing Organic Compounds and Peptides in 1-Ethyl-3-methyl-imidazolium Acetate

“…The process of imidazol-2-ylidene formation in imidazolium-based ILs is reported to occur by a simple deprotonation of the carbon atom in-between the two nitrogens of the imidazolium ring. ,, For 1,3-dialkyl-substituted imidazolium ILs Hollóczki et al reported that the equilibrium between the ion pair and the corresponding hydrogen-bonded complex of the free acid and NHC can be shifted toward NHC formation in the presence of the relatively basic anion of the IL …”

“…32 The process of imidazol-2-ylidene formation in imidazoliumbased ILs is reported to occur by a simple deprotonation of the carbon atom in-between the two nitrogens of the imidazolium ring. 24,25,33 For 1,3-dialkyl-substituted imidazolium ILs Holloćzki et al reported that the equilibrium between the ion pair and the corresponding hydrogen-bonded complex of the free acid and NHC can be shifted toward NHC formation in the presence of the relatively basic anion of the IL. 24 The hypothesis about the presence of trace amounts of highly reactive carbenes in the neat ILs with relatively basic anions might pave the way for a general facile use of in situ formed NHCs in catalytic reactions.…”

Ionic Liquids as Carbene Catalyst Precursors in the One-Pot Four-Component Assembly of Oxo Triphenylhexanoates (OTHOs)

“…Recently, we reported the use of EMIMAc as a precatalyst in the formal Michael addition of α,β-unsaturated aldehydes to chalcones in the synthesis of oxo triphenylhexanoates (OTHOs) [40,41]. In this study it was also shown that one of the OTHOs was a potent low-molecular-weight gelator in hydrocarbon-based solvents.…”