Chiral Ionic Liquids Based on L-Cysteine Derivatives for Asymmetric Aldol Reaction

Structure, and consequently properties, of ionic liquids can be easily tailored by changing cation/anion combinations and/or attaching functional groups. By grafting enantiopure moieties to the framework of ionic liquid it is possible to prepare bioinspired chiral molecules that can serve as a reaction medium, additive or even asymmetric catalyst. In this context, new chiral ionic liquids (CILs), based on biomolecules, such as aminoacids (L-cysteine derivatives), have been synthesised and tested in asymmetric aldol condensation of aldehydes and ketones. The best results were obtained for CILs composed of S-methyl-L-cysteine cation and bis(trifluoromethane)sulfonimide anion, in the reaction of 2- or 4-nitrobenzaldehyde with acetone or cyclohexanone, giving the aldol product in moderate yields 70–76% and high ee values (up to 96%).

NMR relaxation time measurements of solvent effects in an organocatalysed asymmetric aldol reaction over silica SBA-15 supported proline

Immobilisation of organocatalysts onto solid supports represents a very promising solution to tackle their low productivity by enabling their reuse. Herein, the use of NMR relaxation measurements, coupled with reaction...

Asymmetric Aldol Reaction of Alkenyl Esters with α-Ketoesters Catalyzed by Chiral Tin Alkoxides

A catalytic enantioselective aldol reaction of alkenyl esters with α-ketoesters was achieved using an (R)-BINOL-derived chiral tin dibromide possessing a 4-t-butylphenyl group at 3- and 3’-positions as the chiral precatalyst in the presence of sodium methoxide and methanol. Optically active aldol products possessing a chiral tertiary carbon with up to 92% ee were diastereoselectively obtained in moderate to high yields not only from cyclic alkenyl esters but also from acyclic ones under the influence of the in situ generated chiral tin methoxide.

Siloxy Esters as Traceless Activator of Carboxylic Acids: Boron-Catalyzed Chemoselective Asymmetric Aldol Reaction

The catalytic asymmetric aldol reaction of carboxylic acids is among the most useful reactions for the synthesis of biologically active compounds and pharmaceuticals. Despite the existence of many prominent reports, no general method is available to incorporate the aldol motif into complex carboxylic acids and their derivatives at late stages. Chemoselective catalytic asymmetric aldol reaction of multifunctional carboxylic acids is difficult to achieve, due to the high basicity required for enolization and the poisonous chelation of β-hydroxy acid products to Lewis acid catalysts. Herein, we identified that preconversion of carboxylic acids to siloxy esters facilitated the boron-catalyzed direct aldol reaction, leading to the development of carboxylic acid-selective, catalytic asymmetric aldol reaction applicable to multifunctional substrates. The asymmetric boron catalyst stereodivergently controlled the products’ stereochemistry depending on the catalyst’s chirality, not on the stereochemical bias of substrates. Computational studies rationalized the mechanism of the catalytic cycle and the stereoselectivity, and proposed Si/B enediolates as the active species for the asymmetric aldol reaction. The silyl ester formation facilitated both enolization and catalyst turnover through acidifying the α-proton of substrates and attenuating poisonous Lewis bases to the boron catalyst.

Siloxy Esters as Traceless Activator of Carboxylic Acids: Boron-Catalyzed Chemoselective Asymmetric Aldol Reaction

The catalytic asymmetric aldol reaction of carboxylic acids is among the most useful reactions for the synthesis of biologically active compounds and pharmaceuticals. Despite the existence of many prominent reports, no general method is available to incorporate the aldol motif into complex carboxylic acids and their derivatives at late stages. Chemoselective catalytic asymmetric aldol reaction of multifunctional carboxylic acids is difficult to achieve, due to the high basicity required for enolization and the poisonous chelation of β-hydroxy acid products to Lewis acid catalysts. Herein, we identified that preconversion of carboxylic acids to siloxy esters facilitated the boron-catalyzed direct aldol reaction, leading to the development of carboxylic acid-selective, catalytic asymmetric aldol reaction applicable to multifunctional substrates. The asymmetric boron catalyst stereodivergently controlled the products’ stereochemistry depending on the catalyst’s chirality, not on the stereochemical bias of substrates. Computational studies rationalized the mechanism of the catalytic cycle and the stereoselectivity, and proposed Si/B enediolates as the active species for the asymmetric aldol reaction. The silyl ester formation facilitated both enolization and catalyst turnover through acidifying the α-proton of substrates and attenuating poisonous Lewis bases to the boron catalyst.