Chiral Lewis acid

In this kind of Lewis acid, the electron-accepting atom is typically a metal, such as indium, zinc, lithium, aluminium, titanium, or boron.

[1][2] Achiral Lewis acids have been used for decades to promote the synthesis of racemic mixtures in myriad different reactions.

[3] The enantioselectivity of CLAs derives from their ability to perturb the free energy barrier along with the reaction coordinate pathway that leads to either the R- or S- enantiomer.

If the difference in the energy barriers between the diastereomeric transition states are of sufficient magnitude, then a high enantiomeric excess of one isomer is observed.

A typical CLA catalyst is derived from a Mg2+ center made chiral by attachment of a binol- phosphate ester.

[5] A complex derived from diethylaluminium chloride and a “vaulted” biaryl ligand below catalyzes the enantioselective Diels–Alder reaction between cyclopentadiene and methacrolein.

Pi stacking between the aryl group and aldehyde has been suggested as an organizational feature that imparts high enantioselectivity to the cycloaddition.

Bronsted acid-assisted chiral Lewis acid (BLA) catalyzes a number of diene-aldehyde cycloaddition reactions.

The Baylis–Hillman reaction is a route for C-C bond formation between an alpha, beta-unsaturated carbonyl and an aldehyde, which requires a nucleophilic catalyst, usually a tertiary amine, for a Michael-type addition and elimination.

The enantioselectivity is believed to be due to the steric interactions between the methyl and phenyl group, which makes the transition structure of the iso product considerably more favorable.