Chiral Lewis acid

Chiral Lewis acids (CLAs) are a type of Lewis acid catalyst that effects the chirality of the substrate as it reacts with it. In such reactions the synthesis favors the formation of a specific enantiomer or diastereomer. The method then is an enantioselective asymmetric synthesis reaction. Since they affect chirality, they produce optically active products from optically inactive or mixed starting materials. This type of preferential formation of one enantiomer or diastereomer over the other is formally known as an asymmetric induction. In this kind of Lewis acid. the electron-accepting atom is typically a metal, such as indium, zinc, lithium, aluminium, titanium, or boron. The chiral-altering ligands employed for synthesizing these acids most often have multiple Lewis basic sites (often a diol or a dinitrogen structure) that allow the formation of a ring structure involving the metal atom. Chiral Lewis acids (CLAs) are a type of Lewis acid catalyst that effects the chirality of the substrate as it reacts with it. In such reactions the synthesis favors the formation of a specific enantiomer or diastereomer. The method then is an enantioselective asymmetric synthesis reaction. Since they affect chirality, they produce optically active products from optically inactive or mixed starting materials. This type of preferential formation of one enantiomer or diastereomer over the other is formally known as an asymmetric induction. In this kind of Lewis acid. the electron-accepting atom is typically a metal, such as indium, zinc, lithium, aluminium, titanium, or boron. The chiral-altering ligands employed for synthesizing these acids most often have multiple Lewis basic sites (often a diol or a dinitrogen structure) that allow the formation of a ring structure involving the metal atom. Achiral Lewis acids have been used for decades to promote the synthesis of racemic mixtures in a myriad different reactions. Starting in the 1960s chemists have use the chiral acids to induce the enantioselective reactions. Common reaction types include Diels-Alder reactions, the ene reaction, cycloaddition reactions, hydrocyanation of aldehydes, and most notably, Sharpless expoxidations. The enantioselectivity of CLAs derives from their ability to perturb the free energy barrier along the reaction coordinate pathway that leads to either the R- or S- enantiomer. Ground state diastereomers and enantiomers are of equal energy in the ground state, and when reacted with an achiral lewis acid, their diastereomeric intermediates, transition states, and products are also of equal energy. This leads to the production of racemic mixtures of products. However, when a CLA is used in the same reaction, the energetic barrier of formation of one diastereomer is less than that of another – the reaction is under kinetic control. If the difference in the energy barriers between the diastereomeric transition states are of sufficient magnitude, then a high enantiomeric excess of one isomer should be observed (Figure 2). Diels-Alder reactions occur between a conjugated diene and an alkene (commonly known as the dienophile). This cycloaddition process allows for the stereoselective formation of cyclohexene rings capable of possessing as many as four contiguous stereogenic centers. Diels-Alder reactions can lead to formation of a variety of structural isomers and stereoisomers. The molecular orbital theory considers that endo transition state, instead of the exo transition state, is favored (endo addition rule). Also, augmented secondary orbital interactions have been postulated as the source of enhanced endo diastereoselection.