Community hub
Recent from talks
Knowledge base stats:
Talk channels stats:
Members stats:
Lewis acid catalysis
In organic chemistry, Lewis acid catalysis is the use of metal-based Lewis acids as catalysts for organic reactions. The acids act as an electron pair acceptor to increase the reactivity of a substrate. Common Lewis acid catalysts are based on main group metals such as aluminum, boron, silicon, and tin, as well as many early (titanium, zirconium) and late (iron, copper, zinc) d-block metals. The metal atom forms an adduct with a lone-pair bearing electronegative atom in the substrate, such as oxygen (both sp2 or sp3), nitrogen, sulfur, and halogens. The complexation has partial charge-transfer character and makes the lone-pair donor effectively more electronegative, activating the substrate toward nucleophilic attack, heterolytic bond cleavage, or cycloaddition with 1,3-dienes and 1,3-dipoles.
Many classical reactions involving carbon–carbon or carbon–heteroatom bond formation can be catalyzed by Lewis acids. Examples include the Friedel-Crafts reaction, the aldol reaction, and various pericyclic processes that proceed slowly at room temperature, such as the Diels-Alder reaction and the ene reaction. In addition to accelerating the reactions, Lewis acid catalysts are able to impose regioselectivity and stereoselectivity in many cases.
Early developments in Lewis acid reagents focused on easily available compounds such as TiCl4, BF3, SnCl4, and AlCl3. Over the years, versatile catalysts bearing ligands designed for specific applications have facilitated improvement in both reactivity and selectivity of Lewis acid-catalyzed reactions. More recently, Lewis acid catalysts with chiral ligands have become an important class of tools for asymmetric catalysis.
Challenges in the development of Lewis acid catalysis include inefficient catalyst turnover (caused by catalyst affinity for the product) and the frequent requirement of two-point binding for stereoselectivity, which often necessitates the use of auxiliary groups.
In reactions with polar mechanisms, Lewis acid catalysis often involves binding of the catalyst to Lewis basic heteroatoms and withdrawing electron density, which in turn facilitates heterolytic bond cleavage (in the case of Friedel-Crafts reaction) or directly activates the substrate toward nucleophilic attack (in the case of carbonyl addition reactions). The dichotomy can have important consequences in some reactions, as in the case of Lewis acid-promoted acetal substitution reactions, where the SN1 and SN2 mechanisms shown below may give different stereochemical outcomes. Studying the product ratio in a bicyclic system, Denmark and colleagues showed that both mechanisms could be operative depending on the denticity of the Lewis acid and the identity of the R' group.
In Diels-Alder and 1,3-dipolar cycloaddition reactions, Lewis acids lower the LUMO energy of the dienophile or dipolarophile, respectively, making it more reactive toward the diene or the dipole.
Among the types of reactions that can be catalyzed by Lewis acids, those with carbonyl-containing substrates have received the greatest amount of attention. The first major discovery in this area was in 1960, when Yates and Eaton reported the significant acceleration of the Diels-Alder reaction by AlCl3 when maleic anhydride is the dienophile.
Early theoretical studies that depended on frontier orbital analysis established that Lewis acid catalysis operates via lowering of the dienophile's LUMO energy. Recent studies, however, have shown that this rationale behind Lewis acid-catalyzed Diels-Alder reactions is incorrect. It is found that Lewis acids accelerate the Diels-Alder reaction by reducing the destabilizing steric Pauli repulsion between the interacting diene and dienophile and not by lowering the energy of the dienophile's LUMO and consequently, enhancing the normal electron demand orbital interaction. The Lewis acid bind via a donor-acceptor interaction to the dienophile and via that mechanism polarizes occupied orbital density away from the reactive C=C double bond of the dienophile towards the Lewis acid. This reduced occupied orbital density on C=C double bond of the dienophile will, in turn, engage in a less repulsive closed-shell-closed-shell orbital interaction with the incoming diene, reducing the destabilizing steric Pauli repulsion and hence lowers the Diels-Alder reaction barrier. In addition, the Lewis acid catalyst also increases the asynchronicity of the Diels-Alder reaction, making the occupied π-orbital located on the C=C double bond of the dienophile asymmetric. As a result, this enhanced asynchronicity leads to an extra reduction of the destabilizing steric Pauli repulsion as well as a diminishing pressure on the reactants to deform, in other words, it reduced the destabilizing activation strain (also known as distortion energy). This working catalytic mechanism is known as Pauli-lowering catalysis, which is operative in a variety of organic reactions.
Hub AI
Lewis acid catalysis AI simulator
(@Lewis acid catalysis_simulator)
Lewis acid catalysis
In organic chemistry, Lewis acid catalysis is the use of metal-based Lewis acids as catalysts for organic reactions. The acids act as an electron pair acceptor to increase the reactivity of a substrate. Common Lewis acid catalysts are based on main group metals such as aluminum, boron, silicon, and tin, as well as many early (titanium, zirconium) and late (iron, copper, zinc) d-block metals. The metal atom forms an adduct with a lone-pair bearing electronegative atom in the substrate, such as oxygen (both sp2 or sp3), nitrogen, sulfur, and halogens. The complexation has partial charge-transfer character and makes the lone-pair donor effectively more electronegative, activating the substrate toward nucleophilic attack, heterolytic bond cleavage, or cycloaddition with 1,3-dienes and 1,3-dipoles.
Many classical reactions involving carbon–carbon or carbon–heteroatom bond formation can be catalyzed by Lewis acids. Examples include the Friedel-Crafts reaction, the aldol reaction, and various pericyclic processes that proceed slowly at room temperature, such as the Diels-Alder reaction and the ene reaction. In addition to accelerating the reactions, Lewis acid catalysts are able to impose regioselectivity and stereoselectivity in many cases.
Early developments in Lewis acid reagents focused on easily available compounds such as TiCl4, BF3, SnCl4, and AlCl3. Over the years, versatile catalysts bearing ligands designed for specific applications have facilitated improvement in both reactivity and selectivity of Lewis acid-catalyzed reactions. More recently, Lewis acid catalysts with chiral ligands have become an important class of tools for asymmetric catalysis.
Challenges in the development of Lewis acid catalysis include inefficient catalyst turnover (caused by catalyst affinity for the product) and the frequent requirement of two-point binding for stereoselectivity, which often necessitates the use of auxiliary groups.
In reactions with polar mechanisms, Lewis acid catalysis often involves binding of the catalyst to Lewis basic heteroatoms and withdrawing electron density, which in turn facilitates heterolytic bond cleavage (in the case of Friedel-Crafts reaction) or directly activates the substrate toward nucleophilic attack (in the case of carbonyl addition reactions). The dichotomy can have important consequences in some reactions, as in the case of Lewis acid-promoted acetal substitution reactions, where the SN1 and SN2 mechanisms shown below may give different stereochemical outcomes. Studying the product ratio in a bicyclic system, Denmark and colleagues showed that both mechanisms could be operative depending on the denticity of the Lewis acid and the identity of the R' group.
In Diels-Alder and 1,3-dipolar cycloaddition reactions, Lewis acids lower the LUMO energy of the dienophile or dipolarophile, respectively, making it more reactive toward the diene or the dipole.
Among the types of reactions that can be catalyzed by Lewis acids, those with carbonyl-containing substrates have received the greatest amount of attention. The first major discovery in this area was in 1960, when Yates and Eaton reported the significant acceleration of the Diels-Alder reaction by AlCl3 when maleic anhydride is the dienophile.
Early theoretical studies that depended on frontier orbital analysis established that Lewis acid catalysis operates via lowering of the dienophile's LUMO energy. Recent studies, however, have shown that this rationale behind Lewis acid-catalyzed Diels-Alder reactions is incorrect. It is found that Lewis acids accelerate the Diels-Alder reaction by reducing the destabilizing steric Pauli repulsion between the interacting diene and dienophile and not by lowering the energy of the dienophile's LUMO and consequently, enhancing the normal electron demand orbital interaction. The Lewis acid bind via a donor-acceptor interaction to the dienophile and via that mechanism polarizes occupied orbital density away from the reactive C=C double bond of the dienophile towards the Lewis acid. This reduced occupied orbital density on C=C double bond of the dienophile will, in turn, engage in a less repulsive closed-shell-closed-shell orbital interaction with the incoming diene, reducing the destabilizing steric Pauli repulsion and hence lowers the Diels-Alder reaction barrier. In addition, the Lewis acid catalyst also increases the asynchronicity of the Diels-Alder reaction, making the occupied π-orbital located on the C=C double bond of the dienophile asymmetric. As a result, this enhanced asynchronicity leads to an extra reduction of the destabilizing steric Pauli repulsion as well as a diminishing pressure on the reactants to deform, in other words, it reduced the destabilizing activation strain (also known as distortion energy). This working catalytic mechanism is known as Pauli-lowering catalysis, which is operative in a variety of organic reactions.