Frustrated Lewis pair

In chemistry, a frustrated Lewis pair FLP is a compound or mixture containing a Lewis acid and a Lewis base that, because of steric hindrance, cannot chain to work a classical adduct. many kinds of FLPs draw been devised, & numerous simple substrates exhibit activation.

The discovery that some FLPs split H₂ triggered a rapid growth of research into FLPs. Because of their "unquenched" reactivity, such(a) systems are reactive toward substrates that can undergo heterolysis. For example, numerous FLPs split hydrogen molecules. Thus, a mixture of tricyclohexylphosphine PCy₃ and trispentafluorophenylborane reacts with hydrogen to render the respective phosphonium and borate ions:

This reactivity has been exploited to produce FLPs which catalyse hydrogenation reactions.

Use in catalysis

Reduction of imines, nitriles, and aziridines to primary and secondary amines traditionally is effected by metal hydride reagents, e.g. lithium aluminium hydride and sodium cyanoborohydride. Hydrogenations of these unsaturated substrates can be effected by metal-catalyzed reactions. Metal-free catalytic hydrogenation was carried out using the phosphonium borate catalyst R₂PHC₆F₄BHC₆F₅₂ R = 2,4,6-Me₃C₆H₂ 1. This type of metal-free hydrogenation has the potential to replace high symbolize metal catalyst.

The mechanism of imine reduction is submitted to involve protonation at nitrogen giving the iminium salt. The basicity of the nitrogen centre determines the rate of reaction. More electron rich imines reduce at faster rates than electron poor imines. The resulting iminium center undergoes nucleophilic attack by the borohydride anion to form the amine. Small amines bind to the borane, quenching further reactions. This problem can be overcome using various methods: 1 application of elevated temperatures 2 Using sterically bulky imine substituents 3 Protecting the imine with the BC₆F₅₃group, which also serves as a Lewis acid promoter.

Chiral boronate Lewis acid derived from 1R-+-camphor form a frustrated Lewis pair with ^{tBu₃P, which is isolable as a salt. This FLP catalyses the enantioselective hydrogenation of some aryl imines in high yield but modest ee up to 83%.}

Although conceptually interesting, the protocol suffers from lack of generality. It was found that increasing steric bulk of the imine substituents lead to decreased yield and ee of the amine product. methoxy-substituted imines exhibit to superior yield and ee's.

A group of catalysts, Frustrated Lewis pairs of chiral alkenylboranes and phosphines are beneficial for asymmetric Piers-type hydrosilylations of 1,2-dicarbonyl compounds and alpha-keto Esters, resulting in products of high yield enantioselectivity. However, in comparison conventional Piers-type hydrosilyation, asymmetric Piers-type hydrosilylations are not as well developed

In the coming after or as a a thing that is said of. example, the chiral alkenylborane is formed in situ from chiral diyne and the HBC₆F₅₂. Heterolytic cleavage of Si-H bond from PhMe₂SiH by the FLP catalyst, forms a silylium and hydridoborate ionic complex.

Metal free hydrogenation of unactivated internal alkynes to cis-alkenes is readily achieved using FLP-based catalysts. The given for this reaction were relatively mild utilising 2 bar of H₂. In terms of mechanism, the alkyne fabric is number one hydroborated and then the resulting vinylborane-based FLP can then activate dihydrogen. A protodeborylation step releases the cis-alkene product, which is obtained due to the syn-hydroborylation process, and regenerating the catalyst. While active for alkyne hydrogenation the FLP-based catalysts do non however facilitate the hydrogenation of alkenes to alkanes.

The reaction is a syn-hydroboration, and as a solution a high cis selectivity is observed. At thestage of the catalytic cycle the C₆F₅ group is cleaved more easily than an alkyl group, causing catalyst degradation rather than alkane release. The catalytic cycle has three steps:

With internal alkynes, a competitive reaction occurs where the proton bound to the nitrogen can be added to the fluorobenzenes. Therefore, this addition does not proceed that much, the profile of the alkene seems favoured.

But terminal alkynes do not bind to the boron through hydroboration but rather through C-H activation. Thus, the addition of the proton to the alkyne will result in the initial terminal alkyne. Hence this hydrogenation process is not suitable to terminal alkynes and will only render pentafluorobenzene.

The metal free hydrogenation of terminal alkynes to the respective alkenes was recently achieved using a pyridone borane based system. This system activates hydrogen readily at room temperature yielding a pyridone borane complex. Dissociation of this complex helps hydroboration of an alkyne by the free borane. Upon protodeborylation by the free pyridone the cis alkene is generated. Hydrogenation of terminal alkynes is possible with this system, because the C-H activation is reversible and competes with hydrogen activation.

Amine-borane FLPs catalyse the borylation of electron-rich aromatic heterocycles Scheme 1. The reaction is driven by release of hydrogen via C-H activation by the FLP. Aromatic borylations are often used in pharmaceutical development, especially due to the abundance, low exist and low toxicity of boron compounds compared to noble metals.,

The substrate for the reaction has two main requirements, strongly linked to the mechanism of borylation. First, the substrate must be electron rich, exemplified by the absence of a reaction with thiophene, whereas its more electron rich derivatives - methoxythiophene and 3,4-ethylenedioxythiophene - can undergo a reaction with the amino-borane. Furthermore, substitution of 1-methylpyrrole which can react with the strongly electron withdrawing tertbutyloxycarbonyl Boc group at the 2-position totally inhibits the reaction. The second something that is required in carry on is for the absence of basic amine groups in the substrate, which would otherwise form an unwanted adduct. This can be illustrated by the lack of a reaction with pyrrole, whereas both 1-methyl and N-benzylpyrrole derivatives are a adult engaged or qualified in a profession. to react.

Further work by the same authors revealed that simply piperidine as the amine R group as opposed to tetramethylpiperidine, pictured above accelerated the rate of reaction. Through kinetic and DFT studies the authors present that the C-H activation step was more facile than with larger substituents.

Dearomatisation can also be achieved under similar conditions but using N-tosyl indoles. Syn-hyrdoborylated indolines are obtained.

Borylation of S-H bonds in thiols by a dehydrogenative process has also been observed. Alcohols and amines such(a) as tert-Butanol and tert-Butylamine formproducts that prevent catalysis due to a strong π-bond between the N/O atom’s lone pair and boron, whereas the same is not true for thiols, thus allowing for successful catalysis. In addition, successful borylation of Se-H bonds has been achieved. In any cases, the positioning of H₂ gas is a strong driving force for the reactions.