Frustrated Radical Pairs: Insights from EPR Spectroscopy

Progress in frustrated Lewis pair (FLP) chemistry has revealed the importance of the main group elements in catalysis, opening new avenues in synthetic chemistry. Recently, new reactivities of frustrated Lewis pairs have been uncovered that disclose that certain combinations of Lewis acids and bases undergo single‐electron transfer (SET) processes. Here an electron can be transferred from the Lewis basic donor to a Lewis acidic acceptor to generate a reactive frustrated radical pair (FRP). This minireview aims to showcase the recent advancements in this emerging field covering the synthesis and reactivities of frustrated radical pairs, with extensive highlights of the results from Electron Paramagnetic Resonance (EPR) spectroscopy to explain the nature and stability of the different radical species observed.     

Interaction of Metal Oxido Compounds with B(C6F5)3

Lewis acid–base pair chemistry has been placed on a new level with the discovery that adduct formation between an electron donor (Lewis base) and acceptor (Lewis acid) can be inhibited by the introduction of steric demand, thus preserving the reactivity of both Lewis centers, resulting in highly unusual chemistry. Some of these highly versatile frustrated Lewis pairs (FLP) are capable of splitting a variety of small molecules, such as dihydrogen, in a heterolytic and even catalytic manner. This is in sharp contrast to classical reactions where the inert substrate must be activated by a metal-based catalyst. Very recently, research has emerged combining the two concepts, namely the formation of FLPs in which a metal compound represents the Lewis base, allowing for novel chemistry by using the heterolytic splitting power of both together with the redox reactivity of the metal. Such reactivity is not restricted to the metal center itself being a Lewis acid or base, also ancillary ligands can be used as part of the Lewis pair, still with the benefit of the redox-active metal center nearby. This Minireview is designed to highlight the novel reactions arising from the combination of metal oxido transition-metal or rare-earth-metal compounds with the Lewis acid B(C₆F₅)₃. It covers a wide area of chemistry including small molecule activation, hydrogenation and hydrosilylation catalysis, and olefin metathesis, substantiating the broad influence of the novel concept. Future goals of this young and exciting area are briefly discussed.     

Frustrated Lewis Pairs Comprising Nitrogen Lewis Acids for Si–H Bond Activation

N-heterocyclic nitrogen Lewis acids are a recent addition to the field of organic chemistry. Based on nitrenium cations, these acids where previously shown to generate Lewis adducts when combined with the appropriate Lewis bases. Herein, a triazinium-based Lewis acid was combined with tBu₃P to generate a frustrated Lewis pair (FLP) capable of cleaving, for the first time, Si−H bonds in silanes. Whereas low yields were initially encountered owing to insufficient Lewis acidity, a new nitrenium-based Lewis acid was synthesized, and its superior Lewis acidity was experimentally and computationally confirmed. A FLP based on this acid cleaved the Si−H bond in PhSiH₃, generating the triazane product in a quantitative yield. This unprecedented N−H triazane was fully characterized by multinuclear NMR techniques and single-crystal X-ray crystallography. A new class of compounds, N-H triazanes display the potential capacity to participate in hydride transfer reactions.     

Rational Development of a Metal-Free Bifunctional System for the C−H Activation of Methane: A Density Functional Theory Investigation

The activation or heterolytic splitting of methane, a challenging substrate usually restricted to transition metals, has so far proven elusive in experimental frustrated Lewis pair (FLP) chemistry. In this article, we demonstrate, using density functional theory (DFT), that 1-aza-9-boratriptycene is a conceptually simple intramolecular FLP for the activation of methane. Systematic comparison with other FLP systems allows to gain insight into their reactivity with methane. The thermodynamics and kinetics of methane activation are interpreted by referring to the analysis of the natural charges and by employing the distortion-interaction/activation strain (DIAS) model. These showed that the nature of the Lewis base influences the selectivity over the reaction pathway, with N Lewis bases favoring the deprotonation mechanism and P bases the hydride abstraction one. The lower barrier of activation for 1-aza-9-boratriptycene and the higher products stability are due to a better interaction energy than its counterparts, itself due to electrostatic interactions with the methane moiety, favorable orbital overlaps allowed by the side-attack, and space proximity between the B and N atoms.     

CO2‐Cross‐Linked Frustrated Lewis Networks as Gas‐Regulated Dynamic Covalent Materials

The design of structurally dynamic molecular networks can offer strategies for fabricating stimuli‐responsive adaptive materials. Herein we first report a gas‐responsive dynamic gel system based on frustrated Lewis pair (FLP) chemistry. Two trefoil‐like molecules with bulky triphenylborane and triphenylphosphine groups are synthesized as complementary Lewis acid and base with trivalent sites. They can together bind CO₂ gas molecules and further form a cross‐linked network via the bonding interactions between FLPs and CO₂. Such CO₂‐bridged dative linkages are shown to be dynamic covalent bonds, which endow the frustrated Lewis network with adaptable behaviors and unprecedented gas‐regulated viscoelastic, mechanical, and self‐healing performance. This study is an initial attempt to apply the FLP concept in materials chemistry, but we believe that this strategy will open a promising future for gas‐sensitive smart materials.     

Metal-free catalytic hydrogenation of polar substrates by frustrated Lewis pairs

In 2006, our group reported the first metal-free systems that reversibly activate hydrogen. This finding was extended to the discovery of "frustrated Lewis pair" (FLP) catalysts for hydrogenation. It is this catalysis that is the focal point of this article. The development and applications of such FLP hydrogenation catalysts are reviewed, and some previously unpublished data are reported. The scope of the substrates is expanded. Optimal conditions and functional group tolerance are considered and applied to targets of potential commercial significance. Recent developments in asymmetric FLP hydrogenations are also reviewed. The future of FLP hydrogenation catalysts is considered.     

Interaction between Spirosilanes and Lewis Bases: from Coordination to Frustration

In this work, the interaction between Lewis bases, especially N-heterocyclic carbenes (NHCs), and hindered neutral silicon derivatives featuring high Lewis acidity is described. The formation of normal and abnormal Lewis adducts could be controlled by varying the acidity of the corresponding tetravalent spiro organosilane. Some DFT calculations permitted to gain insight into the thermodynamics of the NHC–spirosilane interaction featuring various NHCs differing in size and σ-donor capacity. Spirosilanes are introduced as new Lewis partners in frustrated Lewis pair (FLP) chemistry and some FLP-type reactivities are presented, in particular the activation of formaldehyde that could occur with both hindered NHCs and phosphines.     

Versatile Catalytic Hydrogenation Using A Simple Tin(IV) Lewis Acid

Despite the rapid development of frustrated Lewis pair (FLP) chemistry over the last ten years, its application in catalytic hydrogenations remains dependent on a narrow family of structurally similar early main‐group Lewis acids (LAs), inevitably placing limitations on reactivity, sensitivity and substrate scope. Herein we describe the FLP‐mediated H₂ activation and catalytic hydrogenation activity of the alternative LA iPr₃SnOTf, which acts as a surrogate for the trialkylstannylium ion iPr₃Sn⁺, and is rapidly and easily prepared from simple, inexpensive starting materials. This highly thermally robust LA is found to be competent in the hydrogenation of a number of different unsaturated functional groups (which is unique to date for main‐group FLP LAs not based on boron), and also displays a remarkable tolerance to moisture.     

Synthesis and reactivity of electron poor allenes: formation of completely organic frustrated Lewis pairs

The synthesis of several electron poor allenes bearing electron withdrawing substituents is described and their use as Lewis acids in the field of frustrated Lewis pair (FLP) chemistry reported. At room temperature the combination of N-heterocyclic carbenes (NHC) with the allenes under study invariably afforded the corresponding Lewis adducts; however, at -78 °C this reaction is in most of the cases inhibited and kinetically induced organic FLPs are formed. Under these conditions the activation of S-S bonds in disulfides has been achieved in excellent yields.     

Frustrated Lewis Pair Mediated 1,2-Hydrocarbation of Alkynes

Frustrated Lewis pair (FLP) chemistry enables a rare example of alkyne 1,2-hydrocarbation with N-methylacridinium salts as the carbon Lewis acid. This 1,2-hydrocarbation process does not proceed through a concerted mechanism as in alkyne syn-hydroboration, or through an intramolecular 1,3-hydride migration as operates in the only other reported alkyne 1,2-hydrocarbation reaction. Instead, in this study, alkyne 1,2-hydrocarbation proceeds by a novel mechanism involving alkyne dehydrocarbation with a carbon Lewis acid based FLP to form the new C−C bond. Subsequently, intermolecular hydride transfer occurs, with the Lewis acid component of the FLP acting as a hydride shuttle that enables alkyne 1,2-hydrocarbation.     

Metal‐Free Hydrogenation of Unsaturated Hydrocarbons Employing Molecular Hydrogen

The metal‐free activation of hydrogen by frustrated Lewis pairs (FLPs) is a valuable method for the hydrogenation of polarized unsaturated molecules ranging from imines, enamines, and silyl enol ethers to heterocycles. However, one of the most important applications of hydrogenation technology is the conversion of unsaturated hydrocarbons into alkanes or alkenes. Despite the fast development of the FLP chemistry, such reactions proved as highly challenging. This Minireview provides an overview of the basic concepts of FLP chemistry, the challenge in the hydrogenation of unsaturated hydrocarbons, and first solutions to this central transformation.     

"Frustrated Lewis pair" hydrogenations

This perspective article discusses developments of metal-free hydrogenation catalysts derived from "frustrated Lewis pair" (FLP) systems. The range of catalysts uncovered and the applications to reductions of imines, aziridines, enamines, silyl enol ethers, diimines, metallocene derivatives and nitrogen-based heterocycles are described. In addition, FLP aromatic reduction of aniline derivatives to the cyclohexylamine analogs is discussed. The potential applications of these metal-free reductions are considered.     

Frustrated Lewis pairs beyond the main group: synthesis, reactivity, and small molecule activation with cationic zirconocene-phosphinoaryloxide complexes

The extension of the frustrated Lewis pair (FLP) concept to the transition series with cationic zirconocene-phosphinoaryloxide complexes is demonstrated. Such complexes mimic the reactivity of main group FLPs in reactions such as heterolytic hydrogen cleavage, CO(2) activation, olefin and alkyne addition, and ring-opening of tetrahydrofuran. The interplay between sterics and electronics is shown to have an important role in determining the reactivity of these compounds with hydrogen in particular. The Zr-H species generated from the heterolytic activation of hydrogen is shown to undergo insertion reactions with both CO(2) and CO. Crucially, these transition metal FLPs are markedly more reactive than main group systems in many cases, and in addition to the usual array of reactions they demonstrate unprecedented reactivity in the activation of small molecules. This includes S(N)2 and E2 reactions with alkyl chlorides and fluorides, enolate formation from acetone, and the cleavage of C-O bonds to facilitate S(N)2 type reactions with noncyclic dialkyl ethers.     

A P−H Functionalized Al/P Frustrated Lewis Pair: Substrate Activation and Selective Hydrogen Transfer

Hydroalumination of an alkynylphosphine gave an unprecedented P?H functionalized frustrated Lewis pair (FLP). The reactive P?H group does not influence the typical FLP properties, but the activation of substrates follows a new reaction pattern involving hydrogen transfer to yield unusual compounds with phosphaurea, iminophosphine, or phosphanyltriazene structural motifs.     

Frustrated Lewis Pair Mediated 1,2‐Hydrocarbation of Alkynes

Frustrated Lewis pair (FLP) chemistry enables a rare example of alkyne 1,2‐hydrocarbation with N‐methylacridinium salts as the carbon Lewis acid. This 1,2‐hydrocarbation process does not proceed through a concerted mechanism as in alkyne syn‐hydroboration, or through an intramolecular 1,3‐hydride migration as operates in the only other reported alkyne 1,2‐hydrocarbation reaction. Instead, in this study, alkyne 1,2‐hydrocarbation proceeds by a novel mechanism involving alkyne dehydrocarbation with a carbon Lewis acid based FLP to form the new C−C bond. Subsequently, intermolecular hydride transfer occurs, with the Lewis acid component of the FLP acting as a hydride shuttle that enables alkyne 1,2‐hydrocarbation.     

Frustrated Lewis Pair Chemistry: Searching for New Reactions

Frustrated Lewis pair chemistry has taken a steep development in the recent years. It offers possibilities of developing new variants of known reactions and of finding new chemical transformations. This is demonstrated and described by the recently developed FLP‐formylborane chemistry, which has led to the formation of the unique (η²‐formylborane)FLP adducts and opened a way of preparing a genuine formylborane compound, which shows an interesting follow‐up chemistry. FLPs have helped finding phosphorus analogues of the enamine Stork reaction and the Claisen reaction. These reactions lead to new organophosphorus compounds and they make new phosphane/borane systems available. P/B FLPs add to a variety of small main group element oxides. They undergo 1,2‐addition reactions to CO₂, SO₂ and other heterocumulenes and they feature unique 1,1‐addition reactions to carbon monoxide, to isonitriles and even to nitric oxide (NO), the latter yielding examples of a new class of persistent nitroxide radicals, the FLPNO nitroxyls. Eventually, some remarkable radical reactions of FLPs and related compounds are briefly mentioned.     

Probing the Charge Transfer in a Frustrated Lewis Pair by Resonance Raman Spectroscopy and DFT Calculations

A classical Lewis adduct derives from a covalent bond between a Lewis acid and a base. When the adduct formation is precluded by means of steric hindrance the association of the respective acid-base molecular system is defined as a frustrated Lewis pair (FLP). In this work, the archetypal FLP Mes₃P/B(C₆F₅)₃ was characterized for the first time by resonance Raman spectroscopy, and the results were supported by density functional theory (DFT) calculations. The charge transfer nature of the lowest energy electronic transition, from phosphine to borane, was confirmed by the selective enhancement of the Raman bands associated to the FLP chromophore at resonance condition. Herein, we demonstrate the use of resonance Raman spectroscopy as a distinguished technique to probe the weak interaction involved in FLP chemistry.     

Facile Modulation of FLP Properties: A Phosphinylvinyl Grignard Reagent and Ga/P‐ and In/P2‐Based Frustrated Lewis Pairs

An Al/P‐based frustrated Lewis pair (FLP) reacted with PhMgCl by an unexpected transmetalation and formation of a phosphinylvinyl Grignard reagent. This compound is well suited for the transfer of the basic FLP component to other Lewis acidic metal atoms and allowed the generation of a Ga/P and an In/P₂ FLP. The Ga FLP showed a behavior different to that of the corresponding Al FLP, the In FLP allowed the chelating coordination of an Au atom by Au−Cl bond activation.     

A Combined “Electrochemical–Frustrated Lewis Pair” Approach to Hydrogen Activation: Surface Catalytic Effects at Platinum Electrodes

Herein, we extend our “combined electrochemical–frustrated Lewis pair” approach to include Pt electrode surfaces for the first time. We found that the voltammetric response of an electrochemical–frustrated Lewis pair (FLP) system involving the B(C₆F₅)₃/[HB(C₆F₅)₃]^? redox couple exhibits a strong surface electrocatalytic effect at Pt electrodes. Using a combination of kinetic competition studies in the presence of a H atom scavenger, 6‐bromohexene, and by changing the steric bulk of the Lewis acid borane catalyst from B(C₆F₅)₃ to B(C₆Cl₅)₃, the mechanism of electrochemical–FLP reactions on Pt surfaces was shown to be dominated by hydrogen‐atom transfer (HAT) between Pt, [Pt?H] adatoms and transient [HB(C₆F₅)₃] ^? electrooxidation intermediates. These findings provide further insight into this new area of combining electrochemical and FLP reactions, and proffers additional avenues for exploration beyond energy generation, such as in electrosynthesis.     

二氧化铈表面构建固体“受阻”Lewis酸碱对用于小分子活化

Solid materials containing frustrated Lewis pairs (FLPs) as active sites have attracted much attention due to their ability to activate and transform small molecules. However, it is still highly challenging to precisely construct FLP sites on the surfaces of nanomaterials, thereby limiting the applications of these materials. Nanostructured ceria (CeO₂) is commonly employed as a catalyst or functional support, and exhibits both Lewis acid and basic properties as well as abundant and easily regulated surface defects, which originate from the reversible Ce³⁺/Ce⁴⁺ redox pair. When the Lewis acid and base sites of CeO₂ are independent of each other, the combined Lewis acid-base sites play a similar role to that of homogeneous FLP sites. Thus, the rich surface properties of nanostructured CeO₂ provide significant potential for the construction of solid FLPs.