Fact-checked by Grok 2 weeks ago

Frustrated Lewis pair

A frustrated Lewis pair (FLP) is a chemical system comprising a sterically encumbered acid and a base that are prevented from forming a classical donor-acceptor , thereby preserving their independent reactivity to cooperatively activate inert small molecules such as dihydrogen (H₂) or (CO₂). This concept, first demonstrated in 2006 by Douglas W. Stephan and colleagues through the reversible heterolytic cleavage of H₂ using a phosphine-borane pair, challenged the prevailing view that such activations required catalysts. The term "frustrated Lewis pair" was coined by Stephan in 2007 to describe these sterically hindered systems, building on earlier observations of in acid-base interactions dating back to 1942. FLPs have revolutionized chemistry by enabling metal-free for a wide array of transformations, including the of imines, alkenes, alkynes, and carbonyl compounds, as well as and reactions. Their ability to engage in both two-electron processes and, more recently identified, single-electron transfer (SET) mechanisms—forming radical ion pairs—has expanded their utility to and radical-based synthetic methodologies. For instance, classic intermolecular FLPs like P(t-Bu)₃/B(C₆F₅)₃ activate H₂ via SET, as confirmed by () spectroscopy, highlighting their versatility beyond traditional pathways. Beyond homogeneous systems, FLPs have been integrated into heterogeneous and supramolecular frameworks, such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), to enhance stability and recyclability for applications in CO₂ capture, reduction to or , and selective C-F bond activation in fluorocarbons. These advances, documented in reviews up to 2025, underscore FLPs' growing role in sustainable , , and , with ongoing research exploring intramolecular variants, high-density supported systems, chiral catalysts, and advanced heterogeneous designs for improved efficiency.

Definition and History

Core Concept

In classical Lewis acid-base chemistry, a Lewis acid acts as an electron-pair acceptor while a Lewis base serves as an electron-pair donor, typically forming a stable dative bond or , as exemplified by the interaction between (BH₃) and (NH₃) to yield H₃B·NH₃. This formation neutralizes the reactive sites, rendering the pair inert toward further interactions. In contrast, frustrated Lewis pairs (FLPs) consist of sterically encumbered Lewis acids and bases that are prevented from forming such classical due to bulky substituents, which impose spatial constraints and maintain the independent reactivity of each component. This "frustration" arises primarily from steric hindrance, though electronic factors can also play a role, allowing the acid and base to engage in cooperative, bifunctional reactivity with external substrates. FLPs are generally constructed from main-group elements, most commonly group 13 Lewis acids such as perfluorophenylboranes and group 15 Lewis bases like phosphines or amines bearing large substituents. A prototypical example is the intermolecular pair formed by trimesitylphosphine (Mes₃P, where Mes = 2,4,6-trimethylphenyl) and tris(pentafluorophenyl)borane (B(C₆F₅)₃), where the bulky mesityl groups on phosphorus and the fluorinated aryls on boron preclude close approach and dative bond formation. Intramolecular variants, such as those linked by a rigid backbone (e.g., phosphine-borane systems connected via a phenylene bridge), similarly rely on geometric constraints to sustain frustration. These designs ensure that the Lewis acid's empty orbital and the Lewis base's lone pair remain accessible for substrate activation. The foundational concepts of Lewis acidity and basicity, originally defined by in 1923 as electron-pair acceptance and donation, respectively, are central to FLPs but are adapted through the selection of sterically demanding and electronically tuned components to avoid quenching. Strong Lewis acids in FLPs, like B(C₆F₅)₃, feature electron-deficient centers enhanced by electronegative substituents, while bases such as Mes₃P or tBu₃P possess high nucleophilicity shielded by voluminous alkyl or aryl groups. The term "frustrated Lewis pair" was coined by Douglas W. Stephan in 2007 to describe these non-quenching combinations, marking a in main-group chemistry. This frustration enables unprecedented reactivity, such as the heterolytic cleavage of dihydrogen (H₂) into hydridic and protic fragments, demonstrating the pairs' potential for small-molecule activation.

Discovery and Key Milestones

The discovery of frustrated Lewis pairs (FLPs) began in 2006 when Douglas W. Stephan's research group at the observed that the sterically encumbered intramolecular phosphine-borane Mes₂P-(p-C₆F₄)-B(C₆F₅)₂ reversibly activated dihydrogen (H₂) at under , forming the zwitterionic product [Mes₂PH-(p-C₆F₄)-BH(C₆F₅)₃]⁻. This breakthrough occurred serendipitously during efforts to synthesize Lewis acid-base adducts, which failed due to steric hindrance, allowing the pair to cooperatively cleave H₂ instead. The finding challenged the prevailing view that H₂ activation required transition metals and opened new avenues in main-group chemistry. Shortly thereafter, intermolecular variants, such as Mes₃P/B(C₆F₅)₃, were shown to achieve similar reactivity. In , the scope expanded rapidly with demonstrations of catalytic using FLPs, including the of imines, nitriles, and silylenol ethers by variants of the original P/B system, achieving high yields under mild conditions. Concurrently, explorations revealed that other , such as B(C₆F₄H)₃ and perfluorinated diarylboranes, could replace B(C₆F₅)₃ while maintaining reactivity toward H₂, broadening the design principles for FLPs. The term "frustrated Lewis pair" was formally coined in these works to describe the unquenched reactivity arising from steric . Between and , FLP evolved from serendipitous observations to rationally designed systems, with demonstrations extending beyond phosphorus-boron pairs to other main-group elements. Notable advances included nitrogen-boron FLPs, such as those using bulky anilines or pyridines with B(C₆F₅)₃, which activated H₂ and small molecules like CO₂. Collaboration between Stephan and Gerhard Erker introduced carbon-boron intramolecular FLPs in , enabling reversible CO₂ binding and further H₂ splitting. By 2009, the first purely intermolecular FLPs beyond the initial P/B were reported, using amine-borane combinations for small-molecule activation, marking a shift toward tunable, non-covalent systems. These milestones transformed FLPs into a versatile platform, earning widespread recognition in main-group . Post-2010, FLP chemistry continued to advance, incorporating single-electron transfer mechanisms for radical-based reactions and integration into heterogeneous supports like metal-organic frameworks for enhanced applications in CO₂ reduction and C-F bond activation, as reviewed up to 2023.

Fundamental Principles

Lewis Acid-Base Interactions

In Lewis acid-base theory, a Lewis acid functions as an electron-pair acceptor, while a Lewis base acts as an electron-pair donor. In the context of frustrated Lewis pairs (FLPs), prototypical Lewis acids include sterically encumbered boranes such as tris(pentafluorophenyl)borane, B(C₆F₅)₃, which exhibits strong electron-accepting ability due to the electron-withdrawing perfluorophenyl substituents. Complementary Lewis bases, such as tri-tert-butylphosphine, tBu₃P, serve as electron donors with high basicity, yet their combination avoids classical adduct formation owing to mutual steric repulsion. Steric frustration in FLPs is quantified using parameters like the percent buried volume (%Vbur), which measures the spatial occupancy of substituents around the Lewis acid or base site within a defined spherical region (typically r = 3.5 , calculated via tools like SambVca). For instance, B(C₆F₅)₃ displays a %Vbur of 58.9% (at r = 3.50 ) in its adduct, reflecting moderate steric demand that, when paired with bulky bases like tBu₃P (with %Vbur ≈ 44%), prevents dative bond formation and preserves reactive sites. Examples of sterically demanding groups include the tert-butyl moieties on , which create a cone-like , and the pentafluorophenyl rings on , enhancing both steric bulk and electronic withdrawal. Electronic factors in FLPs allow fine-tuning of acidity and basicity without inducing coordination, enabling tailored reactivity profiles. Computational metrics such as the global electrophilicity index (GEI) provide a -independent measure of Lewis acidity; for B(C₆F₅)₃, the GEI value is approximately 3.7 eV (e.g., 3.65 eV at B3LYP/def2-TZVP), surpassing less acidic like BPh₃. Substituent modifications, such as introducing more electron-withdrawing groups on the acid or alkyl donors on the , adjust these properties while maintaining . This non-coordinating nature of FLPs parallels classical frustrated systems in coordination chemistry, where steric hindrance between metal centers and ligands promotes cooperative substrate activation rather than stable formation. In FLPs, the preserved availability of individual sites facilitates unique reactivity, such as the heterolytic splitting of dihydrogen.

Steric Frustration Mechanism

The steric frustration mechanism in frustrated pairs (FLPs) relies on the incorporation of bulky substituents on both the Lewis acid and Lewis base, which impose geometric constraints that inhibit the formation of a stable dative . This "frustration" maintains the Lewis acidity and basicity of the respective sites, enabling cooperative interactions with substrates rather than mutual . In phosphorus-borane FLPs, the absence of strong B-P bonding is quantified by crystallographic analyses of intramolecular variants, where B-P distances typically exceed 3.4 —the approximate sum of the van der Waals radii for (1.92 ) and (1.80 )—often reaching 4.0–5.0 or more, in contrast to the ~2.0 bond lengths observed in classical phosphine-borane adducts. A key thermodynamic aspect of this mechanism is the enhanced entropy in FLP systems compared to classical Lewis acid-base adducts. The lack of a rigid dative bond affords the acid and base components greater translational and rotational freedom, increasing the overall entropy and favoring the dissociated state in solution. Computational studies corroborate this, showing that the entropic penalty for adduct formation is significant due to the loss of independent motion in the frustrated pair. FLPs can be classified as intermolecular or intramolecular based on the connectivity of the acid and base sites. Intermolecular FLPs consist of separate, sterically encumbered molecules, such as the combination of tris(2,4,6-trimethylphenyl)phosphine (Mes3P) and tris(pentafluorophenyl)borane (B(C6F5)3), where the bulky mesityl groups on phosphorus and pentafluorophenyl ligands on boron prevent close approach and adduct formation. Intramolecular FLPs, in contrast, feature the acid and base tethered by a covalent linker, enforcing a fixed separation; a representative example is o-(di-tert-butylphosphino)phenyl-bis(pentafluorophenyl)borane, where the rigid o-phenylene bridge maintains a B-P separation of approximately 4.1 Å in the open conformation, as determined by X-ray diffraction. These linked systems often exhibit tunable frustration by varying linker length or flexibility, such as in ethylene-bridged variants like (tBu2P-CH2-CH2-B(C6F5)2). Experimental evidence for the persistence of independent and sites in FLPs is provided by . 31P and 11B NMR reveals distinct chemical shifts for the (typically δ 0 to 60 , e.g., ≈56 for free tBu₃P) and (δ ≈ -15 for B(C₆F₅)₃) centers, with patterns consistent with uncoordinated , unlike the broadened or shifted signals in adducts. Similarly, confirms the integrity of the sites through unchanged vibrational modes, such as the B-C stretch at ~1300 cm-1 for the free and P-C stretches around 1000 cm-1 for the , without evidence of new P-B vibrational bands expected in bonded pairs. These observations underscore the unquenched reactivity inherent to the frustrated state.

Small Molecule Activation

Dihydrogen Activation

The groundbreaking activation of dihydrogen by frustrated Lewis pairs (FLPs) demonstrated the potential for metal-free catalysis of small molecule reactions, relying on steric frustration to prevent classical Lewis acid-base adduct formation and enable cooperative heterolytic cleavage of the H-H bond. The first reported example involved the intermolecular FLP composed of dimesitylphosphine (Mes₂PH) and tris(pentafluorophenyl)borane (B(C₆F₅)₃), which reacts with H₂ under mild conditions to yield the zwitterionic phosphonium hydridoborate salt. This reaction proceeds at room temperature in toluene solvent, highlighting the accessibility of the process without the need for harsh conditions typically required in metal-based systems. The transformation can be represented by the following equation: \text{Mes}_2\text{PH} + \text{B(C}_6\text{F}_5)_3 + \text{H}_2 \rightarrow [\text{Mes}_2\text{PH}_2]^+ [\text{HB(C}_6\text{F}_5)_3]^- The product features a protonated phosphine cation and a hydrido borate anion, confirming the heterolytic splitting of H₂ into H⁺ and H⁻ equivalents. Spectroscopic characterization via ¹H NMR reveals diagnostic signals for the H₂-derived protons, typically appearing as a broad singlet near δ 4.9 ppm for the P-H₂ moiety and a broad quartet near δ -0.8 ppm (³J_{B-H} ≈ 80 Hz) for the B-H unit, consistent with the ionic nature of the zwitterion. These shifts distinguish the activated species from free H₂ (δ 4.6 ppm) and underscore the polarization induced by the FLP components. The scope of dihydrogen activation extends to intramolecular FLPs, where the Lewis acid and base are tethered to facilitate proximity and enhance reactivity. A representative example is the ortho-substituted compound o-(tBu₂P)C₆F₄B(C₆F₅)₂, which undergoes reversible addition of H₂ at ambient conditions, releasing the gas upon mild heating (e.g., 60°C). This reversibility, observed through equilibrium NMR studies, arises from the balanced steric and electronic properties of the system, allowing the zwitterionic to dissociate without permanent bond formation. Such intramolecular designs mitigate entropy losses associated with intermolecular pairs and have paved the way for catalytic cycles. Despite these advances, practical implementation of FLP-mediated H₂ activation faces limitations, including the necessity for non-coordinating solvents such as or hydrocarbons to avoid competitive Lewis base solvation of the boron center. Additionally, the activated and precursors exhibit high sensitivity to protic impurities like H₂O and reactive gases like O₂, which can protonate the or oxidize the , leading to decomposition and necessitating rigorous inert-atmosphere handling.

Activation of Other Molecules

Frustrated Lewis pairs (FLPs) exhibit diverse reactivity with small molecules beyond dihydrogen, enabling heterolytic cleavage and formation of zwitterionic or radical species. A prominent example is the activation of carbon dioxide (CO2), where the combination of tri-tert-butylphosphine (tBu3P) and tris(pentafluorophenyl)borane (B(C6F5)3) forms a stable zwitterionic adduct at room temperature under 1 bar pressure. The reaction involves the phosphorus center binding to the carbon atom and the boron center to an oxygen atom of CO2, resulting in a bent CO2 geometry indicative of activation. This adduct is reversible, with CO2 release upon heating to 80°C under vacuum. In pathways, FLPs can facilitate the conversion of CO2 to derivatives. For instance, the protonated form [tBu3PH]+ [HB(C6F5)3]- , generated from activation by the tBu3P/B(C6F5)3 pair, reacts with CO2 to form the zwitterionic [tBu3PH]+ [O2CB(C6F5)3]-. Subsequent using sources such as borane (Me2NHBH3) or the borane-amine pair [C5H6Me4NH2]/[HB(C6F5)2(C7H11)] , followed by quenching with D2O, yields deuterated (MeOD). This stoichiometric process highlights the potential of FLPs for CO2 utilization, with the O-C bond in the adduct elongated to 1.30 and the B-O bond at 1.55 , reflecting weakened CO2 bonds. FLPs also activate oxygen (O2) through oxidative addition, leading to peroxo or hydroperoxo species. The tBu3P/B(C6F5)3 pair reacts with O2 to form the ionic species [tBu3PH]+ [O2B(C6F5)3]-, where the boron binds the peroxo group, demonstrating reversible O2 addition under ambient conditions. Similar reactivity is observed with nitric oxide (NO), where intramolecular P/B FLPs, such as Mes2P-CH2CH2-B(C6F5)2, add NO across the P-B pair to yield persistent aminoxyl radicals or nitroso-borane adducts, with N-N addition facilitating N-O bond weakening. For unsaturated hydrocarbons, FLPs initiate and hydrosilylation of alkynes and alkenes by polarizing the multiple bonds. For example, the Mes2P-C6H4-B(C6F5)2 intramolecular FLP adds to terminal alkynes, forming borane-phosphonium zwitterions with high (anti-Markovnikov addition). In hydrosilylation, alane/ FLPs, such as iPr3P/Al(C6F5)3, activate silanes like Et3SiH to generate silylium-hydride pairs that add to alkenes, yielding alkylsilanes with E-selectivity for internal alkenes. These activations showcase the versatility of FLP systems, where steric allows selective binding and bond cleavage, varying with the acid/base pair to tune reactivity toward silanes or hydrocarbons.

Theoretical Insights into Activation

Density functional theory (DFT) modeling has provided crucial insights into the mechanism of dihydrogen (H₂) activation by frustrated Lewis pairs (FLPs), revealing a concerted process involving a with low activation barriers typically in the range of 5-10 kcal/mol. These barriers arise from the cooperative interaction between the Lewis and , where the H-H is polarized and cleaved heterolytically, leading to charge-separated products such as [LBH⁺][HB⁻]. The low energy requirements facilitate room-temperature reactivity, distinguishing FLPs from classical Lewis acid-base adducts. At the , orbital interactions play a pivotal role: the empty p-orbital of the acid (e.g., ) accepts electron density from the σ-orbital of H₂, while the filled lone-pair orbital of the (e.g., ) interacts with the σ*-orbital of H₂, effectively polarizing and weakening the H-H . This synergistic model underscores the B-P , where non-additive energy contributions from the acid-base pair enhance the overall activation energetics. Early computational studies from 2007-2010 by Pápai and coworkers on B/P-based FLPs demonstrated this through energy decomposition analyses, showing that charge transfer dominates stabilization at the over electrostatic by an . For FLP design, predictive tools such as topographic steric maps and conceptual DFT reactivity indices enable the optimization of acid-base pairs for H₂ activation. Topographic steric maps quantify the spatial hindrance around , allowing researchers to predict levels and avoid unproductive dative bonding while maintaining proximity for . Reactivity indices, including global electrophilicity and nucleophilicity parameters derived from conceptual DFT, further guide the selection of components by correlating electronic properties with activation barriers and . These tools have been instrumental in rationalizing and forecasting FLP performance in activation.

Catalytic Applications

Hydrogenation Processes

Frustrated Lewis pairs (FLPs) enable metal-free of imines by activating dihydrogen to generate a hydridic (H⁻) and protic (H⁺) , which sequentially add to the C=N bond, delivering the hydride first to form an intermediate, followed by to yield the saturated and regenerate the FLP. The archetypal intermolecular FLP, consisting of P(t-Bu)₃ as the Lewis base and B(C₆F₅)₃ as the Lewis acid, catalyzes the of aryl and alkyl imines under mild conditions of 1–5 bar H₂ at , achieving quantitative yields for substrates like N-benzylideneaniline within hours. This process serves as a H₂ surrogate alternative to traditional metal catalysts, with variants employing HBpin or silanes (e.g., PhSiH₃) for , where the FLP facilitates and hydrosilylation steps to produce in up to 95% yield without gaseous H₂. FLP catalysis extends to nitriles and , leveraging the same H₂ activation to reduce C≡N bonds to primary amines and open aziridine rings to 1,2-diamines, respectively. For nitriles such as , the P(t-Bu)₃/B(C₆F₅)₃ pair operates at 4 bar H₂ and 80°C, delivering in 90–99% yield after 24 hours, with tolerance for electron-withdrawing substituents but slower rates for aliphatic examples. Aziridine reductions, reported concurrently, use similar conditions (5 bar H₂, 60°C) with P(o-tol)₃/B(C₆F₅)₃ to achieve regioselective ring-opening of N-tosylaziridines, yielding vicinal diamines in 85% yield, highlighting FLPs' utility for strained heterocycles. Alkyne semi-hydrogenation by FLPs produces selectively, avoiding over-reduction through the polarized H⁻/H⁺ delivery that favors syn addition and limits coordination. An intramolecular amine-borane FLP, developed in 2013, catalyzes the semi-hydrogenation of to styrene at 10 bar H₂ and 50°C, attaining 88% yield with >95% cis selectivity and minimal byproduct (<5%). Between 2010 and 2015, FLP hydrogenation advanced with the introduction of enantioselective variants, providing metal-free access to chiral amines. The first such system using a chiral bisphosphine/B(C₆F₅)₃ FLP, reported in 2011, hydrogenates cyclic imines at 10 bar H₂ and room temperature, delivering products with up to 83% ee, marking a pivotal step toward asymmetric catalysis. Subsequent refinements, including chiral borane variants, improved ee values to >99% for aryl imines by 2015, expanding the scope while maintaining mild pressures (5–20 bar).

Hydrosilylation and Borylation

Frustrated Lewis pairs (FLPs) facilitate the hydrosilylation of ketones and aldehydes by activating silanes such as PhSiH₃, leading to the formation of silyl ethers with high efficiency under mild conditions. This process often exhibits anti-Markovnikov selectivity in cases involving unsymmetrical silanes or substrates, prioritizing the addition of silicon to the less substituted position. The foundational example involved the strong Lewis acid B(C₆F₅)₃ catalyzing the reaction of PhSiH₃ with various carbonyls, achieving near-quantitative yields for aromatic and aliphatic ketones like , which produced PhCH(OSiH₂Ph)Me. Subsequent advancements employed intermolecular FLPs, such as phosphine-borane combinations, to enhance substrate scope and catalyst stability. In borylation reactions, FLPs enable the direct C-H functionalization of arenes and heteroarenes using (HBpin), providing a metal-free alternative to traditional transition-metal . A landmark 2015 report demonstrated intramolecular FLPs catalyzing the dehydrogenative borylation of electron-rich heteroarenes like furans and thiophenes, yielding borylated products with up to 90% yield and high at the 2-position. These systems, inspired by Hartwig's iridium-catalyzed methods from the early , leverage the FLP's ability to cleave the B-H bond and facilitate C-H insertion without metal involvement, often operating at room temperature. Enantioselective variants of FLP-mediated hydrosilylation have been achieved using chiral or , particularly for substrates, yielding chiral amines with high enantiomeric excess. For instance, a chiral generated via of a with HB(C₆F₅)₂ catalyzed the hydrosilylation of N-aryl with PhSiH₃, affording products with up to 96% and full conversion under mild conditions. Chiral -based FLPs have similarly delivered >90% in reductions, with the steric bulk of the dictating facial selectivity during . The of these transformations generally proceeds via stepwise heterolytic of the E-H (Si-H or B-H) by the FLP, generating a cationic silylium or boryl paired with a anion. This activated pair then undergoes insertion of the unsaturated (carbonyl, , or arene C-H), followed by migratory transfer of the to complete the and regenerate the catalyst. For Si-H , the equation can be represented as: \text{FLP} + \ce{R3Si-H} \rightarrow [\text{FLP-H}^-][\ce{R3Si}^+] \rightarrow \text{product + FLP} This pathway parallels hydride delivery in FLP hydrogenation but substitutes silicon or boron for hydrogen in the reduction step.

Other Catalytic Transformations

Frustrated Lewis pairs (FLPs) have enabled metal-free catalytic reductions of CO₂ to and through hydride shuttle mechanisms, particularly in post-2015 developments integrating FLPs into metal-organic frameworks (MOFs). In UiO-66 frameworks functionalized with intramolecular FLPs, such as those featuring and sites, CO₂ hydrogenation proceeds via a stepwise pathway involving hydride transfer to the carbon of CO₂ followed by of an oxygen atom, yielding with low activation barriers around 21 kcal/mol and favorable thermodynamics (ΔG ≈ 6 kcal/mol). These systems enhance production by approximately 200-fold compared to gas-phase reactions at 298 K and 60 bar, due to confinement effects that increase local density and selectively adsorb the product per . For formation, adamantane-based phosphine-borane FLPs facilitate CO₂ in three steps, reducing activation barriers by ~6 kcal/mol relative to phenylene analogs, thanks to reduced steric strain and improved Lewis acid/base interactions in a gauche conformation. FLPs also serve as initiators in by precatalysts to generate . A 2024 study demonstrated that the FLP comprising 2,6-lutidine and B(C₆F₅)₃ deprotonates methyltrioxorhenium (MTO), forming a rhenium-methylidene that catalyzes ring-opening metathesis of and cross-metathesis of internal olefins under mild conditions. This avoids strong formation, allowing the Lewis base to abstract a proton while the stabilizes the conjugate acid, with rhenium-alkylidene intermediates confirmed by ESI-MS; catalyst deactivation via over-deprotonation to a methylidyne can be reversed by reprotonation. In C-H activation for arene functionalization, FLPs from the 2020s have advanced metal-free borylation and protocols. Zinc cation/ FLPs catalyze heteroarene C-H borylation with (PinBH), expanding scope to substrates like via (SᴱAr) mechanisms involving arenium intermediates and H₂ evolution, achieving high and yields up to 90%. Similarly, borenium/ FLPs enable silylation of unactivated arenes such as using H₂SiArᴺ₂ (Arᴺ = 2,4,6-trifluorophenyl), proceeding through a silylium intermediate for C-H activation without sacrificial acceptors, as verified by kinetic isotope effects and X-ray characterization of the key species. These approaches highlight FLPs' role in generating electrophilic main-group species for direct arene C-H cleavage, with 2025 examples extending to functionalization. FLPs initiate of isobutene by activating the to form chains. Intramolecular Al/P FLPs, such as those with cationic aluminum centers, coordinate isobutene via weak interactions, promoting C-H activation and generation that propagates chain growth, yielding polyisobutylene with controlled molecular weights. This metal-free strategy leverages steric frustration to avoid quenching, enabling living characteristics observed in related systems.

Broader Applications

Carbon Capture and Utilization

Frustrated Lewis pairs (FLPs) enable reversible of CO₂ through the cooperative interaction of sterically hindered , forming zwitterionic s that can be dissociated under mild conditions such as heating or . Intramolecular FLPs, such as those featuring phosphine-borane linkages (e.g., o-(tBu₂P)C₆H₄B(C₆F₅)₂), typically bind one equivalent of CO₂ per acid-base pair, achieving capacities up to 1 mol CO₂ per mol of FLP, with release possible at temperatures around 80°C under . This reversibility stems from the weak Lewis acid-oxygen and Lewis base-carbon bonds in the , allowing for efficient capture without permanent . In CO₂ utilization, FLPs catalyze hydrogenation reactions to produce value-added chemicals like and , often employing external reductants such as H₂, (e.g., 9-BBN or HBcat), or silanes (e.g., Et₃SiH). For production, main-group FLP systems such as amine/B(C₆F₅)₃ pairs reduce CO₂ with silanes to derivatives under ambient conditions. synthesis proceeds via sequential reduction steps, as in the phosphine-mediated pathway using tBu₃P/9-BBN, which yields with a TON of 5556 and TOF of 176 h⁻¹ after of intermediates. These processes can be cycled multiple times by regenerating the active FLP species, though external reductant addition is required for sustained operation. Advances from 2018 to 2025 have focused on supported FLPs to enable continuous CO₂ capture and integrated utilization, enhancing practicality for applications. Silica-supported intermolecular FLPs, such as Mes₃B/P(tBu)₃, capture CO₂ and facilitate conversion to , with TONs exceeding 100. Heterogeneous systems, including FLP-functionalized metal-organic frameworks (MOFs) like UiO-67-B(CH₃)₂, promote CO₂ to with improved H₂ activation and selectivity up to 90%, demonstrating TONs over 1000. Polymeric FLPs have achieved even higher efficiencies, with TONs up to 14,800 for CO₂-derived formamides, underscoring their potential for scalable, recyclable catalysis. Recent developments include photoactive surface FLPs on for efficient CO₂ capture and activation as of December 2024. Despite these progresses, challenges persist in achieving industrial scalability and efficient regeneration under mild conditions. Strong binding affinities in some FLP-CO₂ adducts complicate product release without energy-intensive processes, limiting cycle efficiency to fewer than 10 turnovers in unsupported systems. Moreover, deactivation due to side reactions with or impurities hinders long-term , necessitating further optimization of support materials and steric designs for broader adoption in sustainable carbon management.

Emerging Uses in Synthesis

Frustrated Lewis pairs (FLPs) have found emerging applications in the synthesis of pharmaceuticals, particularly through metal-free C-N bond-forming processes that generate chiral as key intermediates. Chiral FLPs catalyze the enantioselective of imines to produce primary and secondary with high enantioselectivity, often exceeding 90% ee under mild conditions such as ambient and pressure. This approach avoids metals, reducing and cost in manufacturing, and has been applied to synthesize enantioenriched amine building blocks relevant to pharmaceutical scaffolds like β-adrenergic antagonists. For instance, sterically encumbered borane-phosphine FLPs derived from binaphthyl frameworks enable asymmetric of cyclic imines, yielding products that serve as precursors in alkaloid-inspired structures. In materials , FLPs initiate reactions to form porous polymers with integrated catalytic sites, offering advantages in heterogeneous platforms. Intramolecular B/N FLPs incorporated into porous aromatic frameworks (PAFs) facilitate the controlled assembly of high-surface-area materials (>1000 m²/g) suitable for selective transformations. These polymers leverage the cooperative Lewis acid-base reactivity to trigger ring-opening polymerizations of cyclic ethers, producing self-healing gels or networks with tunable mechanical properties for advanced synthetic applications. The metal-free nature allows for sustainable production of porous sorbents that can be recycled multiple times without loss of activity, enhancing efficiency in scalable materials . Recent developments from to 2025 highlight bio-inspired FLPs mimicking active sites for C-C coupling in . Chiral FLPs embedded in metal-organic frameworks (MOFs) create confined microenvironments that emulate enzymatic selectivity, enabling asymmetric C-C bond formation via or cross-coupling with up to 99% . For example, a study demonstrated an intramolecular P/B FLP in a MOF catalyzing regioselective C-C bond formation in allylic substrates under mild aqueous conditions, inspired by natural aldolases. These systems provide metal-free alternatives to traditional Pd-catalyzed couplings, with case studies showing their use in constructing polycyclic frameworks akin to alkaloids, such as in the of derivatives where FLP-mediated reduction and subsequent C-C yield complex analogs in >80% overall yield. The mild, ambient conditions and high stereocontrol underscore FLPs' potential to streamline multi-step syntheses while minimizing environmental impact.

Related Phenomena

Frustrated Radical Pairs

Frustrated radical pairs (FRPs) represent an extension of frustrated Lewis pair (FLP) chemistry, where steric hindrance prevents the recombination of s generated through single-electron (SET), leading to persistent radical states that enable unique reactivity. In to classical FLPs, which typically involve two-electron heterolytic processes, FRPs arise from homolytic or SET events, maintaining the radicals in close proximity yet separated by bulky substituents. This frustration stabilizes the open-shell , analogous to how steric bulk in FLPs inhibits dative formation in ionic mechanisms. FRPs can be generated through various methods, including photoexcitation of electron donor-acceptor (EDA) complexes or processes involving external reductants. For instance, of intramolecular phosphine-borane FLPs with visible (λ = 400–800 nm) induces SET, producing persistent B•/P• pairs such as [Mes₃P]•⁺/[B(C₆F₅)₃]•⁻, where mesityl and pentafluorophenyl groups provide the necessary steric separation. Another pathway involves FLP-mediated homolysis of H₂, as demonstrated with reduced Lewis acidic like tris(3,5-dinitromesityl), which form radical anions that cleave H₂ into sterically separated H• and [B-H]• pairs upon exposure to reductants such as Cp*₂Co. These processes are supported by (EPR) spectroscopy, which detects characteristic signals for the radical intermediates, confirming their stability at low temperatures. The reactivity of FRPs diverges from ionic FLP pathways by enabling one-electron radical processes, such as additions to unsaturated substrates. For example, B•/P• pairs add to alkenes via mechanisms, facilitating site-selective C–H functionalizations that are inaccessible through two-electron heterolysis. This radical character allows for or dioxygenation of alkenes, where the separated radicals interact sequentially with the π-system rather than via concerted polar cleavage. Research from 2019 to 2025 has expanded applications, particularly in , leveraging their persistent nature for controlled material synthesis. Photoinduced polymeric FRPs (poly(s)), generated in situ from FLP-containing monomers under blue LED irradiation (λ_max = 455 nm), serve as building blocks for photocatalytic perfluoroalkylations and hydrogenations, with evidence (g = 2.0050 for B• anions; A_iso = 702 MHz for P• cations) verifying the radical pairs at 20 K. These developments highlight FRPs' potential in , distinct from traditional FLP , though debates persist on distinguishing SET from two-electron pathways in some activations.

Extensions to Non-Classical Systems

The concept of frustrated Lewis pairs (FLPs) has been extended beyond traditional main-group elements to all-carbon systems, where sterically hindered carbenium ions serve as Lewis acids and ylides or as bases, enabling small-molecule without heteroatom involvement. A seminal example involves the combination of the trityl cation (Ph₃C⁺) as the Lewis acid and the bulky N-heterocyclic 1,3-di-tert-butylimidazolin-2-ylidene (ItBu) as the base, forming an all-carbon FLP capable of heterolytically splitting H₂ at low temperatures around -60 °C, yielding the protonated and . This 2011 report by Arduengo and coworkers demonstrated the viability of carbon-only FLPs for H₂ , highlighting their potential in metal-free despite challenges in stability and reversibility. Subsequent studies have explored similar carbenium/ pairs for CO₂ capture and other activations, building on the core FLP principles of steric frustration to prevent formation. Heterogeneous FLPs represent another extension, immobilizing Lewis acid and base sites on solid supports to create reusable catalysts while maintaining the cooperative reactivity of molecular FLPs. Silica-supported FLPs, for instance, have been developed by grafting acids and bases onto mesoporous silica surfaces, enabling efficient Z-selective of alkynes under mild conditions without transition metals; these systems exhibit high turnover numbers and recyclability over multiple runs due to the high surface area and site isolation provided by the support. Similarly, metal-organic frameworks (MOFs) such as UiO-66 have been functionalized with boron-based acids and nitrogenous bases to form intraparticle FLPs, facilitating CO₂ to with enhanced stability and selectivity compared to homogeneous counterparts, as the porous structure prevents aggregation and leaching. These heterogeneous variants, reviewed in 2020, offer practical advantages for industrial applications by combining FLP chemistry with the durability of solid-state materials, though remains a challenge. Ambiphilic molecules integrate both Lewis acid and base functionalities within a single framework, creating intramolecular FLPs that exhibit enhanced robustness and selectivity in small-molecule activation. These systems leverage the fixed spatial arrangement of acid-base sites to lower activation barriers for reactions like O-H bond cleavage, outperforming intermolecular FLPs in terms of efficiency and resistance to decomposition. Further designs, such as amine-borane hybrids, have expanded ambiphilic FLPs to catalytic reductions of carbonyls, emphasizing the role of intramolecular frustration in enabling cooperative reactivity. Looking toward future directions, FLP concepts are being integrated into electrochemistry and photochemistry to harness external stimuli for controlled activation. In electrochemistry, a 2025 study utilized borane clusters (B₁₀H₈²⁻) paired with ammonium cations as an FLP in electric double layers at Au(111) electrodes, where applied potentials gate the pair's formation, shifting boron cluster electronics to enhance electron transport and enable reversible single-molecule switching for potential sensor applications. In photochemistry, alkene-protected FLPs were developed in 2024, where UV irradiation uncages the acid-base pair to activate H₂ in situ, offering light-triggered catalysis with high spatiotemporal control and compatibility with photochemical reactors for sustainable synthesis. These advancements, exemplified by 2024-2025 reports, suggest FLPs could enable stimulus-responsive systems in energy conversion and green chemistry.

References

  1. [1]
    Frustrated Lewis Pairs: From Concept to Catalysis - ACS Publications
    Dec 23, 2014 · Frustrated Lewis pair (FLP) chemistry has emerged in the past decade as a strategy that enables main-group compounds to activate small molecules.Introduction · Stoichiometric Heterolytic H2... · Catalytic Hydrogenations · Biography
  2. [2]
    Insights into Single-Electron-Transfer Processes in Frustrated Lewis ...
    Jul 11, 2023 · A review. This review summarizes the principle reaction mechanisms of frustrated Lewis pairs (FLP) in hydrogenations and carbon-nitrogen and ...
  3. [3]
    Frustrated Lewis Pairs | Journal of the American Chemical Society
    Jul 27, 2015 · Frustrated Lewis pairs have been used to activate a variety of small mols. In this review we focus on the recent chem. of FLPs with CO2, CO, N2O ...Introduction · FLP Chemistry of Small... · FLP Chemistry: In Context
  4. [4]
    Frustrated Lewis Pair Chemistry: Development and Perspectives
    May 14, 2015 · Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in solution that are deterred from strong adduct formation by ...
  5. [5]
    Reversible, Metal-Free Hydrogen Activation - Science
    Nov 17, 2006 · Redox‐Active Frustrated Lewis Pair‐Mediated B─H Bond Activation: From Proton Transfer to THF Ring Opening, ChemistryEurope, (2025).https ...Missing: paper | Show results with:paper
  6. [6]
    Tuning Lewis acidity using the reactivity of “frustrated Lewis pairs”
    The concept of “frustrated Lewis pairs” involves donor and acceptor sites in which steric congestion precludes Lewis acid–base adduct formation.
  7. [7]
    Frustrated Lewis Pairs: Metal‐free Hydrogen Activation and More
    Dec 22, 2009 · Frustrated Lewis pairs are inter- or intramolecular combinations of bulky phosphines or amines with strongly electrophilic RB(C 6 F 5 ) 2 components.
  8. [8]
    Frustrated Lewis Pairs: Bonding, Reactivity, and Applications
    May 9, 2023 · This Review explores the use of frustrated Lewis pairs (FLPs) in catalysis, with a focus on small molecule activation and associated ...
  9. [9]
    An easy-to-perform evaluation of steric properties of Lewis acids
    Feb 6, 2023 · The evaluation uses percent buried volume (%VBur) on fluoride adducts and the LAB-Rep model to assess steric properties of Lewis acids.
  10. [10]
    Parallels between Metal‐Ligand Cooperativity and Frustrated Lewis ...
    Apr 17, 2019 · We have shown that FLP and MLC chemistry both involve the cooperative action of a Lewis acid and a Lewis base, and that steric control to ...
  11. [11]
    Experimental Insights into the Structure and Reactivity of Frustrated ...
    Dec 2, 2014 · This review focuses mainly on the experimental studies of both the structure and reactivity of FLPs providing a starting body of evidence to ...
  12. [12]
    https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejic.201900169
  13. [13]
    Metal-Free Catalytic Hydrogenation of Polar Substrates by ...
    In 2006, our group reported the first metal-free systems that reversibly activate hydrogen. This finding was extended to the discovery of “frustrated Lewis ...
  14. [14]
    Moisture-Tolerant Frustrated Lewis Pair Catalyst for Hydrogenation ...
    Jul 31, 2015 · In this paper, we report on the development of a bench-stable borane for frustrated Lewis pair catalyzed reduction of aldehydes, ketones, and enones.
  15. [15]
    A chiral borane catalyzed asymmetric hydrosilylation of imines
    An enantioselective hydrosilylation of imines was successfully achieved using a chiral borane catalyst generated by the in situ hydroboration of a ...Missing: FLP | Show results with:FLP
  16. [16]
    Asymmetric catalysis with FLPs - RSC Publishing
    Nov 14, 2023 · This review provides an overview of the remarkable progress made in this field over the past 15 years. The design and synthesis of chiral FLPs ...
  17. [17]
    On the concept of frustrated Lewis pairs - Journals
    Jul 24, 2017 · The term 'frustrated Lewis pair' was coined in 2007 [9], a year after the finding that Mes2P(C6F4)B(C6F5)2 reacted reversibly with molecular ...Missing: milestones | Show results with:milestones
  18. [18]
    Alternative Pathway of CO2 Hydrogenation by Lewis-Pair ...
    May 1, 2020 · The reaction between H 2 and CO 2 catalyzed by an intramolecular frustrated Lewis pair, which is covalently bonded to a UiO-66 metal–organic framework (MOF), ...
  19. [19]
    Enhancement of formic acid production from carbon dioxide ...
    Jul 1, 2023 · In a study by Yang and Jiang [70] , the defective UiO-66 with a frustrated Lewis pair was successfully used in a three-stage transformation of ...
  20. [20]
    Exploring the metal-free catalytic reduction of CO2 to methanol with ...
    The reduction of CO2 into methanol via hydroboration reaction using the unsaturated phenylene scaffold contained frustrated Lewis pair, 1-Bcat-2-PPh2-C6H4 (I) ...Missing: post- | Show results with:post-
  21. [21]
    Activation of Methyltrioxorhenium for Olefin Metathesis by a ...
    Nov 21, 2024 · Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in soln. that are deterred from strong adduct formation by steric ...
  22. [22]
    C─H Silylation of Unactivated Arenes Catalyzed by a Borenium/Pyridine Lewis Pair
    ### Summary of FLP Catalyzed C-H Silylation of Unactivated Arenes
  23. [23]
    Main Group Catalyzed Arene Borylation: Challenges and ...
    May 23, 2023 · C–H borylation is an efficient method to generate organoboranes that are powerful intermediates in synthesis, due in large part to the ...The Importance of [H]+ · Approach (i) Arene C–H... · Approach (ii) Arene C–H...
  24. [24]
    A Frustrated Lewis Pair Based on a Cationic Aluminum Complex ...
    Jan 8, 2016 · We anticipate that enforcing a greater degree of steric frustration ... frustrated Lewis pairs with azides and a diazomethane – formation of ...
  25. [25]
    https://pubs.acs.org/doi/10.1021/jacs.4c12888
  26. [26]
    https://onlinelibrary.wiley.com/doi/10.1002/ange.202520852
  27. [27]
    https://pubs.acs.org/doi/10.1021/acscatal.3c01668
  28. [28]
    Article Readily accessible chiral frustrated Lewis pair catalysts
    Apr 18, 2024 · Although frustrated Lewis pair (FLP) chemistry has found numerous applications, FLPs are best known for their utility in catalytic, metal-free ...
  29. [29]
    Engineering Frustrated Lewis Pair Active Sites in Porous Organic ...
    May 30, 2024 · The frustrated Lewis pair (consisting of Na+H- and O(H+)) generated within zeolite NaY may be a useful catalyst for various catalytic reactions ...
  30. [30]
    Cyclic Ether Triggers for Polymeric Frustrated Lewis Pair Gels - PMC
    Cyclic ethers trigger polymer network formation in macromolecular FLPs, where the network's properties are tuned by the ether's properties.
  31. [31]
    Porous frustrated Lewis pair catalysts: Advances and perspective
    Mar 17, 2022 · This perspective summarizes recent progresses and provides an outlook in designing porous FLP catalysts for applications in heterogeneous catalysis.
  32. [32]
    Incorporation of Chiral Frustrated Lewis Pair into Metal–Organic ...
    Jul 27, 2023 · The incorporation of a chiral frustrated Lewis pair into a metal−organic framework with a tailored microenvironment creates enzyme-mimic regions ...Figure 3 · Figure 4 · Methods<|separator|>
  33. [33]
    C sp 2 Cross-Coupling Reactions Using Frustrated Lewis Pairs
    Mar 15, 2021 · Frustrated Lewis pair (FLP) chem. enables a rare example of alkyne 1,2-hydrocarbation with N-methylacridinium salts as the C Lewis acid. This 1, ...
  34. [34]
    Frustrated Radical Pairs: Insights from EPR Spectroscopy
    Sep 15, 2020 · Frustrated Radical Pairs: Insights from EPR Spectroscopy ... N,N-cycloaddition of C2-bridged intramolecular P/B frustrated Lewis pairs with nitric ...
  35. [35]
    A New Mode of Chemical Reactivity for Metal‐Free Hydrogen ...
    Apr 9, 2019 · ... frustrated Lewis pairs (FLPs). Instead of a Lewis base we use a ... This radical-based, redox pathway involves the homolytic cleavage ...
  36. [36]
    Frustrated Radical Pairs in Organic Synthesis - PMC - NIH
    Originally discovered during the studies of canonical frustrated Lewis pairs, the concept of frustrated radical pairs has begun to show promise as a new way to ...
  37. [37]
    Light-Induced Polymeric Frustrated Radical Pairs as Building Blocks ...
    Oct 27, 2023 · Polymeric frustrated Lewis pairs, or poly(FLP)s, have served to bridge the gap between functional polymer science and main group catalysis, ...Introduction · Results and Discussion · Conclusions · ReferencesMissing: isobutene | Show results with:isobutene
  38. [38]
    Heterogeneous Frustrated Lewis Pair Catalysts: Rational Structure ...
    Jan 28, 2025 · We have explored systematic characterization techniques to unravel the underlying mechanisms between the active sites and reactants.
  39. [39]
    Heterogeneous Catalysis by Frustrated Lewis Pairs - ResearchGate
    This includes supporting the Lewis acid and/or base components on or within a whole host of different materials, including silica, zeolites, metal-organic ...
  40. [40]
    https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202010633
  41. [41]
    Synthesis and Photochemical Uncaging of Alkene-Protected ...
    Aug 26, 2024 · ... Frustrated Radical Pairs” (FRPs). (55) Unlike FLP 1 and other ... Solid Molecular Frustrated Lewis Pairs in a Polyamine Organic ...