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This feature article examines some of the recent advances in the chemistry of Z-type transition metal–borane and X-type transition metal–boryl complexes. It focuses on the employment of these boron-based functionalities acting as stores and transfer agents for functional groups such as hydrides, alkyl groups and aryl groups which can either be abstracted or delivered to the metal centre. The review also explores the rather novel reactivity involving the cleavage of H–H, E–H and E–E′ bonds (where E and E′ are a range of groups) across the transition metal–boron bond in such complexes. It explores the early examples of the addition of H–H across transition metal–borane bonds and describes the new transformation in the context of other known modes of hydrogen activation including classic oxidative addition and heterolytic cleavage at transition metal centres as well as Frustrated Lewis Pair chemistry. Similar reactivity involving transition metal–boryl complexes are also described particularly those which undergo both boryl-to-borane and borane-to-borohydride transformations. The delivery of hydride to the metal centre in combination with the potential to regenerate the borohydride functional group via a recharging process is explored in the context of providing a new strategy for catalysis. Finally, a light-hearted look at the analogy of the ‘stinging processes’ involving Trofimenko type ligands is taken one step further to determine whether it is indeed in the nature of scorpionate ligands to repeatedly ‘sting’ just as the real life scorpions do.

A metal-free and efficient approach to N-aryl-substituted azacycles from arylamines and cyclic ethers is described. In this synthesis, the synergistic effect between Lewis and Bronsted acids is crucial to the ring-opening of cyclic ethers and the subsequent cyclization. The use of B(C6F5)3 enabled the formation of frustrated Lewis pairs (FLPs) from the reactants, and the resulting FLPs allowed ready access to the N-arylazacycles in moderate to good yields via further cyclization. Water is the sole waste resulting from the reaction, thereby making it an environmentally benign process.

While the organotrifluoroborate group is commonly used as a leaving group in cross-coupling reactions, we now show that their high stability can be used to protect the Lewis acidic moieties of frustrated Lewis pair catalysts. Indeed, the air and moisture-stable trifluoro- and difluoroborate derivatives of bulky (tetramethylpiperidino)benzene are shown to be conveniently converted to their dihydroborane analogue which is known to activate small molecules. An efficient synthesis route to these stable and convenient precatalysts, their deprotection chemistry and their benchtop use for the dehydrogenative borylation of heteroarenes is presented.

A highly enantioselective hydrosilylation of 1,2-dicarbonyl compounds was successfully realized for the first time utilizing the combination of tricyclohexylphosphine and chiral alkenylborane derived in situ from diyne as a frustrated Lewis pair catalyst. A variety of optically active α-hydroxy ketones and esters were obtained in 52–98% yields with 86–99% ee’s.

The potential of NMR spectroscopy to investigate inorganic systems assembled by, or whose reactivity is affected by, non-covalent interactions is described. Subjects that have received particular attention in recent years (halogen bonding and Frustrated Lewis Pairs) and more classical subjects that remain under-explored (self-aggregation of ion pairs in low polar solvents, behavior of MAO containing metallocenium ion pairs, and hydrogen bonding/ion pairing effects in Au(I) catalysis) are considered, using an innovative approach, always focusing on the crucial information that can be provided by NMR.

Part of the renaissance in main group chemistry has been a result of the focus on reactivity. This has led to the development of applications in stoichiometric reactivity and catalysis. In this tutorial review, we focus attention on the role of phosphorus-based Lewis acids in such advances. While early literature recognizes the role of P(III) and P(V) electrophiles in coordination chemistry, it has generally been more recent studies that have focused on applications of this Lewis acidity. Applications of these novel P-based Lewis acids in stoichiometric reactivity, Lewis acid catalysis and frustrated Lewis pair (FLP) reactivity are reviewed. These advances demonstrate that P-based Lewis acids are a powerful tool for further developments in metal-free catalysis.

Methyl abstraction from neutral [Cp2ZrMe(ERR′)] complexes 1 (E = N, P; R, R′ = alkyl, aryl) with either B(C6F5)3 or [Ph3C][B(C6F5)4] results in the formation of [Cp2Zr(ERR′)][X] complexes 2 (X– = MeB(C6F5)3–, B(C6F5)4–). The X-ray structure of amido complexes [Cp2Zr(NPh2)][MeB(C6F5)3] (2d) and [Cp2Zr(NtBuAr)][B(C6F5)4] (2e′, Ar = 3,5-C6H3(CH3)2) is reported, showing a sterically dependent Zr/N−π interaction. Complexes 2 catalyze the hydrogenation of electron-rich olefins and alkynes under mild conditions (room temperature, 1.5 bar H2). Complex 2e binds CO2, giving [Cp2Zr(CO2)(NtBuAr)]2[MeB(C6F5)3]2 (3e). Amido complex 2d reacts with benzaldehyde yielding [Cp2Zr(OCH2Ph)((OC)PhNPh2)][MeB(C6F5)3] (7d). Phosphido complex [Cp2Zr(PCy2)][MeB(C6F5)3] (2a) reacts with diphenylacetylene to yield frustrated Lewis pair [Cp2Zr(PhCCPh)(PCy2)][MeB(C6F5)3] (8a) which further reacts with a range of carbonyl substrates.

The hydrogenation of olefins is achieved using a combination of phoshorous(V)-based Lewis acids with diaryl amines for the activation of dihydrogen.

Frustrated Lewis pairs (FLPs) based on sterically encumbered anilines and the Lewis acid B(C6F5)3 were found to react with terminal alkynes effecting intermolecular hy- droamination affording iminium alkynylborate species of the form (RPhN=C(R')Me)(R'CCB(C6F5)3). In these cases, the re- agent ratio of borane, aniline, and alkyne is 1:1:2. These reac- tions could also be performed in an intramolecular fashion by using anilines with alkynyl substituents effecting cycliza- tion reactions. The use of 10 mol % B(C6F5)3 under a H2 at- mosphere provides a one-pot synthesis of the pyrrolidine 12, the piperidines 13-15, the azepane 16, the isoindoline 17, and the benzoxazine 18.

A series of ketones and aldehydes are reduced in toluene under H2 in the presence of 5 mol % B(C6F5)3 and either cyclodextrin or molecular sieves affording a facile metal-free protocol for reduction to alcohols. Similar treatment of aryl ketones resulted in metal-free deoxygenation yielding aromatic hydrocarbons.

The articulation of the notion of “frustrated Lewis pairs” (FLPs), which emerged from the discovery that H2 can be reversibly activated by combinations of sterically encumbered Lewis acids and bases, has prompted a great deal of recent activity. Perhaps the most remarkable consequence has been the development of FLP catalysts for the hydrogenation of a range of organic substrates. In the past 9 years, the substrate scope has evolved from bulky polar species to include a wide range of unsaturated organic molecules. In addition, effective stereoselective metal-free hydrogenation catalysts have begun to emerge. The mechanism of this activation of H2 has been explored, and the nature and range of Lewis acid/base combinations capable of effecting such activation have also expanded to include a variety of non-metal species. The reactivity of FLPs with a variety of other small molecules, including olefins, alkynes, and a range of element oxides, has also been developed. Although much of this latter chemistry has...

The advent of frustrated Lewis pair (FLP) chemistry almost a decade ago was based on the reactivity of sterically encumbered combinations of electrophilic boranes and phosphines with hydrogen. Sinc...

The interaction of a Lewis acid with a Lewis base results in the formation of a Lewis acid base adduct. Understanding Lewis acids and bases is central to conceptualizing chemical interactions and constitutes a major portion of metal ligand chemistry. Sterically encumbered/constrained Lewis pairs cannot form acid-base adducts, but such `Frustrated Lewis Pairs' (FLPs), with their unquenched electronic demands can be elegantly used to simultaneously react with a third species, resulting in unusual reactivity of small molecules. Such unusual reactions, explored only in the last few years, have found several applications, e.g., heterolytic splitting of H-2, activation of small molecules (CO2, N2O, etc.). FLPs have opened new opportunities in synthetic chemistry, covering organic, main group as well as transition metal chemistry. The design strategies adopted for FLP systems and their unique reactivity are discussed here.

Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in solution that are deterred from strong adduct formation by steric and/or electronic factors. This opens pathways to novel cooperative reactions with added substrates. Small-molecule binding and activation by FLPs has led to the discovery of a variety of new reactions through unprecedented pathways. Hydrogen activation and subsequent manipulation in metal-free catalytic hydrogenations is a frequently observed feature of many FLPs. The current state of this young but rapidly expanding field is outlined in this Review and the future directions for its broadening sphere of impact are considered.

The strong boron Lewis acid tris(pentafluorophenyl)borane, B(C6F5)3, is shown to abstract a hydride from suitably donor-substituted cyclohexa-1,4-dienes, eventually releasing dihydrogen. This process is coupled with the FLP-type (FLP = frustrated Lewis pair) hydrogenation of imines and nitrogen-containing heteroarenes that are catalyzed by the same Lewis acid. The net reaction is a B(C6F5)3-catalyzed, i.e., transition-metal-free, transfer hydrogenation using easy-to-access cyclohexa-1,4-dienes as reducing agents. Competing reaction pathways with or without the involvement of free dihydrogen are discussed.

In this simple metal-free procedure borane and ether behave as a frustrated Lewis pair to activate H2 and effect the reduction of ketones.

The ability to bind CO2 through the formation of low-energy, easily-broken, bonds could prove invaluable in a variety of chemical contexts. For example, weak bonds to CO2 would greatly decrease the cost of the energy-intensive sorbent-regeneration step common to most carbon capture technologies. Furthermore, exploration of this field could lead to the discovery of novel CO2 chemistry. Reduction of complexed carbon dioxide might generate chemical feedstocks for the preparation of value-added products, particularly transportation fuels or fuel precursors. Implementation on a large scale could help to drastically reduce CO2 concentrations in the atmosphere. However, literature examples of weakly bonded complexes of CO2 are relatively few and true coordination complexes to a ‘naked’ CO2 fragment are nearly unheard of. In this review article, a variety of complexes of CO2 featuring diverse binding modes and reactivity will be examined. Topics covered include: (A) inclusion complexes of CO2 in porous materials. (B) Zwitterionic carbamates produced from the reaction of CO2 with polyamines. (C) Carbamate salts produced from reaction of CO2 with two equivalents of an amine. (D) Insertion products of CO2 into acid-base adducts (e.g., metal complexes). (E) Lewis acid–base activated CO2, such as frustrated Lewis pair complexes. (F) Simple base–CO2 adducts, wherein the base–CO2 bond is the only interaction formed. Complexes in the last category are of particular interest, and include imidazol-2-carboxylates (N-heterocyclic carbene adducts of CO2) as well as a few other examples that lie outside NHC chemistry.

Frustrated Lewis pairs (FLPs), namely the combination of a Lewis acid (LA) and a Lewis base (LB) that cannot fulfil their natural propensity to form stable Lewis adducts, have been recently exploited to activate small molecules, such as H2 and CO2, and have drawn much interest, due to their applicability in metal-free catalytic reactions. This review focuses mainly on the experimental studies of both the structure and reactivity of FLPs providing a starting body of evidence to elucidate the mechanism of their action. Important insights coming from NMR spectroscopy, X-ray diffraction and other experimental techniques are highlighted and discussed. In particular, evidence about the tendency of LA and LB to interact in the absence of a substrate are commented on for both inter- and intramolecular FLPs, underlining the role played by the structure of LA and LB in determining the level of interaction. Next, the effect of the structure of FLPs on the kinetics and thermodynamics of substrate activation is illustrated, with a particular focus on catalytic hydrogenation reactions.

CONSPECTUS: Frustrated Lewis pair (FLP) chemistry has emerged in the past decade as a strategy that enables main-group compounds to activate small molecules. This concept is based on the notion that combinations of Lewis acids and bases that are sterically prevented from forming classical Lewis acid-base adducts have Lewis acidity and basicity available for interaction with a third molecule. This concept has been applied to stoichiometric reactivity and then extended to catalysis. This Account describes three examples of such developments: hydrogenation, hydroamination, and CO2 reduction. The most dramatic finding from FLP chemistry was the discovery that FLPs can activate H2, thus countering the long-existing dogma that metals are required for such activation. This finding of stoichiometric reactivity was subsequently evolved to employ simple main-group species as catalysts in hydrogenations. While the initial studies focused on imines, subsequent studies uncovered FLP catalysts for a variety of organic substrates, including enamines, silyl enol ethers, olefins, and alkynes. Moreover, FLP reductions of aromatic anilines and N-heterocycles have been developed, while very recent extensions have uncovered the utility of FLP catalysts for ketone reductions. FLPs have also been shown to undergo stoichiometric reactivity with terminal alkynes. Typically, either deprotonation or FLP addition reaction products are observed, depending largely on the basicity of the Lewis base. While a variety of acid/base combinations have been exploited to afford a variety of zwitterionic products, this reactivity can also be extended to catalysis. When secondary aryl amines are employed, hydroamination of alkynes can be performed catalytically, providing a facile, metal-free route to enamines. In a similar fashion, initial studies of FLPs with CO2 demonstrated their ability to capture this greenhouse gas. Again, modification of the constituents of the FLP led to the discovery of reaction systems that demonstrated stoichiometric reduction of CO2 to either methanol or CO. Further modification led to the development of catalytic systems for the reduction of CO2 by hydrosilylation and hydroboration or deoxygenation. As each of these areas of FLP chemistry has advanced from the observation of unusual stoichiometric reactions to catalytic processes, it is clear that the concept of FLPs provides a new strategy for the design and application of main-group chemistry and the development of new metal-free catalytic processes.

This feature article describes the chemistry in motion of frustrated Lewis pairs (FLPs). With state-of-the-art ab initio molecular dynamics (AIMD) simulations supplemented by minimum energy path (MEP) and potential energy surface (PES) calculations, we examine the binding of CO2 and the heterolytic cleavage of H-2 by a Lewis base (LB), tBu(3)P, and a Lewis acid (LA), B(C6F5)(3). We strive to uncover and understand mechanistic implications of the physical laws that govern the behavior of a LB and a LA when they react with a third species (e.g., CO2 or H-2) at finite temperature. The approximation that we necessarily must make at present is to forgo the quantization of the movement of atoms in favor of the Born-Oppenheimer molecular dynamics (BOMD), which unfold according to the classical (Newton's) laws of motion. However, strict quantum chemical theory is used to compute all of the forces that govern the dynamics of the macromolecular FLP system. Using physical reasoning and innovative computer simulations, we show that multi-scale motion is the predominant mechanistic aspect in reactions of the tBu(3)P/B(C6F5)(3) FLP, as well as, conceivably, those of other similar intermolecular FLPs. Insight achieved thus far leads to a novel activity model for intermolecular FLPs and specific predictions, which could be useful for future experimental and theoretical studies of FLP and other chemistries.

Frustrated Lewis pair (FLP) chemistry has provided a new strategy for small-molecule binding and/or catalytic activation. The most prominent FLPs are based on intramolecular phosphaneborane adducts, the catalytic properties of which can be tailored over wide ranges of reactivity and selectivity. Advanced solid-state NMR spectroscopic techniques, together with DFT calculations, can provide new structural insights in these systems. This review illustrates the utility of 31P and 11B NMR chemical shifts, 11B electric field gradient tensors, and 31P11B indirect and direct dipoledipole interactions for characterizing intramolecular boranephosphane FLPs. We demonstrate the potential of this method to 1) quantify the extent of boronphosphorus bonding interactions (and hence, the “degree of frustration”); 2) reveal specific structural details (i.e., boronphosphorus distances and other local geometric aspects) related to their catalytic activities; and (3) characterize products of FLP reactions with regard to molecular structure, stereochemistry, and aggregation properties in terms of internuclear distances, bonding connectivities, and orientational parameters.

An N-methylacridinium salt is successfully used as catalyst for the reduction of aldimines and the hydrosilylation of alcohols.

Bulky Lewis acids and Lewis bases do not undergo neutralization to form classical Lewis acid–base adducts because of steric hindrance. The Lewis acids and Lewis bases involved in this phenomenon are termed “frustrated Lewis pairs” (FLPs). The synergy between the unquenched acid and base endows the Lewis pair with the ability to activate small molecules, in particular hydrogen. A milestone discovery in this field was reported by Stephan and co-workers in 2006, in which a phosphine–borane compound was reported to reversibly activate hydrogen under mild conditions. Since then, FLP chemistry has developed into a cutting-edge concept. Most of the reported FLPs, generally based on the strong Lewis acid B(C6F5)3 accompanied by a bulky amine or phosphine, may serve as hydrogenation catalysts. Recently, metal-free hydrogenation using FLP catalysts has been regarded as a promising application of FLP chemistry. FLP catalytic systems are able to hydrogenate a wide range of unsaturated substrates, such as imines, enamines, enol ethers, and heterocycles. Enantioselective hydrogenation, which is still dominated by transition-metal catalysts, plays a pivotal role in organic synthesis. Considering the increasingly stringent limits on the amount of metal impurities found in drug compounds, the development of an effective metal-free catalyst for enantioselective hydrogenation to synthesize chiral molecules is a longterm challenge. FLP-type enantioselective hydrogenation is a rational extension of this hydrogenation chemistry owing to its significant potential for the transition-metal-free synthesis of chiral molecules. However, FLP-type catalytic enantioselective hydrogenation has remained relatively unexplored. This strategy is hampered by the design and synthesis of an effective chiral borane reagent because this class of air-sensitive compound cannot be purified by the usual chromatography techniques. Another issue confronting researchers is that the stereoselectivity of borane connected to the chiral scaffold through a single s bond is difficult to control because two perfluorophenyl groups are necessary to keep enough Lewis acidity for H2 activation. To realize FLP-type catalytic enantioselective hydrogenation, four kinds of chiral FLP catalysts can be considered (Scheme 1), mode I: chiral B moiety, achiral N(P) moiety; mode II : achiral B moiety, chiral N(P) moiety; mode III : intramolecular chiral FLP; mode IV: chiral B moiety, chiral N(P) moiety. Great progress has been made in the rational design of chiral FLP catalysts based on modes I–III in recent years, but mode IV remains to be explored (Figure 1). In mode I, the chiral B H species resulting from H2 activation is expected to undergo an asymmetric hydride transfer to proScheme 1. Enantioselective metal-free hydrogenation by means of an FLP strategy.

In recent years ‘frustrated Lewis pairs’ (FLPs) have been shown to be effective metal-free catalysts for the hydrogenation of many unsaturated substrates. Even so, limited functional-group tolerance restricts the range of solvents in which FLP-mediated reactions can be performed, with all FLP-mediated hydrogenations reported to date carried out in non-donor hydrocarbon or chlorinated solvents. Herein we report that the bulky Lewis acids B(C6Cl5)x(C6F5)3−x (x=0–3) are capable of heterolytic H2 activation in the strong-donor solvent THF, in the absence of any additional Lewis base. This allows metal-free catalytic hydrogenations to be performed in donor solvent media under mild conditions; these systems are particularly effective for the hydrogenation of weakly basic substrates, including the first examples of metal-free catalytic hydrogenation of furan heterocycles. The air-stability of the most effective borane, B(C6Cl5)(C6F5)2, makes this a practically simple reaction method.

The activation of H 2 for the catalytic hydrogenation of unsaturated compounds is one of the most useful reactions in both academia and chemical industry, which has long been predominated by the transition-metal catalysis. However, metal-free hydrogen activation represents a formidable challenge, and has been less developed. The recent emerging chemistry of frustrated Lewis pairs (FLPs) with a combination of sterically encumbered Lewis acids and Lewis bases provides a promising approach for metal-free hydrogenation due to their amazing abilities for the challenging H 2 activation. In the past several years, the hydrogenation of a wide range of unsaturated compounds using FLP catalysts has been successfully developed. Despite these advances, the corresponding asymmetric hydrogenation is just in its start-up step. Similar to the mode of H H bond activation, Si H bond can also be activated by FLPs for the hydrosilylation of ketones and imines. But its asymmetric version is also not well-solved. This Letter will outline the recent important progress of metal-free catalytic asymmetric hydrogenation and hydrosilylation using FLP catalysts.

Treatment of the analogue of (IV) without the methyl substituent leads to formation of the Lewis adduct as the only product.

A series of [2.2]paracyclophane-derived frustrated Lewis pairs (FLPs) with reversible, metal-free hydrogen activation was synthesized and successfully applied in the hydrogenation of imines in moderate to good yields. The high stability of the novel FLP system enables effective recycling of the metal-free catalysts. This reaction could also be compatible with a larger scale and developed into a pharmaceutical synthesis of cinacalcet {(R)-N-[1-(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine} without heavy metal residues.

One of the most important chemical transformations is the reduction of multiple bonds, carbon–carbon as well as carbon–heteroatom double bonds, since it leads very often to the generation of new stereocenters in the molecule. The replacement of metal-based catalysts with equally efficient metal-free counterparts is very appealing in view of possible future applications of non toxic, low cost, and environmentally friendly promoters on an industrial scale. This perspective will focus specially, but not exclusively, on the enantioselective reduction of the carbon nitrogen double bond; despite the historical need for and continued interest in chiral amines, their synthesis remains challenging. Three metal-free catalytic methodologies available for the reduction of carbon–nitrogen double bond will be discussed: i) binaphthol-derived phosphoric acids catalyzed reductions, with dihydropyridine-based compound as the reducing agent; ii) trichlorosilane mediated reductions, in the presence of catalytic amounts of chiral Lewis bases; iii) metal-free hydrogenation of imines through FLP (Frustrated Lewis Pair) methodology, that involves the use of a combination of a strong Lewis acid with a variety of sterically encumbered Lewis bases, for examples phosphines or tertiary amines, to activate hydrogen at ambient conditions. Special attention will be devoted to the most recent applications of the last five years.

Intramolecular vicinal and geminal frustrated Lewis pairs (FLPs) featuring bulky substituents at phosphorus or nitrogen and strongly electron-withdrawing bulky pentafluorophenyl substituents at boron undergo a variety of addition and/or activation reactions with small molecules. A number of examples of such reactions are presented and discussed, among them the FLP activation of dihydrogen to give zwitterionic phosphonium (or ammonium)/hydridoborate zwitterions. Intramolecular FLPs also add to organic carbonyl compounds (including carbon dioxide), to alkenes and alkynes (including conjugated dienes, diynes or enynes), to heterocumulenes, to azides, and to nitric oxide.

Hydrogen activation is a key step in hydrogenation reactions which are widely used in both laboratory synthesis and the chemical industry. Traditionally, it was often considered that only transition metal complexes/systems are able to activate hydrogen and to catalyze hydrogenations. This view has been changed recently; more and more metal-free molecules/systems have been found capable of activating hydrogen. Among these developments, the frustrated Lewis pairs (FLPs) are of particular significance, not only because they exhibit high reactivity toward hydrogen as well as other small molecules, but also because some of them can perform direct catalytic hydrogenations, which pave the way to the development of cheaper and greener hydrogenation catalysts. Inspired by the FLP principle, we used quantum mechanics computations to design molecules for H2, CH4, and NH3 activation and catalysts for hydrogenation of imines, ketones, and alkenes. While our designed molecules are awaiting experimental preparation, the active sites in our designed molecules anticipated the features appeared in the compounds synthesized later by experimentalists. This chapter reviews our computational explorations to enrich FLP chemistry.

The discovery of frustrated Lewis pairs is described, as well as the ability of these intermolecular systems to react with a range of small molecules.

The development and use of frustrated Lewis pairs (FLPs) as both stoichiometric and catalytic reductants for the hydrogenation of a variety of organic substrate is described.

Frustrated Lewis pair (FLP) chemistry has provided a new strategy for small molecule binding and/or catalytic activation. It is based on the cooperative reaction behavior of Lewis acid and Lewis base centers that are in close proximity to each other (e.g., within the same molecule) but cannot form a direct bond because of geometrical constraints. The most prominent FLPs are based on intramolecular phosphane–borane adducts, whose catalytic properties can be tailored over wide ranges of reactivity and selectivity. For the structural and chemical design of such systems, a fundamental understanding needs to be developed on how structure, dynamics and covalent interactions between the Lewis centers influence the reactivity profile. Advanced solid-state nuclear magnetic resonance (NMR) spectroscopic techniques afford new opportunities for addressing this challenge. Following a general introduction into the fundamentals of NMR spectroscopy, this review discusses the different types of internal interactions – magnetic shielding, nuclear electric quadrupolar coupling, indirect spin–spin interactions, and “through-space” dipole–dipole couplings – influencing NMR spectra in the solid state. As discussed in detail, each type of interaction bears specific informational content with regard to structural issues in FLP chemistry. One of the most attractive features of solid-state NMR is the possibility of tailoring the effective Hamiltonian by manipulations in either physical space or spin space. Using such “decoupling” or “recoupling” techniques certain types of interactions can be selectively turned off for spectral simplification or turned on for selective evaluation. The present review summarizes the most important selective averaging techniques that have found applications in the characterization of FLPs. In a second step the interaction parameters need to be connected with structure and bonding information. As illustrated in this chapter, ab initio calculations using density functional theory (DFT) methods have become indispensable for this task. Based on this comprehensive strategy including advanced NMR methodology, computer simulations, and ab initio calculations, the present review illustrates the utility of 31P and 11B NMR chemical shifts, 11B electric field gradient tensors, and 31P-11B indirect and direct dipole–dipole interactions for characterizing intramolecular borane–phosphane FLPs, illustrating the potential of this method to (1) quantify the extent of boron-phosphorus bonding interactions (and hence the “degree of frustration”) and (2) reveal specific structural details (i.e., boron–phosphorus distances and other local geometry aspects) relating to the catalytic activities of these exciting materials.

Computational studies that characterize the effects of Lewis acidity/basicity on FLP formation and reactivity are reviewed. Formation of the FLP encounter complex “cage” depends on Lewis acidities and basicities of substituent “external” atoms, and their abilities to interact intramolecularly. Computations indicate that these interactions are worth 9–18 kcal mol−1 for partly fluorinated FLPs such as (F5C6)3B···P(t-Bu)3, and less for less fluorinated species such as (H5C6)3B···P(t-Bu)3. Reactivity within the cage depends on the “classical” Lewis acidities/basicities of the internal atoms. Energetics here fall into the range of 5–50 kcal mol−1; the larger the value, the greater the ability of the FLP to capture or split a substrate. In several cases the computationally predicted reaction barriers differ little with internal Lewis acidity/basicity, indicating that the rate-determining step involves the substrate entering the cage rather than attack by the Lewis acid/base atoms. In others, barriers vary sizably with Lewis acidity/basicity, indicating the opposite. In one case it was shown that these effects cancel, such that the three component barriers are identical for a range of substituted Lewis acid FLP components.

Frustrated Lewis pairs have been used to activate a variety of small molecules. In this review we focus on the recent chemistry of FLPs with CO2, CO, N2O, NO and SO2. While FLP capture of these small molecule is achieved in all of these cases, subsequent applications of the products include stoichiometric and catalytic reductions of CO2, C–O bond scission of CO and use of FLP–NO radicals in polymerization.

Regioselective functionalizations of cinnoline at the 3 or 8 position are achieved using a frustrated Lewis pair (BF3·OEt2/Mg(Tmp)2·2LiCl) or in situ generated Zn(Tmp)2·2MgCl2·2LiCl, respectively.

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.

The intramolecular frustrated Lewis pair (FLP) Mes2PCH2CH2B(C6F5)2 4 adds cooperatively to carbon monoxide to form the five-membered heterocyclic carbonyl compound 5. The intramolecular FLP 7 contains an exo-3-B(C6F5)2 Lewis acid and an endo-2-PMes2 Lewis base functionality coordinated at the norbornane framework. This noninteracting FLP adds carbon monoxide in solution at -35 °C cooperatively to yield a five-membered heterocyclic FLP-carbonyl compound 8. In contrast, FLP 7 is carbonylated in a CO-doped argon matrix at 25 K to selectively form a borane carbonyl 9 without involvement of the adjacent phosphanyl moiety. The free FLP 7 was generated in the gas phase from its FLPH2 product 10. A DFT study has shown that the phosphonium hydrido borate zwitterion 10 is formed exergonically in solution but tends to lose H2 when brought into the gas phase.

Metal-free systems, including frustrated Lewis pairs (FLPs) have been shown to bind CO2. By reducing the Lewis acidity and basicity of the ambiphilic system, it is possible to generate active catalysts for the deoxygenative hydroboration of carbon dioxide to methanol derivatives with conversion rates comparable to those of transition-metal-based catalysts.

Review: progress in the development of new catalysts for the reduction of polar organisubstrates such as olefins, alkynes, and aromatic systems; 41 refs.

A straightforward and efficient alumination of functionalized arenes by using the frustrated Lewis pair Et3 Al and TMPMgCl⋅LiCl (TMP=2,2,6,6-tetramethylpiperidyl) has been developed. In particular, halogenated electron-rich aromatics can be smoothly functionalized by using the frustrated Lewis pair Et3 Al and TMPMgCl⋅LiCl. Compared with previously described alumination methods, this procedure avoids extensive cooling and the need for an excess of base. This in situ procedure has proven to be most practical and allows for regio- and chemoselective metalation of a wide range of aromatics with sensitive functional groups (CONEt2 , CO2 Me, CN, OCONMe2 ) or halogens (F, Cl, Br, I). The resulting aromatic aluminates, which were characterized by using NMR spectroscopy, were subjected to allylations, acylations, and palladium-catalyzed cross-coupling reactions after transmetalation to zinc. It was shown that the nature of the Zn salt used for transmetalation is crucial. Thus, compared with ZnCl2 (2 equiv), the use of Zn(OPiv)2 (2 equiv; OPiv=pivalate) allows the subsequent quenching reactions to be performed with only a slight excess of electrophile (1.2 equiv) and provides interesting functionalized aromatics in good yields.

Catalytic amounts of the Lewis acid B(C6 F5 )3 enable the hydroamination of terminal alkynes by aryl amines to the corresponding enamines. In accord with the results of stoichiometric reactions, the mechanism of this reaction involves a frustrated Lewis pair (FLP). The hydroamination can be followed by an FLP-catalyzed hydrogenation, resulting in a one-pot stepwise synthesis of amine derivatives.

An analysis of the metal-free reduction of electron deficient olefins by frustrated Lewis pairs indicates that the rate-determining step might be either the heterolytic cleavage of H2 to form an -onium borohydride salt, or the subsequent transfer of the hydride moiety to the substrate following a Michael-type addition reaction. While the use of strong Lewis acids such as B(C6F5)3 facilitates the first of these processes, hydride transfer to the olefin should be contrarily favoured by the use of weak Lewis acids which, for this very same reason, might be unable to promote the prior H2 split. After systematic testing of several boranes of different Lewis acidity (assessed by using the Childs' method) and steric demand, an optimal situation that employs tris(2,4,6-trifluorophenyl)borane was reached. Mixtures of this borane with 1,4-diazabicyclo[2.2.2]octane (DABCO) exhibited excellent catalytic activity for the hydrogenation of alkylidene malonates. In fact, this transformation could be achieved under milder conditions than those we reported previously. Moreover, the reaction scope could be expanded to other electron deficient olefins containing esters, sulfones or nitro functionalities as electron-withdrawing substituents.

Frustrated Lewis pair chemistry, in which solution phase combinations of Lewis acid Lewis base pairs (FLPs) act cooperatively to activate small molecules, is one of the most exciting recent developments in main group chemistry. Far less developed but of growing interest are FLP systems containing transition metals as one of the Lewis acid/base components. This Perspective reviews recent developments in this area and makes connections to existing research into cooperative and ligand assisted catalysis.

This review discusses the use of multidentate actor ligands as new inroads to small molecule activation and catalysis. Bio-inspired strategies such as the use of redox-active ligands, metal–ligand cooperation, and hemilabile ligands will be examined as they relate to functional actor ligands and their design. The application of new concepts of reactivity such as the use of frustrated Lewis pairs (FLPs) in actor ligand design will also be discussed. The focus of the discussion of metal–ligand cooperation will be on long-range cooperation between the metal and a remote reactive site on the ligand. In addition to metal–ligand cooperation, ligand-based reactivity in the presence of a spectator metal centre will be examined. Small molecules of particular interest in this review will include but not be limited to H2, O2, CO2, alcohols, silanes, and alkenes/alkynes.

This paper describes the regioselective electrophilic substitution of different ring positions in pyrimidine, pyrazine, and thienopyrimidine derivatives.

The frustrated Lewis pair (FLP) catalyzed hydrogenation of organic molecules is discussed. The saturation of polarized double bonds by FLP can be described as the nucleophilic addition of hydrides to the polar double bond prior to proton transfer. In contrast, the hydrogenation of olefins proceeds first by protonation forming a transient carbocation, which is subsequently attacked by the hydride. Both processes give rise for efficient conversion of unsaturated organic compounds by a metal-free methodology employing molecular hydrogen.

Treatment of pyridines, quinoline and methylthiopyrazine with the frustrated Lewis pair TMPMgCl·BF3 leads to organofluoroborates which react readily with a variety of aromatic aldehydes or activated ketones (II) to the corresponding carbinols (III) in the absence of a transition metal catalyst.

In the title catalysts, the substrate, typically a ketone, imine or N-heterocycle, remains in the outer sphere (OS). The catalyst transfers hydride and a proton to the unbound substrate either by a concerted or by a stepwise path. These include catalysts not always considered together, such as Bullock's ionic hydrogenation catalysts, bifunctional catalysts in the tradition of Shvo and Noyori and Stephan's frustrated Lewis pair catalysts. By omitting the oxidative addition, insertion and reductive elimination pathways of conventional inner sphere (IS) catalysts, these OS pathways are in principle equally open to inexpensive metals and even nonmetal catalysts. These OS pathways lead to useful selectivity properties, particularly Noyori's asymmetric catalysis, but much more remains to be done in this rapidly developing field.