Imre Pápai

Rationalizing the Reactivity of Frustrated Lewis Pairs: Thermodynamics of H2 Activation and the Role of Acid−Base Properties

The acid-base strengths of recently reported frustrated Lewis pairs and their relation with the thermodynamic feasibility of heterolytic hydrogen splitting reactions are analyzed in terms of quantum chemical calculations. Reaction free energies of hydrogenation processes are computed, and an energy partitioning scheme is introduced, which involves quantitative measures of the acidity and basicity of the reacting Lewis centers. Additional terms are also included that account for possible dative bond formation between the active sites and for stabilizing electrostatic interactions occurring in the product species. For intermolecular combinations of donor-acceptor components, the calculated reaction free energies are found to correlate well with the cumulative acid-base strengths. Product stabilization for these systems represents a notable contribution to the overall energetics; however, it generally shows only a slight variation for the investigated series. The reactivity of linked donor-acceptor pairs is primarily governed by acid-base properties as well, but the magnitude of stabilizing effects arising from acid-base cooperativity of active sites is also of significant importance in determining the thermodynamic feasibility of the reactions.

Expanding the scope of metal-free catalytic hydrogenation through frustrated Lewis pair design

The further development of the field of catalysis is based on the discovery, understanding, and implementation of novel activation modes that allow unprecedented transformations and open new perspectives in synthetic chemistry. In this context, the recently introduced concept of frustrated Lewis pair (FLP) from the Stephan research group represents a fundamental and novel strategy to develop catalysts based on main-group elements for small-molecule activation. These sterically encumbered Lewis acid–base systems are not able to form a stable donor–acceptor adduct, nevertheless, an intermolecular association of the Lewis acidic (LA) and basic (LB) components to a unique “frustrated complex” was proposed. Our research group has also shown that this encounter pair cleaves hydrogen in a cooperative manner and the steric congestion implies a strain, which can be directly utilized for bond activation. Using steric hindrance as a critical design element, several combinations of bulky Lewis acid–base pairs were effectively probed for heterolytic cleavage of hydrogen. Moreover, this remarkable capacity of FLPs was exploited in metal-free hydrogenation procedures. Additionally, the bifunctional and unquenched nature of the FLPs makes them capable of reacting with alkenes, dienes, acetylenes, and THF. Although this type of reactivity represents a breakthrough in main-group chemistry, its enhanced and non-orthogonal nature obviously limits the synthetic applicability of FLPs. Herein we report an attempt to develop frustrated Lewis pairs with orthogonal reactivity and improved functional-group tolerance for catalytic metal-free hydrogenation. The previously reported FLP-based hydrogen activation relied mostly on tris(pentafluorophenyl)borane (1) as the LA component. Because of the hard-type Lewis acidity of boron in 1 and its inactivation by common oxygenand/or nitrogen-containing molecules, careful substrate design was needed for successful catalytic hydrogenation reactions. This synthetic limitation triggered us to develop FLP catalysts that have a broader range of applications and possible selectivity in reduction processes. Our design concept for increased functional-group tolerance is based on the simple hypothesis that steric hindrance in FLPs is a relative phenomenon (Figure 1): further increase of

A frustrated-Lewis-pair approach to catalytic reduction of alkynes to cis-alkenes

Frustrated Lewis pairs are compounds containing both Lewis acidic and Lewis basic moieties, where the formation of an adduct is prevented by steric hindrance. They are therefore highly reactive, and have been shown to be capable of heterolysis of molecular hydrogen, a property that has led to their use in hydrogenation reactions of polarized multiple bonds. Here, we describe a general approach to the hydrogenation of alkynes to cis-alkenes under mild conditions using the unique ansa-aminohydroborane as a catalyst. Our approach combines several reactions as the elementary steps of the catalytic cycle: hydroboration (substrate binding), heterolytic hydrogen splitting (typical frustrated-Lewis-pair reactivity) and facile intramolecular protodeborylation (product release). The mechanism is verified by experimental and computational studies. Frustrated Lewis pairs have been shown to be capable of heterolysis of strong covalent bonds such as those in molecular hydrogen, and have been used in the hydrogenation of polar multiple bonds. Here, a new type of ansa-aminohydroborane is shown to be active for the partial hydrogenation of alkynes under mild conditions.

On the Mechanism of B(C6F5)3-Catalyzed Direct Hydrogenation of Imines: Inherent and Thermally Induced Frustration

The reaction mechanism for the transition metal free direct hydrogenation of bulky imines catalyzed by the Lewis acid B(C6F5)3 is investigated in detail by quantum chemical calculations. A recently introduced mechanistic model of heterolytic hydrogen splitting that is based on noncovalent association of bulky Lewis acid-base pairs is shown to account for the reactivity of imine-borane as well as amine-borane systems. Possible catalytic cycles are examined, and the results provide solid support for the imine reduction pathway proposed from experimental observations. In addition, the feasibility of an autocatalytic route initiated by amine-borane hydrogen cleavage is demonstrated. Conceptual issues regarding the notion of frustration are also discussed. The observed reactivity is interpreted in terms of thermally induced frustration, which refers to thermal activation of strained dative adducts of bulky Lewis donor-acceptor pairs to populate their reactive frustrated complex forms.

Density functional study of nitrogen oxides

Equilibrium geometries, bond dissociation energies, dipole moments, harmonic vibrational frequencies, and infrared intensities were calculated for a set of ten neutral nitrogen oxides (NO, NO2, NO3, N2O, sym N2O2, asym N2O3, sym N2O3, sym N2O4, asym N2O4, and N2O5) by applying one local and two gradient‐corrected nonlocal functionals in a Gaussian‐type‐orbital density functional method. Comparison with available experimental data shows that, except for the bond dissociation energies, the local functional gives very accurate molecular properties. Nonlocal functionals considerably improve the bond dissociation energies, but the results still overestimate the experimental values by about 10 kcal/mol on average. For the other properties, the results obtained with nonlocal functionals are not necessarily superior to those calculated with the local functional. The properties of two molecules (sym N2O3 and asym N2O4) are predicted for the first time and several reassignments are proposed in the vibrational spect...

Reactivity Models of Hydrogen Activation by Frustrated Lewis Pairs: Synergistic Electron Transfers or Polarization by Electric Field?

Two alternative qualitative reactivity models have recently been proposed to interpret the facile heterolytic cleavage of H2 by frustrated Lewis pairs (FLPs). Both models assume that the reaction takes place via reactive intermediates with preorganized acid/base partners; however, they differ in the mode of action of the active centers. In the electron transfer (ET) model, the hydrogen activation is associated with synergistic electron donation processes with the simultaneous involvement of active centers and the bridging hydrogen, showing similarity to transition-metal-based and other H2-activating systems. In contrast, the electric field (EF) model suggests that the heterolytic bond cleavage occurs as a result of polarization by the strong EF present in the cavity of the reactive intermediates. To assess the applicability of the two conceptually different mechanistic views, we examined the structural and electronic rearrangements as well as the EFs along the H2 splitting pathways for a representative set of reactions. The analysis reveals that electron donations developing already in the initial phase are general characteristics of all studied reactions, and the related ET model provides qualitative interpretation for the main features of the reaction pathways. On the other hand, several arguments have emerged that cast doubt on the relevance of EF effects as a conceptual basis in FLP-mediated hydrogen activation.

Catalytic Hydrogenation with Frustrated Lewis Pairs: Selectivity Achieved by Size‐Exclusion Design of Lewis Acids

Catalytic hydrogenation that utilizes frustrated Lewis pair (FLP) catalysts is a subject of growing interest because such catalysts offer a unique opportunity for the development of transition-metal-free hydrogenations. The aim of our recent efforts is to further increase the functional-group tolerance and chemoselectivity of FLP catalysts by means of size-exclusion catalyst design. Given that hydrogen molecule is the smallest molecule, our modified Lewis acids feature a highly shielded boron center that still allows the cleavage of the hydrogen but avoids undesirable FLP reactivity by simple physical constraint. As a result, greater latitude in substrate scope can be achieved, as exemplified by the chemoselective reduction of α,β-unsaturated imines, ketones, and quinolines. In addition to synthetic aspects, detailed NMR spectroscopic, DFT, and (2)H isotopic labeling studies were performed to gain further mechanistic insight into FLP hydrogenation.

Concerted attack of frustrated Lewis acid–base pairs on olefinic double bonds: a theoretical study

A computational approach reveals cooperative action of the preorganized acidic and basic centers of the frustrated P(t-Bu)(3)/B(C(6)F(5))(3) Lewis pair on olefinic bonds as the key to the observed regioselective addition reaction.

On the Mechanism of Bifunctional Squaramide-Catalyzed Organocatalytic Michael Addition: A Protonated Catalyst as an Oxyanion Hole

A joint experimental-theoretical study of a bifunctional squaramide-amine-catalyzed Michael addition reaction between 1,3-dioxo nucleophiles and nitrostyrene has been undertaken to gain insight into the nature of bifunctional organocatalytic activation. For this highly stereoselective reaction, three previously proposed mechanistic scenarios for the critical CC bond-formation step were examined. Accordingly, the formation of the major stereoisomeric products is most plausible by one of the bifunctional pathways that involve electrophile activation by the protonated amine group of the catalyst. However, some of the minor product isomers are also accessible through alternative reaction routes. Structural analysis of transition states points to the structural invariance of certain fragments of the transition state, such as the protonated catalyst and the anionic fragment of approaching reactants. Our topological analysis provides deeper insight and a more general understanding of bifunctional noncovalent organocatalysis.

Dihydrooxazine Oxides as Key Intermediates in Organocatalytic Michael Additions of Aldehydes to Nitroalkenes

Pause and play: dihydrooxazine oxides are stable intermediates that are protonated directly, without the intermediacy of the zwitterions, in organocatalytic Michael additions of aldehydes and nitroalkenes (see scheme, R=alkyl). Protonation of these species explains both the role of the acid co-catalyst in these reactions, and the observed stereochemistry when the reaction is conducted with α-alkylnitroalkenes.