Just before splitting: A mechanistic model has been proposed for H2 activation by sterically demanding phosphine–borane Lewis pairs. There is theoretical evidence for noncovalent intermolecular association of donor–acceptor molecules to form a flexible but energetically strained complex, which provides preorganized active centers for heterolytic HH bond cleavage (see picture).

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.

The mechanism of enantioselective Michael addition of acetylacetone to a nitroolefin catalyzed by a thiourea-based chiral bifunctional organocatalyst is investigated using density functional theory calculations. A systematic conformational analysis is presented for the catalyst, and it is shown that both substrates coordinate preferentially via bidentate hydrogen bonds. The deprotonation of the enol form of acetylacetone by the amine of the catalyst is found to occur easily, leading to an ion pair characterized by multiple H-bonds involving the thiourea unit as well. Two distinct reaction pathways are explored toward the formation of the Michael product that differ in the mode of electrophile activation. Both reaction channels are shown to be consistent with the notion of noncovalent organocatalysis in that the transition states leading to the Michael adduct are stabilized by extensive H-bonded networks. The comparison of the obtained energetics for the two pathways allows us to propose an alternative mechanistic rationale for asymmetric C-C bond forming reactions catalyzed by bifunctional thiourea derivatives. The origin of enantioselectivity in the investigated reaction is also discussed.

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.

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.

ABSTRACT:A detailed molecular orbital treatment of the heterolytic hydrogen splitting by bulky Lewis acid-base pairs is presented. The frontier molecular orbitals of the proposed reactive intermediate are shown to be preorganized but otherwise practically identical to those of the free acid and base molecules. The concerted interaction of the Lewis centers with hydrogen leading to the polarization and, ultimately, to the cleavage of the HOH bond is examined, and the bridge role of hydrogen molecule in the electron transfer is pointed out. The formation of the new covalent bonds is monitored by bond order and natural localized molecular orbital calculations, and found to be synchronous. The stability of the product is interpreted on the basis of favorable orbital interactions. A comparison of various hydrogen activation mechanisms emphasizes the common donation/back-donation motifs and the different ways of making them feasible.

Bevorstehende Scheidung: Ein theoretisches Modell für den Mechanismus der H2‐Aktivierung durch Lewis‐Paare aus sperrigen Phosphanen und Boranen liefert Hinweise auf eine nichtkovalente Anlagerung der Donor‐ und Akzeptormoleküle unter Bildung eines flexiblen, aber gespannten Komplexes mit präorganisierten aktiven Zentren für die heterolytische Spaltung der H‐H‐Bindung (siehe Bild).

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.