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 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.

In this paper, we report on the development of a bench-stable borane for frustrated Lewis pair catalyzed reduction of aldehydes, ketones and enones. The deliberate for finetuning of structural and electronic parameters of Lewis acid component and the choice of Lewis base provided for the first time, a moisture tolerant FLP catalyst. Related NMR and DFT studies underpinned the unique behavior of this FLP catalyst and gave insight into the catalytic activity of the resulting FLP catalyst.

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.

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.[1] 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. [2,3] 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. [2] Using steric hindrance as a critical design element, several combinations of bulky Lewis acid-base pairs were effectively probed for heterolytic cleavage of hydrogen. [4][5][6] Moreover, this remarkable capacity of FLPs was exploited in metal-free hydrogenation procedures.[7] Additionally, the bifunctional and unquenched nature of the FLPs makes them capable of reacting with alkenes, [8] dienes, [9] acetylenes, [10] and THF.[5f]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 [11] (1) as the LA component.[12] Because of the hard-type Lewis acidity of boron in 1 and its inactivation by common oxygen-and/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 congestion around the boron center in FLP I and its parallel decrease around the LB could lead to a Lewis pair (FLP II) that may have a markedly higher tolerance for the functionalities of common organic molecules. Thus, the steric demands imposed on the boron center by additional orthoaryl substituents are such that they can prevent or markedly decrease the complexation ability with normal Lewis bases but still allow the cleavage of the small hydrogen molecule. Additionally, we assumed that the increased shielding around boron in FLP II could preclude its addition to olefins, therefore creating a unique opportunity to investigate the chemoselectivity of FLP-catalyzed hydroge...

This study advances strategy and design in catalysts and reagents for fluorous and supercritical CO(2) chemistry by defining the structural requirements for insulating a typical active site from a perfluoroalkyl segment. The vertical ionization potentials of the phosphines P((CH(2))(m)R(f8))(3) (m = 2 (2) to 5 (5)) are measured by photoelectron spectroscopy, and the enthalpies of protonation by calorimetry (CF(3)SO(3)H, CF(3)C(6)H(5)). They undergo progressively more facile (energetically) ionization and protonation (P(CH(2)CH(3))(3) > 5 > 4 approximately equal to P(CH(3))(3) > 3 > 2), as expected from inductive effects. Equilibrations of trans-Rh(CO)(Cl)(L)(2) complexes (L = 2, 3) establish analogous Lewis basicities. Density functional theory is used to calculate the structures, energies, ionization potentials, and gas-phase proton affinities (PA) of the model phosphines P((CH(2))(m)()CF(3))(3) (2'-9'). The ionization potentials of 2'-5' are in good agreement with those of 2-5, and together with PA values and analyses of homodesmotic relationships are used to address the title question. Between 8 and 10 methylene groups are needed to effectively insulate a perfluoroalkyl segment from a phosphorus lone pair, depending upon the criterion employed. Computations also show that the first carbon of a perfluoroalkyl segment exhibits a much greater inductive effect than the second, and that ionization potentials of nonfluorinated phosphines P((CH(2))(m)CH(3))(3) reach a limit at approximately nine carbons (m = 8).

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.