Peter Kiraly

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

Simultaneously Enhancing Spectral Resolution and Sensitivity in Heteronuclear Correlation NMR Spectroscopy

BIRDs eye view: Adding periodic BIRD J-refocusing (BIRD=bilinear rotation decoupling) to data acquisition in an HSQC experiment causes broadband homonuclear decoupling, giving a single signal for each proton chemical shift. This pure shift method improves both resolution and signal-to-noise ratio, without the need for special data processing.

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.

Diastereomeric ratio determination by high sensitivity band-selective pure shift NMR spectroscopy

An NMR method is reported that allows diastereomeric ratios to be determined even in crowded spectra or where chemical shift differences are small compared to multiplet widths. Band-selective pure shift NMR collapses multiplets to singlets, greatly improving spectral resolution while largely retaining, or even enhancing, signal-to-noise ratio.

Active conformation in amine-thiourea bifunctional organocatalysis preformed by catalyst aggregation.

Self-activation: Takemotos catalyst gains access to its active conformation by equilibrating between its hydrogen-bonded intra- and intermolecular interactions in apolar aprotic solvents. By destabilization of the inactive monomeric conformations, the extended anti-anti thiourea conformation is preformed in the assembly. On leaving the assembly, this transient conformation has a structural preference to become a catalytically active monomeric species that has the potency for dual activation (see scheme).

Solvent-assisted spontaneous resolution of a 16-membered ring containing gold(I) showing short Au...Au aurophilic interaction and a figure-eight conformation.

The achiral 4,6-bis(diphenylphosphino) phenoxazine (nixantphos) ligand was used to synthesize a gold(I) complex, [Au2(nixantphos)2](NO3)2, containing a 16-membered [Au2(nixantphos)2](+2) cationic ring in a chiral figure-eight conformation. The single crystal X-ray diffraction analysis of [Au2(nixantphos)2](NO3)2.3MeOH.H2O (1) and [Au2(nixantphos)2](NO3)2.4MeCN (2) revealed a solvent-assisted spontaneous resolution of the [Au2(nixantphos)2](NO3)2 complex. By changing the nature of the solvent, homochiral hydrogen bonded helices (1) and heterochiral hydrogen bonded monomers (2) were obtained. Multinuclear NMR spectroscopy showed the evidence of chemical exchange phenomenon related to the interconversion of the enantiomeric skeletons of the 16-membered macrocycle in solution. The existence of the Au...Au aurophilic interaction was confirmed by the analysis of the spin-system in the (31)P NMR spectrum.

Internal motions and exchange processes in human ileal bile acid binding protein as studied by backbone 15N nuclear magnetic resonance spectroscopy

Human ileal bile acid binding protein (I-BABP), a member of the family of intracellular lipid binding proteins, is thought to play a role in the enterohepatic circulation of bile salts. Previously, we have shown by stopped-flow fluorescence analysis that positive binding cooperativity exhibited by I-BABP in its interactions with glycocholate (GCA) and glycochenodeoxycholate (GCDA), the two primary bile salts in humans, is related to a slow conformational change in the protein. In this study, we used backbone (15)N relaxation nuclear magnetic resonance (NMR) techniques to obtain residue-specific information about the internal dynamics of apo I-BABP and the doubly ligated I-BABP:GCA:GCDA complex on various time scales. According to our NMR data, bile salt binding is accompanied by a slight rigidification of the (15)N-(1)H bond vectors on the picosecond to nanosecond time scale, with most pronounced changes occurring in the C-D region. In contrast to the minor effects of ligation on fast motions, relaxation dispersion NMR experiments indicate a marked difference between the two protein states on the microsecond to millisecond time scale. In the apo form, an extensive network of conformational fluctuations is detected throughout segments of the EFGHIJ β-strands and the C-D loop, which cease upon complexation. Our NMR data are in agreement with a conformational selection model we proposed earlier for I-BABP and support the hypothesis of an allosteric mechanism of ligand binding. According to the NMR measurements, the helical cap region may have a less crucial role in mediating ligand entry and release than what has been indicated for fatty acid binding proteins.

Real-time pure shift 15N HSQC of proteins: a real improvement in resolution and sensitivity

Spectral resolution in proton NMR spectroscopy is reduced by the splitting of resonances into multiplets due to the effect of homonuclear scalar couplings. Although these effects are often hidden in protein NMR spectroscopy by low digital resolution and routine apodization, behind the scenes homonuclear scalar couplings increase spectral overcrowding. The possibilities for biomolecular NMR offered by new pure shift NMR methods are illustrated here. Both resolution and sensitivity are improved, without any increase in experiment time. In these experiments, free induction decays are collected in short bursts of data acquisition, with durations short on the timescale of J-evolution, interspersed with suitable refocusing elements. The net effect is real-time (t2) broadband homodecoupling, suppressing the multiplet structure caused by proton–proton interactions. The key feature of the refocusing elements is that they discriminate between the resonances of active (observed) and passive (coupling partner) spins. This can be achieved either by using band-selective refocusing or by the BIRD element, in both cases accompanied by a nonselective 180° proton pulse. The latter method selects the active spins based on their one-bond heteronuclear J-coupling to 15N, while the former selects a region of the 1H spectrum. Several novel pure shift experiments are presented, and the improvements in resolution and sensitivity they provide are evaluated for representative samples: the N-terminal domain of PGK; ubiquitin; and two mutants of the small antifungal protein PAF. These new experiments, delivering improved sensitivity and resolution, have the potential to replace the current standard HSQC experiments.

Self-assembly of gold(I) with diphosphine and bitopic nitrogen donor linkers in the presence of trifluoroacetate anion: formation of coordination polymer versus discrete macrocycle

The rigid Au2(dppbz)(CF3COO)2 (1) precursor (dppbz = 1,2-bis(diphenylphosphino)benzene) with preorganised syn-gold(I) centers has been self-assembled with 4,4′-bipyridyl (bipy) and 1,2-trans-bis(4-pyridyl)-ethylene (bipyen) to afford different supramolecular architectures: a unique [Au2(dppbz)(bipy)]n(CF3COO)2n (2) coordination polymer and a discrete [Au4(dppbz)2(bipyen)2](CF3COO)4 (3) macrocycle in response to changes in bitopic nitrogen donor linker.

Controlling the Composition of Nanosize Hexagonal WO3 for Gas Sensing

Hexagonal (h-) WO3 was prepared through heating hexagonal ammonium tungsten bronze (HATB), (NH4)0.07(NH3)0.04(H2O)0.09WO2.95. By adjusting the heating temperature and atmosphere of HATB, we could control the oxidation state of tungsten atoms and the residual NH3/NH4 + content in h-WO3. The as-produced h-WO3 nanoparticles with different composition were tested as gas sensors and the effect of composition on gas sensing properties was studied. Our results showed that oxidized h-WO3 had the best sensitivity to H2S.