Quo Vadis CO2 Activation: Catalytic Reduction of CO2 to Methanol Using Aluminum and Gallium/Carbon-based Ambiphiles.

We report on so-called "hidden FLPs" (FLP: frustrated Lewis pair) consisting of a phosphorus ylide featuring a group 13 fragment in the ortho position of a phenyl ring scaffold to form five-membered ring structures. Although the formation of the Lewis acid/base adducts was observed in the solid state, most of the title compounds readily react with carbon dioxide to provide stable insertion products. Strikingly, 0.3-3.0 mol% of the reported aluminum and gallium/carbon-based ambiphiles catalyze the reduction of CO2 to methanol with satisfactory high selectivity and yields using pinacol borane as stoichiometric reduction equivalent. Comprehensive computational studies provided valuable mechanistic insights and shed more light on activity differences.

A crystalline aluminium-carbon-based ambiphile capable of activation and catalytic transfer of ammonia in non-aqueous media.

Despite recent achievements in the field of frustrated Lewis pairs (FLPs) for small molecule activations, the reversible activation and catalytic transformations of N-H-activated ammonia remain a challenge. Here we report on a rare combination of an aluminium Lewis acid and a carbon Lewis base. A so-called hidden FLP consisting of a phosphorus ylide featuring an aluminium fragment in the ortho position of a phenyl ring scaffold is introduced. Although the formation of the Lewis acid/base adduct is observed in the solid state, which at first glance leads to formally quenched FLP reactivity, we show that the title compound readily reacts with non-aqueous ammonia thermoneutrally and splits the N-H bond reversibly at ambient temperature. In addition, NH3 transfer reactions mediated by a main-group catalyst are presented. This proof-of-principle study is expected to initiate further activities in utilizing N-H-activated ammonia as a readily available, atom-economical nitrogen source.

Dispersion Energy-Stabilized Boron and Phosphorus Lewis Pairs.

An isostructural series of boron/phosphorus Lewis pairs was systematically investigated. The association constants of the Lewis pairs were determined at variable temperatures, enabling the extraction of thermodynamic parameters. The stabilization of the Lewis adduct increased with increasing size of the dispersion energy donor groups, although the donor and acceptor properties of the Lewis pairs remained largely unchanged. This data was utilized to challenge state-of-the-art quantum chemical methods, which finally led to an enhanced workflow for the determination of thermochemical properties of weakly bound Lewis pairs within an accuracy of 0.6 to 1.0 kcal mol-1 for computed association free energies.

Structure-Reactivity Relationships in Borane-Based FLP-Catalyzed Hydrogenations, Dehydrogenations, and Cycloisomerizations.

ConspectusThe activation of molecular hydrogen by main-group element catalysts is an extremely important approach to metal-free hydrogenations. These so-called frustrated Lewis pairs advanced within a short period of time to become an alternative to transition metal catalysis. However, deep understanding of the structure-reactivity relationship is far less developed compared to that of transition metal complexes, although it is paramount for advancing frustrated Lewis pair chemistry.In this Account, we provide detailed insight into how Lewis acidity and Lewis basicity correlate to reactivity. The reactivity of frustrated Lewis pairs will be systematically discussed in context with selected reactions. The influence of major electronic modifications of the Lewis pairs is correlated with the ability to activate molecular hydrogen, to channel reaction kinetics and reaction pathways, or to achieve C(sp3)-H activations.First, we will describe how we entered this emerging field of research after quickly realizing that information was lacking on how the reactivity changes with modification of the frustrated Lewis pair. This led us to the development of a qualitative and quantitative structure-reactivity relationship in metal-free imine hydrogenations. The imine hydrogenation was utilized as the model reaction to experimentally determine the activation parameters of the FLP-mediated hydrogen activation for the first time. This kinetic study revealed autoinduced catalytic profiles when Lewis acids weaker than tris(pentafluorophenyl)borane were applied, opening up to study the Lewis base dependency within one system. With this knowledge of the interplay between Lewis acid strength and Lewis basicity, we developed methods for the hydrogenation of densely functionalized nitroolefins, acrylates, and malonates. Here, the reduced Lewis acidity needed to be counterbalanced by a suitable Lewis base to ensure efficient hydrogen activation. The opposite measure was necessary for the hydrogenation of unactivated olefins. For these, comparably less electron-releasing phosphanes were required to generate strong Brønsted acids by hydrogen activation. These systems displayed highly reversible hydrogen activation even at temperatures as low as -60 °C. A systematic study of these systems enabled the development of acceptorless dehydrocouplings of amines with silanes and dehydrogenations of aza-heterocycles by C(sp3)-H activations. Furthermore, the C(sp3)-H and π-activation was utilized to achieve cycloisomerizations by carbon-carbon and carbon-nitrogen bond formations. Lastly, new frustrated Lewis pair systems featuring weak Lewis bases as active components in the hydrogen activation were developed for the reductive deoxygenation of phosphane oxides and carboxylic acid amides.

Boron-Centered Lewis Superacid through Redox-Active Ligands: Application in C-F and S-F Bond Activation.

A series of redox-responsive ferrocenyl-substituted boranes and boronic esters were synthesized. Oxidation of the ferrocenyl ligand to the ferrocenium resulted in a drastic increase in the Lewis acidity beyond the strength of SbF5 , which was investigated experimentally and computationally. The resulting highly Lewis acidic boron compounds were used for catalytic C-F and S-F bond activation.

Imidazolyl-Substituted Benzo- and Naphthodithiophenes as Precursors for the Synthesis of Transient Open-Shell Quinoids.

The synthesis of three novel imidazolyl-substituted sulfur-containing heteroacenes is reported. These heteroacenes consisting of annelated benzo- and naphthothiophenes serve as precursors for the generation of open-shell quinoid heteroacenes by oxidation with alkaline ferric cyanide. Spectroscopic and computational experiments support the formation of reactive open-shell quinoids, which, however, quickly produce paramagnetic polymeric material.

Sigmatropic [1,5] Carbon Shift of Transient C3 Ammonium Enolates.

The stereospecific sigmatropic [1,5] carbon shift of C3 ammonium enolates is discovered. According to mechanistic, kinetic and computational experiments, this new rearrangement proceeds via the catalytic generation of a transient C3 ammonium enolate by intramolecular aza-Michael addition. This intermediate rapidly undergoes [1,5] sigmatropic carbon migration to furnish the respective tetrahydroquinoline-4-ones with excellent diastereoselectivities of d.r. >99 : 1 and in 61-98 % yield.

Impact of Heterocycle Annulation on NIR Absorbance in Quinoid Thioacene Derivatives.

The synthesis and characterisation of a homologous series of quinoid sulfur-containing imidazolyl-substituted heteroacenes is described. The optoelectronic and magnetic properties were investigated by UV/vis, fluorescence and EPR spectroscopy as well as quantum-chemical calculations, and were compared to those of the corresponding benzo congener. The room-temperature and atmospherically stable quinoids display strong absorption in the NIR region between 678 and 819 nm. The dithieno[3,2-b:2',3'-d]thiophene and the thieno[2',3':4,5]thieno[3,2-b]thieno[2,3-d]thiophene derivatives were EPR active at room temperature. For the latter, variable-temperature EPR spectroscopy revealed the presence of a thermally accessible triplet state, with a singlet-triplet separation of 14.1 kJ mol-1 .

Coupling of CO2 and epoxides catalysed by novel N-fused mesoionic carbene complexes of nickel(II).

We report the syntheses of two rigid mesoionic carbene (MIC) ligands with a carbazole backbone via an intramolecular Finkelstein-cyclisation cascade and investigate their coordination behavior towards nickel(II) acetate. Despite the nickel(II) carbene complexes 4a,b showing only minor differences in their chemical composition, they display curious differences in their chemical properties, e.g. solubility. Furthermore, the potential of these novel MIC complexes in the coupling of carbon dioxide and epoxides as well as the differences in reactivity compared to classical NHC-derived complexes are evaluated.

Diastereoselective Synthesis of Dihydro-quinolin-4-ones by a Borane-Catalyzed Redox-Neutral endo-1,7-Hydride Shift.

The borane-catalyzed synthesis of dihydroquinoline-4-ones is developed. The amino-substituted chalcones undergo a 1,7-hydride shift upon Lewis acid activation to form a zwitterionic iminium enolate, which collapses to the dihydroquinoline-4-one scaffold. The reaction proceeds in high yields (75-99%) with an excellent diastereoselectivity of up to >99:1 (cis:trans). The reaction mechanism is investigated by kinetic, isotope labeling, and computational experiments.

Mixed-Valence Compounds as Polarizing Agents for Overhauser Dynamic Nuclear Polarization in Solids*.

Herein, we investigate a novel set of polarizing agents-mixed-valence compounds-by theoretical and experimental methods and demonstrate their performance in high-field dynamic nuclear polarization (DNP) NMR experiments in the solid state. Mixed-valence compounds constitute a group of molecules in which molecular mobility persists even in solids. Consequently, such polarizing agents can be used to perform Overhauser-DNP experiments in the solid state, with favorable conditions for dynamic nuclear polarization formation at ultra-high magnetic fields.

Hydrogenation of Secondary Amides using Phosphane Oxide and Frustrated Lewis Pair Catalysis.

The metal-free catalytic hydrogenation of secondary carboxylic acid amides is developed. The reduction is realized by two new catalytic reactions. First, the amide is converted into the imidoyl chloride by triphosgene (CO(OCCl3 )2 ) using novel phosphorus(V) catalysts. Second, the in situ generated imidoyl chlorides are hydrogenated in high yields by an FLP-catalyst. Mechanistic and quantum mechanical calculations support an autoinduced catalytic cycle for the hydrogenation with chloride acting as unusual Lewis base for FLP-mediated H2 -activation.

FLP-catalysis meets hydrogen-bond activation.

The potential of two chiral amidines and three non-chiral boranes in the metal-free hydrogen activation was explored. The resulting chiral amidiunium borohydride salts were investigated in asymmetric hydrogenation reactions of ketimines, activated double bonds and dehydro amioacid esters.

Dually Crosslinked Supramolecular Hydrogel for Cancer Biomarker Sensing.

Lysophosphatidic acid (LPA) as the biomarker of early stage ovarian cancer is essentially difficult to detect due to lack of target spots. A dually crosslinked supramolecular hydrogel (DCSH) was developed to achieve sensing of LPA, which acts as a competitive guest molecule triggering the responsive crosslinking of the DCSH. Through this strategy, the surface plasmon resonance combined with optical waveguide spectroscopy could be used to quantitatively detect LPA with a responsive range covering physiological conditions (in pure form as well as mimicking LPA plasma solution) with high selectivity and sensitivity. LPA efficiently immerses into the host molecule ß-cyclodextrin (ß-CD) up to a 1:2 ratio by the competitive interaction mechanism, confirmed by one-dimensional nuclear overhauser effect spectroscopy (1D NOESY), high-resolution mass spectrometry (HRMS), isothermal titration calorimetry (ITC), and computational simulation. Our method opens a new strategy to detect biomarkers without target spots and provides a platform for surface plasmon resonance (SPR)-based sensors measuring small molecules.

Palladium-Catalyzed Polycondensation for the Synthesis of Poly(Aryl)Sulfides.

The palladium-catalyzed CS cross coupling reaction is investigated as a novel efficient tool for the synthesis of poly(phenyl)sulfide derivatives. The reaction proceeds through the polycondensation of dibromo arenes with a H2 S-surrogate to yield poly(aryl)sulfides. The reaction is generalized by the synthesis of so-far-unprecedented poly(2,5-thiophene)sulfide. Number average molecular weights (Msss ) of up to 3780 and 1770 g mol-1 for poly(phenyl)sulfide and poly(thiophene)sulfide are achieved with degrees of polymerization (DPn ) of 10 and 7, respectively. A mechanism for the new polycondensation reaction is suggested.

Redox-responsive phosphonite gold complexes in hydroamination catalysis.

Very high activities were observed in the redox-induced hydroamination of alkynes by employing a redox-active gold(i) complex featuring an electron-deficient, terphenyl-substituted phosphonite-based ligand. The hydroamination proceeds roughly two-fold faster with the in situ oxidized catalysts than with their reduced form.

Frustrated Lewis Pair Catalyzed Hydrogenation of Amides: Halides as Active Lewis Base in the Metal-Free Hydrogen Activation.

A method for the metal-free reduction of carboxylic amides using oxalyl chloride as an activating agent and hydrogen as the final reductant is introduced. The reaction proceeds via the hydrogen splitting by B(2,6-F2-C6H3)3 in combination with chloride as the Lewis base. Density functional theory calculations support the unprecedented role of halides as active Lewis base components in the frustrated Lewis pair mediated hydrogen activation. The reaction displays broad substrate scope for tertiary benzoic acid amides and α-branched carboxamides.

Electrophilic Phosphonium Cation-Mediated Phosphane Oxide Reduction Using Oxalyl Chloride and Hydrogen.

The metal-free reduction of phosphane oxides with molecular hydrogen (H2 ) using oxalyl chloride as activating agent was achieved. Quantum-mechanical investigations support the heterolytic splitting of H2 by the in situ formed electrophilic phosphonium cation (EPC) and phosphane oxide and subsequent barrierless conversion to the phosphane and HCl. The reaction can also be catalyzed by the frustrated Lewis pair (FLP) consisting of B(2,6-F2 C6 H3 )3 and 2,6-lutidine or phosphane oxide as Lewis base. This novel reduction was demonstrated for triaryl and diaryl phosphane oxides providing access to phosphanes in good to excellent yields (51-93 %).

Borane-Catalyzed Synthesis of Quinolines Bearing Tetrasubstituted Stereocenters by Hydride Abstraction-Induced Electrocyclization.

The borane-catalyzed synthesis of quinoline derivatives bearing tetrasubstituted stereocenters from vinyl anilines has been developed. Mechanistic studies and quantum-mechanical investigations support the hydride abstraction/electrocyclization/hydride addition mechanism. The products were obtained in up to 99 % yield with a diastereoselectivity of >99 % in favour for the 3a-5-cis isomer.

Double-Strand DNA Breaks Induced by Paracyclophane Gold(I) Complexes.

Gold(I) complexes of ClickPhos [2.2]paracyclophane ligands were synthesized in excellent yields and fully characterized by spectroscopic methods as well as X-ray crystallography. The complexes exhibit a rigid ligand backbone and a triazolyl moiety and were systematically studied with respect to their cytotoxic properties. In combination with the ionic complex [(GemPhos)Au(tht)][ClO4 ] (tht=tetrahydrothiophene), in which the gold(I) atom exhibits a distorted trigonal coordination sphere of two phosphines and a labile tht ligand, their efficiency in cytotoxicity was investigated in HeLa, MCF7, and HCT116 cells as well as in a zebrafish model. Their cytotoxicity and their mechanisms of action are different and involve apoptosis, necrosis, and DNA damage. The compounds presented herein are potent metal-based cytostatics displaying LD50 values from 3.5-38 µm in different tumor cell lines and induce double-strand DNA breaks (DSB) as shown by H2AX phosphorylation (γH2AX) at foci of DSBs.