Markovnikov-Selective Cobalt-Catalyzed Wacker-Type Oxidation of Styrenes into Ketones under Ambient Conditions Enabled by Hydrogen Bonding.

The replacement of palladium catalysts for Wacker-type oxidation of olefins into ketones by first-row transition metals is a relevant approach for searching more sustainable protocols. Besides highly sophisticated iron catalysts, all the other first-row transition metal complexes have only led to poor activities and selectivities. Herein, we show that the cobalt-tetraphenylporphyrin complex is a competent catalyst for the aerobic oxidation of styrenes into ketones with silanes as the hydrogen sources. Remarkably, under room temperature and air atmosphere, the reactions were exceedingly fast (up to 10 minutes) with a low catalyst loading (1 mol %) while keeping an excellent chemo- and Markovnikov-selectivity (up to 99 % of ketone). Unprecedently high TOF (864 h-1 ) and TON (5,800) were reached for the oxidation of aromatic olefins under these benign conditions. Mechanistic studies suggest a reaction mechanism similar to the Mukaiyama-type hydration of olefins with a change in the last fundamental step, which controls the chemoselectivity, thanks to a unique hydrogen bonding network between the ethanol solvent and the cobalt peroxo intermediate.

Iron-Catalyzed Intermolecular C-N Cross-Coupling Reactions via Radical Activation Mechanism.

A concept for intermolecular C-N cross-coupling amination has been discovered using tetrazoles and aromatic and aliphatic azides with boronic acids under iron-catalyzed conditions. The amination follows an unprecedented metalloradical activation mechanism that is different from traditional metal-catalyzed C-N cross-coupling reactions. The scope of the reaction has been demonstrated by the employment of a large number of tetrazoles, azides, and boronic acids. Moreover, several late-stage aminations and a short synthesis of a drug candidate have been showcased for further synthetic utility. Collectively, this iron-catalyzed C-N cross-coupling should have wide applications in the context of medicinal chemistry, drug discovery, and pharmaceutical industries.

Reactivity of a Unique Si(I)-Si(I)-Based η2-Bis(silylene) Iron Complex.

In this paper, we report the synthesis of a unique silicon(I)-based metalla-disilirane and report on its reactivity toward TMS-azide and benzophenone. Metal complexes containing disilylenes ((bis)silylenes with a Si-Si bond) are known, but direct ligation of the Si(I) centers to transition metals always generated dinuclear species. To overcome this problem, we targeted the formation of a mononuclear iron(0)-silicon(I)-based disilylene complex via templated synthesis, starting with ligation of two Si(II) centers to iron(II), followed by a two-step reduction. The DFT structure of the resulting η2-disilylene-iron complex reveals metal-to-silicon π-back donation and a delocalized three-center-two-electron (3c-2e) aromatic system. The Si(I)-Si(I) bond displays unusual but well-defined reactivity. With TMS-azide, both the initial azide adduct and the follow-up four-membered nitrene complex could be isolated. Reaction with benzophenone led to selective 1,4-addition into the Si-Si bond. This work reveals that selective reactions of Si(I)-Si(I) bonds are made possible by metal ligation.

Atypical and Asymmetric 1,3-P,N Ligands: Synthesis, Coordination and Catalytic Performance of Cycloiminophosphanes.

Novel seven-membered cyclic imine-based 1,3-P,N ligands were obtained by capturing a Beckmann nitrilium ion intermediate generated in situ from cyclohexanone with benzotriazole, and then displacing it by a secondary phosphane under triflic acid promotion. These "cycloiminophosphanes" possess flexible non-isomerizable tetrahydroazepine rings with a high basicity; this sets them apart from previously reported iminophophanes. The donor strength of the ligands was investigated by using their P-κ1 - and P,N-κ2 -tungsten(0) carbonyl complexes, by determining the IR frequency of the trans-CO ligands. Complexes with [RhCp*Cl2 ]2 demonstrated the hemilability of the ligands, giving a dynamic equilibrium of κ1 and κ2 species; treatment with AgOTf gives full conversion to the κ2 complex. The potential for catalysis was shown in the RuII -catalyzed, solvent-free hydration of benzonitrile and the RuII - and IrI -catalyzed transfer hydrogenation of cyclohexanone in isopropanol. Finally, to enable access to asymmetric catalysts, chiral cycloiminophosphanes were prepared from l-menthone, as well as their P,N-κ2 -RhIII and a P-κ1 -RuII complexes.

Effect-directed analysis and chemical identification of agonists of peroxisome proliferator-activated receptors in white button mushroom.

Obesity has a serious effect on human health. It relates to metabolic syndrome, including the associated disorders such as type 2 diabetes, heart disease, stroke and hyperemia. The peroxisome proliferator-activated receptors (PPARs) are important receptors to control fat metabolism in the human body. Because of the safety concerns of synthetic drugs targeting PPARs, ligands from natural sources have drawn interest. Earlier, we have found high PPAR activities in extracts from Agaricus bisporus (white button mushroom, WBM). WBM contains a wide range of candidate compounds which could be agonists of PPARs. To identify which compounds are responsible for PPAR activation by WBM extracts, we used fractionation coupled to effect-directed analysis with reporter gene assays specific for all three PPARs for purification and LC/MS-TOF and NMR for compound identification in purified active fractions. Surprisingly, we identified the relatively common dietary fatty acid, linoleic acid, as the main ligand of PPARs in WBM. Possibly, the relatively low levels of linoleic acid in WBM are sufficient and instrumental in inducing its anti-obesogenic effects, avoiding high energy intake and negative health effects associated with high levels of linoleic acid consumption. However, it could not be excluded that a minor relatively potent compound contributes towards PPAR activation, while the anti-obesity effects of WBM may be further enhanced by receptor expression modulating compounds or compounds with completely PPAR unrelated modes of action.

Photoinduced and Thermal Single-Electron Transfer to Generate Radicals from Frustrated Lewis Pairs.

Archetypal phosphine/borane frustrated Lewis pairs (FLPs) are famed for their ability to activate small molecules. The mechanism is generally believed to involve two-electron processes. However, the detection of radical intermediates indicates that single-electron transfer (SET) generating frustrated radical pairs could also play an important role. These highly reactive radical species typically have significantly higher energy than the FLP, which prompted this investigation into their formation. Herein, we provide evidence that the classical phosphine/borane combinations PMes3 /B(C6 F5 )3 and PtBu3 /B(C6 F5 )3 both form an electron donor-acceptor (charge-transfer) complex that undergoes visible-light-induced SET to form the corresponding highly reactive radical-ion pairs. Subsequently, we show that by tuning the properties of the Lewis acid/base pair, the energy required for SET can be reduced to become thermally accessible.

Performance of TDDFT Vertical Excitation Energies of Core-Substituted Naphthalene Diimides.

We have evaluated the performance of various density functionals, covering generalized gradient approximation (GGA), global hybrid (GH) and range-separated hybrid (RSH), using time dependent density functional theory (TDDFT) for computing vertical excitation energies against experimental absorption maximum (λmax ) for a set of 10 different core-substituted naphthalene diimides (cNDI) recorded in dichloromethane. The computed excitation in case of GH PBE0 is most accurate while the trend is most systematic with RSH LCY-BLYP compared to λmax . We highlight the importance of including solvent effects for optimal agreement with the λmax . Increasing the basis set size from TZ2P to QZ4P has a negligible influence on the computed excitation energies. Notably, RSH CAMY-B3LYP gave the least error for charge-transfer excitation. The poorest agreement with λmax is obtained with semi-local GGA functionals. Use of the optimally-tuned RSH LCY-BLYP* is not recommended because of the high computational cost and marginal improvement in results.

Distortion-Controlled Redshift of Organic Dye Molecules.

It is shown, quantum chemically, how structural distortion of an aromatic dye molecule can be leveraged to rationally tune its optoelectronic properties. By using a quantitative Kohn-Sham molecular orbital (KS-MO) approach, in combination with time-dependent DFT (TD-DFT), the influence of various structural and electronic tuning parameters on the HOMO-LUMO gap of a benzenoid model dye have been investigated. These parameters include 1) out-of-plane bending of the aromatic core, 2) bending of the bridge with respect to the core, 3) the nature of the bridge itself, and 4) π-π stacking. The study reveals the coupling of multiple structural distortions as a function of bridge length and number of bridges in benzene to be chiefly responsible for a decreased HOMO-LUMO gap, and consequently, red-shifting of the absorption wavelength associated with the lowest singlet excitation (λ≈560 nm) in the model cyclophane systems. These physical insights together with a rational approach for tuning the oscillator strength were leveraged for the proof-of-concept design of an intense near-infrared (NIR) absorbing cyclophane dye at λ=785 nm. This design may contribute to a new class of distortion-controlled NIR absorbing organic dye molecules.

New Insights in Frustrated Lewis Pair Chemistry with Azides.

The geminal frustrated Lewis pair (FLP) tBu2 PCH2 BPh2 (1) reacts with phenyl-, mesityl-, and tert-butyl azide affording, respectively, six, five, and four-membered rings as isolable products. DFT calculations revealed that the formation of all products proceeds via the six-membered ring structure, which is thermally stable with an N-phenyl group, but rearranges when sterically more encumbered Mes-N3 and tBu-N3 are used. The reaction of 1 with Me3 Si-N3 is believed to follow the same course, yet subsequent N2 elimination occurs to afford a four-membered heterocycle (5), which can be considered as a formal FLP-trimethylsilylnitrene adduct. Compound 5 reacts with hydrochloric acid or tetramethylammonium fluoride and showed frustrated Lewis pair reactivity towards phenylisocyanate.

Pyridyl-Functionalized 1-Phosphabarrelene: Synthesis, Coordination Chemistry and Photochemical di-π-Methane Rearrangement.

The [4+2] cycloaddition of 2-(2'-pyridyl)-4,6-diphenyl-λ3 -phosphinine with the highly reactive dienophile hexafluoro-2-butyne has been studied and the first pyridyl-functionalized 1-phosphabarrelene was obtained and structurally characterized. Although monodentate CF3 -1-phosphabarrelenes show only a poor coordination ability, the chelating nature of the novel P,N-hybrid ligand gives access to various transition-metal complexes. Upon irradiation with UV light, the pyridyl-functionalized 1-phosphabarrelene undergoes a rather selective di-π-methane rearrangement in the coordination sphere of the metal center, leading to the formation of a complex based on a hitherto unknown pyridyl-functionalized 5-phosphasemibullvalene derivative. DFT calculations provide first insights into the mechanism of this reaction.

Parallels between Metal-Ligand Cooperativity and Frustrated Lewis Pairs.

Metal ligand cooperativity (MLC) and frustrated Lewis pair (FLP) chemistry both feature the cooperative action of a Lewis acidic and a Lewis basic site on a substrate. A lot of work has been carried out in the field of FLPs to prevent Lewis adduct formation, which often reduces the FLP reactivity. Parallels are drawn between the two systems by looking at their reactivity with CO2, and we explore the role of steric bulk in preventing dimer formation in MLC systems.

Phosphinine-Based Ligands in Gold-Catalyzed Reactions.

A series of substituted phosphinines, 1-phosphabarrelenes and 5-phosphasemibullvalenes were synthesized and evaluated for their potential application as ligands in homogeneous catalytic reactions. While their buried volume (%Vbur ) was calculated to get insight into the steric properties, [LNi(CO)3 ] complexes were prepared in order to determine the corresponding Tolman electronic parameter. ETS-NOCV (extended-transition-state natural orbital for chemical valence) calculations on [LAuCl] complexes further allowed an estimation of the σ- and π-contributions to the L-M interaction. AuI coordination compounds of selected examples were prepared and characterized by single crystal X-ray diffraction. Finally, the three classes of PIII compounds were successfully used in the AuI -catalyzed cycloisomerization of N-2-propyn-1-ylbenzamide, showing very good activities and selectivities, which are comparable with the reported data of cationic phosphorus-based gold catalysts.

A New Mode of Chemical Reactivity for Metal-Free Hydrogen Activation by Lewis Acidic Boranes.

We herein explore whether tris(aryl)borane Lewis acids are capable of cleaving H2 outside of the usual Lewis acid/base chemistry described by the concept of frustrated Lewis pairs (FLPs). Instead of a Lewis base we use a chemical reductant to generate stable radical anions of two highly hindered boranes: tris(3,5-dinitromesityl)borane and tris(mesityl)borane. NMR spectroscopic characterization reveals that the corresponding borane radical anions activate (cleave) dihydrogen, whilst EPR spectroscopic characterization, supported by computational analysis, reveals the intermediates along the hydrogen activation pathway. This radical-based, redox pathway involves the homolytic cleavage of H2 , in contrast to conventional models of FLP chemistry, which invoke a heterolytic cleavage pathway. This represents a new mode of chemical reactivity for hydrogen activation by borane Lewis acids.

Construction of alkyl-substituted pentaphosphido ligands in the coordination sphere of cobalt.

Rare mono- and diorganopentaphosphido cobalt complexes are accessible by P-P condensation using the unprecedented, reactive cobalt-gallium tetraphosphido complex [K(dme)2{(MesBIAN)Co(µ-η4:η2-P4)Ga(nacnac)}] (2). Compound 2 was prepared in good yield by reaction of [K(Et2O){(MesBIAN)Co(η4-1,5-cod)}] [1, BIAN = bis(mesitylimino)acenaphthene diimine, cod = 1,5-cyclooctadiene] with [Ga(nacnac)(η2-P4)] (nacnac = CH[CMeN(2,6-iPr2C6H3)]2). Reactions with R2PCl (R = iPr, tBu, and Cy) selectively afford [(MesBIAN)Co(cyclo-P5R2)] (3a-c), which feature η4-coordinated 1,1-diorganopentaphosphido ligands. The mechanism of formation of these species has been studied by 31P{1H} NMR spectroscopy and DFT calculations. In the case of 3a (R = iPr), it was possible to identify the intermediate [(MesBIAN)Co(µ-η4:η2-P5iPr2)Ga(nacnac)] (4) by single-crystal X-ray diffraction. A related, monosubstituted organopentaphosphido cobalt complex [(MesBIAN)Co(µ-η4:η1-P5 tBu)GaCl(nacnac)] (5) was isolated by reacting dichloroalkylphosphane tBuPCl2 with 2. Heterobimetallic complexes such as 2 thus may enable the targeted construction of a range of new metal-coordinated polyphosphorus frameworks by P-P condensation.

Rational design of near-infrared absorbing organic dyes: Controlling the HOMO-LUMO gap using quantitative molecular orbital theory.

Principles are presented for the design of functional near-infrared (NIR) organic dye molecules composed of simple donor (D), spacer (π), and acceptor (A) building blocks in a D-π-A fashion. Quantitative Kohn-Sham molecular orbital analysis enables accurate fine-tuning of the electronic properties of the π-conjugated aromatic cores by effecting their size, including silaaromatics, adding donor and acceptor substituents, and manipulating the D-π-A torsional angle. The trends in HOMO-LUMO gaps of the model dyes correlate with the excitation energies computed with time-dependent density functional theory at CAMY-B3LYP. Design principles could be developed from these analyses, which led to a proof-of-concept linear D-π-A with a strong excited-state intramolecular charge transfer and a NIR absorption at 879 nm. © 2018 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.

Chiral Control in Pentacoordinate Systems: The Case of Organosilicates.

Chirality at the central element of pentacoordinate systems can be controlled with two identical bidentate ligands. In such cases the topological Levi-Desargues graph for all the Berry pseudorotations (BPR, max. 20) reduces to interconnected inner and outer "circles" that represent the dynamic enantiomer pair. High enough barriers of the BPR crossovers between the two circles is all what is needed to ascertain chiral integrity. This is illustrated computationally and experimentally for the organosilicates 7 and 10 that carry besides a Me (a), Et (b), Ph (c), or F (d) group two bidentate 2-(phenyl)benzo[ b]-thiophene or 2-(phenyl)naphthyl ligands, respectively. The enantiomers of tetraorganosilane precursor 9 could be separated by column chromatography. Their chiral integrity persisted on forming the silicates. CD spectra are reported for 10c. Fluoro derivative 10d is shown to have its electronegative F substituent in an equatorial position, is stable toward hydrolysis, and its enantiomers do not racemize at ambient temperatures, while those of 10c racemize slowly.

Synthesis of a Cyclic Co2Sn2 Cluster Using a Co- Synthon.

[Ar'SnCo]2 (1, Ar' = C6H3-2,6{C6H3-2,6- iPr2}2), a rare metal-metal bonded cobalt-tin cluster with low-coordinate tin atoms, was prepared by the reaction of [K(thf)0.2][Co(1,5-cod)2] (cod = 1,5-cyclooctadiene) with [Ar'Sn(µ-Cl)]2. This reaction illustrates a promising synthetic strategy to access uncommon metal clusters. The structure of 1 features a rhomboidal Co2Sn2 core with strong metal-metal bonds between tin and cobalt and a weaker tin-tin interaction. Reaction of 1 with white phosphorus afforded [Ar'2Sn2Co2P4] (2), the first molecular cluster compound containing phosphorus, cobalt and tin.

Aryldiazonium Salts as Nitrogen-Based Lewis Acids: Facile Synthesis of Tuneable Azophosphonium Salts.

Inspired by the commercially available azoimidazolium dyes (e.g., Basic Red 51) that can be obtained from aryldiazonium salts and N-heterocyclic carbenes, we developed the synthesis of a unique set of arylazophosphonium salts. A range of colours were obtained by applying readily tuneable phosphine donor ligands and para-substituted aryldiazonium salts as nitrogen-based Lewis acids. With cyclic voltammetry, a general procedure was designed to establish whether the reaction between a Lewis acid and a Lewis base occurs by single-electron transfer or electron-pair transfer.

Template-Directed Synthesis of an Inverted Spiro Architecture.

The regular bicyclic spiro motif is highly abundant given its synthetic accessibility while the diastereomer-virtually obtained through inversion at the central atom-is almost unknown. We have developed methodology to access the elusive inverted spiro architecture by employing a covalent template-directed approach. Comparison with the regular spiro bicycle analog unequivocally established the diastereomeric relationship, providing insight into the fascinating stereochemical and structural properties.

Ring-opening of Epoxides Mediated by Frustrated Lewis Pairs.

Treatment of the preorganized frustrated Lewis pairs (FLPs) tBu2 PCH2 BPh2 (1) and o-Ph2 P(C6 H4 )BCat (Cat=catechol) (4) with 2-methyloxirane, 2-phenyloxirane and 2-(trifluoromethyl)oxirane resulted in epoxide ring-opening to yield the six- and seven-membered heterocycles 2 a-c and 5 a-c, respectively. These zwitterionic products were characterized spectroscopically, and compounds 2 a, 2 b, 5 a and 5 c were structurally characterized by single-crystal X-ray structure analyses. Based on computational and kinetic studies, the mechanism of these reactions was found to proceed via activation of the epoxide by the Lewis acidic borane moiety followed by nucleophilic attack of the phosphine of a second FLP molecule. The resulting chain-like intermediates afford the final cyclic products by ring-closure and concurrent release of the second equivalent of FLP that behaves as catalyst in this reaction.