Decarboxylative Palladium(II)‐Catalyzed Synthesis of Aryl Amidines from Aryl Carboxylic Acids: Development and Mechanistic Investigation

A fast and convenient synthesis of aryl amidines starting from carboxylic acids and cyanamides is reported. The reaction was achieved by palladium(II)‐catalysis in a one‐step microwave protocol using [Pd(O₂CCF₃)₂], 6‐methyl‐2,2′‐bipyridyl and trifluoroacetic acid (TFA) in N‐methylpyrrolidinone (NMP), providing the corresponding aryl amidines in moderate to excellent yields. The protocol is very robust with regards to the cyanamide coupling partner but requires electron‐rich ortho‐substituted aryl carboxylic acids. Mechanistic insight was provided by a DFT investigation and direct ESI‐MS studies of the reaction. The results of the DFT study correlated well with the experimental findings and, together with the ESI‐MS study, support the suggested mechanism. Furthermore, a scale‐out (scale‐up) was performed with a non‐resonant microwave continuous‐flow system, achieving a maximum throughput of 11 mmol h^?1 by using a glass reactor with an inner diameter of 3 mm at a flow rate of 1 mL min^?1.     

The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

Biginelli reactions have been monitored by direct infusion electrospray ionization mass spectrometry (ESI‐MS) and key cationic intermediates involved in this three‐component reaction have been intercepted and further characterized by tandem MS experiments (ESI‐MS/MS). Density functional theory calculations were also used to investigate the feasibility of the major competing mechanisms proposed for the Biginelli reaction. The experimental and theoretical results were found to corroborate the iminium mechanism proposed by Folkers and Johnson, whereas no intermediates directly associated with either the more energy demanding Knoevenagel or enamine mechanisms could be intercepted.     

Fluoro‐ and Perfluoralkylsulfonylpentafluoroanilides: Synthesis and Characterization of NH Acids for Weakly Coordinating Anions and Their Gas‐Phase and Solution Acidities

Fluoro‐ and perfluoralkylsulfonyl pentafluoroanilides [HN(C₆F₅)(SO₂X); X=F, CF₃, C₄F₉, C₈F₁₇] are a class of imides with two different strongly electron‐withdrawing substituents attached to a nitrogen atom. They are NH acids, the unsymmetrical hybrids of the well‐known symmetrical bissulfonylimides and bispentafluorophenylamine. The syntheses, the structures of these perfluoroanilides, their solvates, and some selected lithium salts give rise to a structural variety beyond the symmetrical parent compounds. The acidities of representative subsets of these novel NH acids have been investigated experimentally and quantum‐chemically and their gas‐phase acidities (GAs) are reported, as well as the pK_a values of these compounds in acetonitrile (MeCN) and DMSO solution. In quantum chemical investigations with the vertical and relaxed COSMO cluster‐continuum models (vCCC/rCCC), the unusual situation is encountered that the DMSO‐solvated acid Me₂SO–H‐N(SO₂CF₃)₂, optimized in the gas phase (vCCC model), dissociates to Me₂SO‐H⁺–N(SO₂CF₃)₂^? during structural relaxation and full optimization with the solvation model turned on (rCCC model). This proton transfer underlines the extremely high acidity of HN(SO₂CF₃)₂. The importance of this effect is studied computationally in DMSO and MeCN solution. Usually this effect is less pronounced in MeCN and is of higher importance in the more basic solvent DMSO. Nevertheless, the neglect of the structural relaxation upon solvation causes typical changes in the computational pK_a values of 1 to 4 orders of magnitude (4–20 kJ mol^?1). The results provide evidence that the published experimental DMSO pK_a value of HN(SO₂CF₃)₂ should rather be interpreted as the pK_a of a Me₂SO‐H⁺–N(SO₂CF₃)₂^? contact ion pair.     

The phenoxy/phenol/copper cation: a minimalistic model of bonding relations in active centers of mononuclear copper enzymes

The "bare" complex [Cu(PhOH)(PhO)](+) with a phenol (PhOH) and a phenoxy (PhO) ligand bound to copper is studied both experimentally and computationally. The binding energies and structure of this complex are probed by mass spectrometry, infrared multi-photon dissociation, and DFT calculations. Further, the monoligated complexes [Cu(PhO)](+) and [Cu(PhOH)](+) are investigated for comparison. DFT calculations on the [Cu(PhOH)(PhO)](+) complex predict that a phenolate anion interacts with copper(II) preferentially through the oxygen atom, and the bonding is associated with electron transfer to the metal center resulting in location of the unpaired electron at the aromatic moiety. Neutral phenol, on the other hand, interacts with copper preferentially through the aromatic ring. The same arrangements are also found in the monoligated complexes [Cu(PhO)](+) and [Cu(PhOH)](+). The calculations further indicate that the bond strength between the copper atom and the oxygen atom of the phenoxy radical is weakened by the presence of neutral phenol from 2.6 eV in bare [Cu(PhO)](+) to 2.1 eV in [Cu(PhOH)(PhO)](+).     

From an Icosahedron to a Plane: Flattening Dodecaiodo‐dodecaborate by Successive Stripping of Iodine

It has been shown by electrospray ionization–ion‐trap mass spectrometry that B₁₂I₁₂^2? converts to an intact B₁₂ cluster as a result of successive stripping of single iodine radicals or ions. Herein, the structure and stability of all intermediate B₁₂I_n^? species (n=11 to 1) determined by means of first‐principles calculations are reported. The initial predominant loss of an iodine radical occurs most probably via the triplet state of B₁₂I₁₂^2?, and the reaction path for loss of an iodide ion from the singlet state crosses that from the triplet state. Experimentally, the boron clusters resulting from B₁₂I₁₂^2? through loss of either iodide or iodine occur at the same excitation energy in the ion trap. It is shown that the icosahedral B₁₂ unit commonly observed in dodecaborate compounds is destabilized while losing iodine. The boron framework opens to nonicosahedral structures with five to seven iodine atoms left. The temperature of the ions has a considerable influence on the relative stability near the opening of the clusters. The most stable structures with five to seven iodine atoms are neither planar nor icosahedral.     

产物可用电喷雾质谱检测的氨基酸/肽季铵化新方法

氨基酸和肽中氨基的化学修饰反应,如乙酰化反应和烷基化反应已被广泛用于蛋白组学研究中蛋白质的定量分析．氨基酸和肽的季铵化产物具有独特的优点,在电喷雾质谱中具有很好的离子化效率,可大大提高检测的灵敏度．文献[6～8]报道的氨基酸和肽的季铵化方法均使用高浓度的盐(如KHCO3),严重影响了质谱的检测结果,难以直接用于蛋白质组学研究．     

On the Exciton Coupling between Two Chlorophyll Pigments in the Absence of a Protein Environment: Intrinsic Effects Revealed by Theory and Experiment

Exciton coupling between two or more chlorophyll (Chl) pigments is a key mechanism associated with the color tuning of photosynthetic proteins but it is difficult to disentangle this effect from shifts that are due to the protein microenvironment. Herein, we report the formation of the simplest coupled system, the Chl a dimer, tagged with a quaternary ammonium ion by electrospray ionization. Based on action spectroscopic studies in vacuo, the dimer complexes were found to absorb 50–70 meV to the red of the monomers under the same conditions. First‐principles calculations predict shifts that somewhat depend on the relative orientation of the two Chl units, namely 50 and 30 meV for structures where the Chl rings are stacked and unstacked, respectively. Our work demonstrates that Chl association alone can produce a large portion of the color shift observed in photosynthetic macromolecular assemblies.     

Iron Borohydride Pincer Complexes for the Efficient Hydrogenation of Ketones under Mild,Base‐Free Conditions: Synthesis and Mechanistic Insight

The new, structurally characterized hydrido carbonyl tetrahydridoborate iron pincer complex [(iPr‐PNP)Fe(H)(CO)(η¹‐BH₄)] ( 1 ) catalyzes the base‐free hydrogenation of ketones to their corresponding alcohols employing only 4.1 atm hydrogen pressure. Turnover numbers up to 1980 at complete conversion of ketone were reached with this system. Treatment of 1 with aniline (as a BH₃ scavenger) resulted in a mixture of trans‐[(iPr‐PNP)Fe(H)₂(CO)] ( 4 a ) and cis‐[(iPr‐PNP)Fe(H)₂(CO)] ( 4 b ). The dihydrido complexes 4 a and 4 b do not react with acetophenone or benzaldehyde, indicating that these complexes are not intermediates in the catalytic reduction of ketones. NMR studies indicate that the tetrahydridoborate ligand in 1 dissociates prior to ketone reduction. DFT calculations show that the mechanism of the iron‐catalyzed hydrogenation of ketones involves alcohol‐assisted aromatization of the dearomatized complex [(iPr‐PNP*)Fe(H)(CO)] ( 7 ) to initially give the Fe⁰ complex [(iPr‐PNP)Fe(CO)] ( 21 ) and subsequently [(iPr‐PNP)Fe(CO)(EtOH)] ( 38 ). Concerted coordination of acetophenone and dual hydrogen‐atom transfer from the PNP arm and the coordinated ethanol to, respectively, the carbonyl carbon and oxygen atoms, leads to the dearomatized complex [(iPr‐PNP*)Fe(CO)(EtO)(MeCH(OH)Ph)] ( 32 ). The catalyst is regenerated by release of 1‐phenylethanol, followed by dihydrogen coordination and proton transfer to the coordinated ethoxide ligand.     

Electrospray Ionization Mass Spectrometry (ESI-MS) as a Useful Tool for Fast Evaluation of Anion and Cation Complexation Abilities of a Cyclam Derivative

Electrospray ionization mass espectrometry (ESI-MS) has been used for the study of a cyclam derivative noncovalent interactions. At acidic pH, diprotonated macrocycle bound to different anionic species were observed. The selectivity shown by competitive experiments is rationalized with the help of semiempirical theoretical calculations. At basic pH, the base peak corresponded to the macrocycle-alkaline metal complexes, and again competition experiments showed different binding strength. Finally, experiments carried out in the presence of transition metal salts allowed the detection of the complexes present in the mixture and revealed their different kinetic behavior.     

Calixarenes as hosts for ammonium cations: a quantum chemical study and mass-spectrometric investigations

Host-guest complexes of tetramethylcavitand with different ammonium cations were investigated by using a quantum chemical method at the density functional level (BP86, B3 LYP). The NH4+ cation is strongly bound to the host. Increasing methyl substitution at the cation decreases its inclination towards the complex formation. The calculated data are in line with results from electrospray ionization mass spectrometry (ESI-MS) experiments. They reveal stable aggregates only for the NH4+ cation and for the primary alkylammonium cations.