A Mechanistic Investigation of the Kinetic Resolution of Secondary Aromatic Alcohols Using a Ferrocene‐Based Planar Chiral 4‐(Dimethylamino)pyridine Catalyst

A detailed computational and kinetic analysis of the acetylation of 1‐phenylethanol with acetic anhydride catalyzed by planar chiral 4‐(dimethylamino)pyridine (DMAP) catalyst (?)‐ 1 is presented. The study includes a computational investigation of the potential‐energy surface including the acylation and stereoselective transition states at the DFT level of theory. Experimentally, the kinetic study shows that the reaction proceeds in a first‐order manner in catalyst, whereas both substrates, acetic anhydride and 1‐phenylethanol, show fractional order, which is in accordance with steady‐state conditions. The fractional order depends on an equilibrium between the free catalyst and the acetylated catalyst.     

Proton Order–Disorder Phenomena in a Hydrogen‐Bonded Rhodium–η5‐Semiquinone Complex: A Possible Dielectric Response Mechanism

A newly synthesized one‐dimensional (1D) hydrogen‐bonded (H‐bonded) rhodium(II)–η⁵‐semiquinone complex, [Cp*Rh(η⁵‐p‐HSQ‐Me₄)]PF₆ ([ 1 ]PF₆; Cp*=1,2,3,4,5‐pentamethylcyclopentadienyl; HSQ=semiquinone) exhibits a paraelectric–antiferroelectric second‐order phase transition at 237.1 K. Neutron and X‐ray crystal structure analyses reveal that the H‐bonded proton is disordered over two sites in the room‐temperature (RT) phase. The phase transition would arise from this proton disorder together with rotation or libration of the Cp* ring and PF₆^? ion. The relative permittivity ε_b′ along the H‐bonded chains reaches relatively high values (ca., 130) in the RT phase. The temperature dependence of ¹³C CP/MAS NMR spectra demonstrates that the proton is dynamically disordered in the RT phase and that the proton exchange has already occurred in the low‐temperature (LT) phase. Rate constants for the proton exchange are estimated to be 10^?4–10^?6 s in the temperature range of 240–270 K. DFT calculations predict that the protonation/deprotonation of [ 1 ]⁺ leads to interesting hapticity changes of the semiquinone ligand accompanied by reduction/oxidation by the π‐bonded rhodium fragment, producing the stable η⁶‐hydroquinone complex, [Cp*Rh³⁺(η⁶‐p‐H₂Q‐Me₄)]²⁺ ([ 2 ]²⁺), and η⁴‐benzoquinone complex, [Cp*Rh⁺(η⁴‐p‐BQ‐Me₄)] ([ 3 ]), respectively. Possible mechanisms leading to the dielectric response are discussed on the basis of the migration of the protonic solitons comprising of [ 2 ]²⁺ and [ 3 ], which would be generated in the H‐bonded chain.     

Supramolecular Recognition Influences Magnetism in [X@HVIV8VV14O54]6− Self‐Assemblies with Symmetry‐Breaking Guest Anions

Mixed‐valence polyoxovanadates(IV/V) have emerged as one of the most intricate class of supramolecular all‐inorganic host species, able to encapsulate a wide variety of smaller guest templates during their self‐assembly formation process. As showcased herein, the incorporation of guests, though governed solely by ultra‐weak electrostatic and van der Waals interactions, can cause drastic effects on the electronic and magnetic characteristics of the shell complex of the polyoxovanadate. We address the question of methodology for the magnetochemical analysis of virtually isostructural {V^IV/V₂₂O₅₄}‐type polyoxoanions of D_2d symmetry enclosing diamagnetic VO₂F₂^? (C_2v), SCN^? (C_∞v), or ClO₄^? (T_d) template anions. These induce different polarization effects related to differences in their geometric structures, symmetry, ion radii, and valence shells, eventually resulting in a supramolecular modulation of magnetic exchange between the V(3d) electrons that are partly delocalized over the {V₂₂O₅₄} shells. We also include the synthesis and characterization of the novel [V^VO₂F₂@HV^IV₈V^V₁₄O₅₄]^6? system that comprises the rarely encountered discrete difluorovanadate anion as a quasi‐isolated guest species.     

Lewis Acids as Activators in CBS‐Catalysed Diels–Alder Reactions: Distortion Induced Lewis Acidity Enhancement of SnCl4

The effect of several Lewis acids on the CBS catalyst (named after Corey, Bakshi and Shibata) was investigated in this study. While ²H NMR spectroscopic measurements served as gauge for the activation capability of the Lewis acids, in situ FT‐IR spectroscopy was employed to assess the catalytic activity of the Lewis acid oxazaborolidine complexes. A correlation was found between the Δδ(²H) values and rate constants k_DA, which indicates a direct translation of Lewis acidity into reactivity of the Lewis acid–CBS complexes. Unexpectedly, a significant deviation was found for SnCl₄ as Lewis acid. The SnCl₄–CBS adduct was much more reactive than the Δδ(²H) values predicted and gave similar reaction rates to those observed for the prominent AlBr₃–CBS adduct. To rationalize these results, quantum mechanical calculations were performed. The frontier molecular orbital approach was applied and a good correlation between the LUMO energies of the Lewis acid–CBS–naphthoquinone adducts and k_DA could be found. For the SnCl₄–CBS–naphthoquinone adduct an unusual distortion was observed leading to an enhanced Lewis acidity. Energy decomposition analysis with natural orbitals for chemical valence (EDA‐NOCV) calculations revealed the relevant interactions and activation mode of SnCl₄ as Lewis acid in Diels–Alder reactions.     

DFT Study of the Molybdenum‐Catalyzed Deoxydehydration of Vicinal Diols

The mechanism of the molybdenum‐catalyzed deoxydehydration (DODH) of vicinal diols has been investigated using density functional theory. The proposed catalytic cycle involves condensation of the diol with an Mo^VI oxo complex, oxidative cleavage of the diol resulting in an Mo^IV complex, and extrusion of the alkene. We have compared the proposed pathway with several alternatives, and the results have been corroborated by comparison with the molybdenum‐catalyzed sulfoxide reduction recently published by Sanz et al. and with experimental observations for the DODH itself. Improved understanding of the mechanism should expedite future optimization of molybdenum‐catalyzed biomass transformations.     

Reduced dimensionality (3,2)D NMR experiments and their automated analysis: implications to high‐throughput structural studies on proteins

Protein NMR spectroscopy has expanded dramatically over the last decade into a powerful tool for the study of their structure, dynamics, and interactions. The primary requirement for all such investigations is sequence‐specific resonance assignment. The demand now is to obtain this information as rapidly as possible and in all types of protein systems, stable/unstable, soluble/insoluble, small/big, structured/unstructured, and so on. In this context, we introduce here two reduced dimensionality experiments – (3,2)D‐hNCO canH and (3,2)D‐hN coCA nH – which enhance the previously described 2D NMR‐based assignment methods quite significantly. Both the experiments can be recorded in just about 2–3 h each and hence would be of immense value for high‐throughput structural proteomics and drug discovery research. The applicability of the method has been demonstrated using alpha‐helical bovine apo calbindin‐D9k P43M mutant (75 aa) protein. Automated assignment of this data using AUTOBA has been presented, which enhances the utility of these experiments. The backbone resonance assignments so derived are utilized to estimate secondary structures and the backbone fold using Web‐based algorithms. Taken together, we believe that the method and the protocol proposed here can be used for routine high‐throughput structural studies of proteins. Copyright © 2014 John Wiley & Sons, Ltd.     

Insights into the Cascade Reaction of CO and Heteroallenes Mediated by Dinitrogen Hafnocene Complexes: The Indirect Effect of Nitride's Nucleophilicity

A DFT mechanistic exploration of the reactivity of the dinitrogen hafnocene complex, [{(η⁵‐C₅H₂‐1,2,4‐Me₃)₂Hf}₂(μ₂‐N₂)], towards mixtures of CO/CO₂ and CO/OCNtBu is reported. The crucial role of the nitride intermediate is highlighted, as well as the importance of the bridging mode of the cyanate ligand between the two Hf metal atoms throughout the process. Interestingly, the CO₂ addition to the nitride intermediate occurs through an outer‐sphere transition state, whereas the addition of the heteroallene is governed by the steric congestion imposed by cyclopentadienyl ligands.     

Mechanism of Insertion Reactions between Silylenoid H2SiLiF and GeH3R (R =F,OH, NH2): a Theoretical Study

Theoretical investigations on the insertion reaction mechanisms of three- membered-ring silylenoid H2 Si Li F with GeH 3R(R = F, OH, NH2) have been systematically carried out by combined density functional theory(DFT) and ab initio quantum chemical calculations. The geometries of all stationary points for these reactions were optimized using the B3 LYP method and then the QCISD method was used to calculate the single-point energies. The calculated results indicate that, there are one precursor complex(Q), one transition state(TS), and one intermediate(IM) which connect the reactants and the products along the potential energy surface. The insertion reactions of three-membered-ring silylenoid with Ge H3 R proceed in a concerted manner, forming H2RSi-Ge H3 and Li F. The calculated potential energy barriers of the three reactions are 29.17, 30.90, and 54.07 k J/mol, and the reaction energies for the three reactions are –127.05, –116.91, and –103.31 k J/mol, respectively. The insertion reactions in solvents are similar to those in vacuum. Under the same situation, the insertion reactions should occur easily in the following order: GeH 3-F GeH 3-OH GeH 3-NH2. The elucidations of the mechanism of these insertion reactions provided a new mode of silicon-germanium bond formation.     

Bio‐Inspired Transition Metal–Organic Hydride Conjugates for Catalysis of Transfer Hydrogenation: Experiment and Theory

Taking inspiration from yeast alcohol dehydrogenase (yADH), a benzimidazolium (BI⁺) organic hydride‐acceptor domain has been coupled with a 1,10‐phenanthroline (phen) metal‐binding domain to afford a novel multifunctional ligand ( L ^BI+) with hydride‐carrier capacity ( L ^BI++H^?? L ^BIH). Complexes of the type [Cp*M( L ^BI)Cl][PF₆]₂ (M=Rh, Ir) have been made and fully characterised by cyclic voltammetry, UV/Vis spectroelectrochemistry, and, for the Ir^III congener, X‐ray crystallography. [Cp*Rh( L ^BI)Cl][PF₆]₂ catalyses the transfer hydrogenation of imines by formate ion in very goods yield under conditions where the corresponding [Cp*Ir( L ^BI)Cl][PF₆] and [Cp*M(phen)Cl][PF₆] (M=Rh, Ir) complexes are almost inert as catalysts. Possible alternatives for the catalysis pathway are canvassed, and the free energies of intermediates and transition states determined by DFT calculations. The DFT study supports a mechanism involving formate‐driven Rh?H formation (90 kJ mol^?1 free‐energy barrier), transfer of hydride between the Rh and BI⁺ centres to generate a tethered benzimidazoline (BIH) hydride donor, binding of imine substrate at Rh, back‐transfer of hydride from the BIH organic hydride donor to the Rh‐activated imine substrate (89 kJ mol^?1 barrier), and exergonic protonation of the metal‐bound amide by formic acid with release of amine product to close the catalytic cycle. Parallels with the mechanism of biological hydride transfer in yADH are discussed.     

Experimental and Theoretical Studies on the Rearrangement of 2‐Oxoazepane α,α‐Amino Acids into 2′‐Oxopiperidine β2,3,3‐Amino Acids: An Example of Intramolecular Catalysis

Enantiopure β‐amino acids represent interesting scaffolds for peptidomimetics, foldamers and bioactive compounds. However, the synthesis of highly substituted analogues is still a major challenge. Herein, we describe the spontaneous rearrangement of 4‐carboxy‐2‐oxoazepane α,α‐amino acids to lead to 2′‐oxopiperidine‐containing β^2,3,3‐amino acids, upon basic or acid hydrolysis of the 2‐oxoazepane α,α‐amino acid ester. Under acidic conditions, a totally stereoselective synthetic route has been developed. The reordering process involved the spontaneous breakdown of an amide bond, which typically requires strong conditions, and the formation of a new bond leading to the six‐membered heterocycle. A quantum mechanical study was carried out to obtain insight into the remarkable ease of this rearrangement, which occurs at room temperature, either in solution or upon storage of the 4‐carboxylic acid substituted 2‐oxoazepane derivatives. This theoretical study suggests that the rearrangement process occurs through a concerted mechanism, in which the energy of the transition states can be lowered by the participation of a catalytic water molecule. Interestingly, it also suggested a role for the carboxylic acid at position 4 of the 2‐oxoazepane ring, which facilitates this rearrangement, participating directly in the intramolecular catalysis.