An efficient one-pot synthesis of carbazole fused benzoquinolines and pyridocarbazoles

Cobalt­(II), in the presence of acetate and nitrate, quantitatively adds to the manganese–cobalt oxido cubane Mn^IVCo^III₃O₄(OAc)₅(py)₃ (<b>1</b>) to furnish the pentametallic dangler complex Mn^IVCo^III₃Co^IIO₄(OAc)₆(NO₃)­(py)₃ (<b>2</b>). Complex <b>2</b> is structurally reminiscent of photosystem II’s oxygen-evolving center, and is a rare example of a transition-metal “dangler” complex. Superconducting quantum interference device magnetometry and density functional theory calculations characterize <b>2</b> as having an <i>S</i> = 0 ground state arising from antiferromagnetic coupling between the Co^II and Mn^IV ions. At higher temperatures, an uncoupled state dominates. The voltammogram of <b>2</b> has four electrochemical events, two more than that of its parent cubane <b>1</b>, suggesting that addition of the dangler increases available redox states. Structural, electrochemical, and magnetic comparisons of complexes <b>1</b> and <b>2</b> allow a better understanding of the dangler’s influence on a cubane

Concerted Cycloaddition Mechanism in the CuAAC Reaction Catalyzed by 1,8-Naphthyridine Dicopper Complexes

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most versatile reactions in the “click chemistry” toolbox, and its development has made the synthesis of 1,4-triazole derivatives robust and efficient. In this work, we present a density functional theory (DFT) study on the mechanism of the CuAAC reaction catalyzed by a dicopper complex supported by a nonsymmetric 1,8-naphtyridine ligand bearing two different metal-coordinating substituents (i.e., −P­(tBu)2 and −C­(Me)­(Py)2). The calculations showed that the cycloaddition of the azide to the alkyne occurs in a single concerted step, in contrast with the two-step mechanism proposed in the literature. The energies predicted for this step indicated that the 1,4-triazole isomer of the product is formed in a selective manner, in agreement with experiments. Further, the DFT results showed that there is a subtle and complex interplay between several variables, including the relative orientation of the two substrates, the position of the counter-anion, and the partial decoordination of the 1,8-naphtyridine ligand. A series of 90 transition state calculations showed that, on average, the impact of these variables is strong on the structures but soft on the energy barriers, highlighting the flexible nature of the bonding within the coordination sphere of the bimetallic core of the catalyst. The insight provided by this study will be valuable for the further development of dicopper catalysts for the CuAAC reaction

Concerted Cycloaddition Mechanism in the CuAAC Reaction Catalyzed by 1,8-Naphthyridine Dicopper Complexes

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most versatile reactions in the “click chemistry” toolbox, and its development has made the synthesis of 1,4-triazole derivatives robust and efficient. In this work, we present a density functional theory (DFT) study on the mechanism of the CuAAC reaction catalyzed by a dicopper complex supported by a nonsymmetric 1,8-naphtyridine ligand bearing two different metal-coordinating substituents (i.e., −P­(tBu)2 and −C­(Me)­(Py)2). The calculations showed that the cycloaddition of the azide to the alkyne occurs in a single concerted step, in contrast with the two-step mechanism proposed in the literature. The energies predicted for this step indicated that the 1,4-triazole isomer of the product is formed in a selective manner, in agreement with experiments. Further, the DFT results showed that there is a subtle and complex interplay between several variables, including the relative orientation of the two substrates, the position of the counter-anion, and the partial decoordination of the 1,8-naphtyridine ligand. A series of 90 transition state calculations showed that, on average, the impact of these variables is strong on the structures but soft on the energy barriers, highlighting the flexible nature of the bonding within the coordination sphere of the bimetallic core of the catalyst. The insight provided by this study will be valuable for the further development of dicopper catalysts for the CuAAC reaction

Density Functional Study on the Mechanism of the Vanadium-Catalyzed Oxidation of Sulfides by Hydrogen Peroxide

A computational study with the Becke3LYP method is carried out on the mechanism of the reaction of complexes V(O)(L)(OOH) and V(O)(LH)(OO) (L = O(CH)3N(CH2)2O) with CH3S−SCH3, a system that stands as a model for experimental systems where the metal complex contains larger chelating Schiff bases and the substrate is bis(tert-butyl) disulfide. The different possible isomers of both the hydroperoxo V(O)(L)(OOH) and the peroxo V(O)(LH)(OO) forms of the catalyst are explored, and the reactivity of the most stable among them with the dimethyl disulfide substrate is studied through location of the corresponding transition states. A large variety of reactive paths happen to exist, though in all cases the reaction takes place through a direct transfer process, with the simultaneous formation of the S−O bond and breaking of the O−O bond being the rate-limiting step

Computational Rationalization of the Dependence of the Enantioselectivity on the Nature of the Catalyst in the Vanadium-Catalyzed Oxidation of Sulfides by Hydrogen Peroxide

A computational study with the IMOMM(Becke3LYP:MM3) method is carried out on the mechanism of the enantioselective reaction of complex V(O)(L)(OOH), L= bulky tridentate Schiff base, and bis(tert-butyl) disulfide. The reaction with a given L ligand A is first systematically studied:  different conformers of the catalyst are optimized, and the large number of associated transition states are systematically searched. The study is then extended to the geometry optimization of selected transition states associated to other ligands B, C, and D, similar to A but differing in the nature of certain substituents R1, R2, R3. The experimental trends in selectivity for catalysts based on ligands A to D are faithfully reproduced by the calculations. Analysis of the computational results leads finally to the formulation of a simple model that can explain one of the most remarkable aspect of this reaction, namely the large effect on enantioselectivity of ligands seemingly far from each other in the catalyst

Base-Catalyzed Inversion of Chiral Sulfur Centers. A Computational Study

A theoretical study on the pyramidal inversion of the chiral sulfur compounds SO(X)(Me) (X = Cl, OMe, p-MePh) has been carried out by means of the DFT(Becke3LYP) method. Our results reveal that in the case of X = Cl, an organic tertiary amine such as NMe3 can catalyze the racemization. The base-catalyzed inversion of SO(Cl)(Me) is proposed as a feasible dynamic kinetic resolution mechanism for the synthesis of chiral sulfoxides by the DAG method

Synthetic and Computational Studies on the Rhodium-Catalyzed Hydroamination of Aminoalkenes

The influence of ligand structure on rhodium-catalyzed hydroamination has been evaluated for a series of phosphinoarene ligands. These catalysts have been evaluated in a set of catalytic intramolecular Markovnikov hydroamination reactions. The mechanism of hydroamination catalyzed by the rhodium­(I) complexes in this study was examined computationally, and the turnover-limiting step was elucidated. These computational studies were extended to a series of theoretical hydroamination catalysts to compare the electronic effects of the ancillary ligand substituents. The relative energies of intermediates and transition states were compared to those of intermediates in the reaction catalyzed by the unsubstituted catalyst. The experimental difference in the reactivities of electron-rich and electron-poor catalysts was compared to the computational results, and it was found that the activity for the electron-poor catalysts predicted from the reaction barriers was overestimated. Thus, the analysis of the catalysts in this study was expanded to include the binding preference of each ligand, in comparison to that of the unsubstituted ligand. This information accounts for the disparity between observed reactivity and the calculated overall reaction barrier for electron-poor ligands. The ligand-binding preferences for new ligand structures were calculated, and ligands that were predicted to bind strongly to rhodium generated catalysts for the experimental catalytic reactions that were more reactive than those predicted to bind more weakly

Synthetic and Computational Studies on the Rhodium-Catalyzed Hydroamination of Aminoalkenes

The influence of ligand structure on rhodium-catalyzed hydroamination has been evaluated for a series of phosphinoarene ligands. These catalysts have been evaluated in a set of catalytic intramolecular Markovnikov hydroamination reactions. The mechanism of hydroamination catalyzed by the rhodium­(I) complexes in this study was examined computationally, and the turnover-limiting step was elucidated. These computational studies were extended to a series of theoretical hydroamination catalysts to compare the electronic effects of the ancillary ligand substituents. The relative energies of intermediates and transition states were compared to those of intermediates in the reaction catalyzed by the unsubstituted catalyst. The experimental difference in the reactivities of electron-rich and electron-poor catalysts was compared to the computational results, and it was found that the activity for the electron-poor catalysts predicted from the reaction barriers was overestimated. Thus, the analysis of the catalysts in this study was expanded to include the binding preference of each ligand, in comparison to that of the unsubstituted ligand. This information accounts for the disparity between observed reactivity and the calculated overall reaction barrier for electron-poor ligands. The ligand-binding preferences for new ligand structures were calculated, and ligands that were predicted to bind strongly to rhodium generated catalysts for the experimental catalytic reactions that were more reactive than those predicted to bind more weakly

Quantum chemical modeling of the reaction path of chorismate mutase based on the experimental substrate/product complex

Chorismate mutase is a well‐known model enzyme, catalyzing the Claisen rearrangement of chorismate to prephenate. Recent high‐resolution crystal structures along the reaction coordinate of this enzyme enabled computational analyses at unprecedented detail. Using quantum chemical simulations, we investigated how the catalytic reaction mechanism is affected by electrostatic and hydrogen‐bond interactions. Our calculations showed that the transition state (TS) was mainly stabilized electrostatically, with Arg90 playing the leading role. The effect was augmented by selective hydrogen‐bond formation to the TS in the wild‐type enzyme, facilitated by a small‐scale local induced fit. We further identified a previously underappreciated water molecule, which separates the negative charges during the reaction. The analysis includes the wild‐type enzyme and a non‐natural enzyme variant, where the catalytic arginine was replaced with an isosteric citrulline residue

Polyene Cyclization by a Double Intramolecular Heck Reaction. A DFT Study

A density functional theory (DFT) model study has been carried out on the cyclization of aryl polyene triflate catalyzed by a Pd(II)-BINAP complex in a Heck type reaction. In the model study, the catalyst was represented by Pd(PH2(CH)4PH2), whereas the aryl polyene triflate substrate was simplified by replacing the dimethoxy naphthalene fragment with hydrogens. Formally, this cyclization reaction consists of an intramolecular Heck reaction with two olefin insertions, also known as a double or cascade Heck reaction. The postulated cationic pathway for aryl triflate substrates has been explored as the reaction mechanism. The study has mainly focused on the two migratory insertion steps, where the identity of the final reaction products is decided. At both steps two distinct insertions may occur:  exo, or 1,2-insertion, and endo, or 2,1-insertion. The computation of the possible intermediates and transition states demonstrated that the first insertion is exo-selective, with an energy barrier of only 4.1 kcal/mol, while the second insertion is endo-selective, involving a much higher energy barrier of 22.8 kcal/mol. The calculated subsequent preference for exo and endo selectivity is in good agreement with qualitative experimental observation. According to our results, the main factor controlling the exo/endo selectivity, at both the thermodynamic and the kinetic levels, is the relative stability of the cyclic system resulting from the migratory insertion. Furthermore, a furan ring present in the substrate can play an important role by forming a stable and inert π-complex that is able to suppress subsequent migratory insertion steps. On the other hand, taking into account the solvent effects using a continuum model, we found that the exo/endo selectivity of the first insertion step is solvent-dependent. As the polarity of the solvent increases, the relative stability of the endo intermediate also increases, in good agreement with the available experimental data. The β-elimination steps affording the final reaction products were also investigated. The results show that the β-elimination on the endo intermediates is thermodynamically favored over the β-elimination on the exo intermediates. On the other hand, the results for the β-elimination on the endo intermediates show that this reaction is highly reversible