Mechanistic Insight into the Cu-Catalyzed C-S Cross-Coupling of Thioacetate with Aryl Halides: A Joint Experimental-Computational Study.

The mechanism of the Ullmann-type reaction between potassium thioacetate (KSAc) and iodobenzene (PhI) catalyzed by CuI associated with 1,10-phenanthroline (phen) as a ligand was explored experimentally and computationally. The study on C-S bond formation was investigated by UV-visible spectrophotometry, cyclic voltammetry, mass spectrometry, and products assessment from radical probes. The results indicate that under experimental conditions the catalytically active species is [Cu(phen)(SAc)] regardless of the copper source. An examination of the aryl halide activation mechanism using radical probes was undertaken. No evidence of the presence of radical species was found during the reaction process, which is consistent with an oxidative addition cross-coupling pathway. The different reaction pathways leading to the experimentally observed reaction products were studied by DFT calculation. The oxidative addition-reductive elimination mechanism via an unstable CuIII intermediate is energetically more feasible than other possible mechanisms such as single electron transfer, halogen atom transfer, and σ-bond methatesis.

Nucleophilic substitution in ionizable Fischer thiocarbene complexes: steric effect of the alkyl substituent on the heteroatom.

A detailed kinetic study has been carried out for the aminolysis of ionizable Fischer thiocarbene complexes (CO)5M[double bond, length as m-dash]C(SR)CH3 (M = Cr, W; R = iPr, nBu, cHex, tBu) with five primary amines and one secondary amine in aqueous acetonitrile solutions (50% MeCN-50% water (v/v)). The observed rate constants for the reaction with primary amines showed a first-order dependence on the amine concentration, while with morpholine, the rate constant has second-order dependence. The general base catalysis process was confirmed by the variation of the rate constants with the concentration of an external catalyst and the pH. The results agree with a stepwise mechanism where the nucleophilic addition to the carbene carbon to produce a tetrahedral intermediate (T±) is the first step, followed by a rapid deprotonation of to form the anion T- which leads to the products by general-acid catalysed leaving group (-SR) expulsion. In general, it was found that the chromium complexes are less reactive than the tungsten analogues. The obtained Brønsted parameters for the nucleophilic addition (ßnuc) indicate that C-N bond formation has made little progress at the transition state. By using Charton's correlation, the role that the steric factor plays throughout the mechanism has been unraveled. The nucleophilic addition to the thiocarbenes is less sensitive to steric effects than the alkoxycarbenes regardless of the nature of the metal centre. Conversely, the steric effects on the general-base catalysis can be strong depending on the volume of the catalyst and the metal centre. On the basis of the structure-reactivity coefficients ß and ψ and comparison with alkoxycarbene complexes, esters and thiolesters, insights into the main factors ruling the reactivity in terms of transition state imbalances are discussed.

Photoremoval of protecting groups: mechanistic aspects of 1,3-dithiane conversion to a carbonyl group.

Photodeprotection of 1,3-dithianes in the presence of thiapyrylium was performed to return to the parent carbonyl compound, and the mechanism was studied by steady state photolysis, laser flash photolysis, and theoretical calculations. Electron transfer from dithianes to triplet sensitizers is extremely fast, and the decay of dithiane radical cations was not affected by the presence of water or oxygen as the consequence of a favorable unimolecular fragmentation pathway. Similar behaviors were observed for dithianes bearing electron-releasing or electron-withdrawing substituents on the aryl moiety, evidenced by C-S bond cleavage to form a distonic radical cation species. The lack of reaction under nitrogen atmosphere, requirement of oxygen for good conversion yields, inhibition of the photodeprotection process by the presence of p-benzoquinone, and absence of a labeled carbonyl final product when the reaction is performed in the presence of H2(18)O all suggest that the superoxide anion drives the deprotection reaction. Density functional theory computational studies on the reactions with water, molecular oxygen, and the superoxide radical anion support the experimental findings.

Cyclic trinuclear copper(I), silver(I), and gold(I) complexes: a theoretical insight.

The metal-ligand, M-L, bonding situation in cyclic trinuclear complexes, CTCs, of copper(I), silver(I), and gold(I) was investigated in terms of the energy decomposition analysis (EDA-NOCV) and natural bond orbitals (NBOs). The anisotropy of the induced current density (ACID) and magnetic response were employed to evaluate the effect of electronic conjugation and metal-metal interactions in CTCs. The EDA-NOCV results show that the M-L bonding is stronger in gold(I) than in copper(I) or silver(I) complexes. Au(+)-L bonds present an elevated covalent character when compared with Cu(+)-L and Ag(+)-L bonds. The NBO analysis confirms the elevated covalent character observed for Au(+)-L bonds, indicating that the ligand-metal donation, L → M, and the metal-ligand back-donation, M → L, are more stabilizing in gold(I) than in copper(I) or silver(I) complexes. Both ACID and the magnetic response calculations reveal that there are cyclic conjugations in the ligands and a strong diatropic ring current indicating the presence of aromaticity. However, there is no through-bond M-L conjugation between the ligands and the metallic centers, as indicated by the absence of a continuous anisotropy boundary surface involving M-L bonds.

Ruthenium(II) complexes of N-heterocyclic carbenes derived from imidazolium-linked cyclophanes.

The present work seeks to characterize, in the light of electronic structure calculations, an unusual metal-[(η(1)-NHC)2:(η(6)-arene)] bonding situation in a set of ruthenium(ii) complexes containing the ortho-xylylene-linked-bis(NHC)cyclophane ligand (NHC-cyclophane) (), which binds to the ruthenium center through two carbene carbons and one of the arene rings. The nature of ruthenium(ii)-[(η(1)-NHC)2:(η(6)-arene)] bonding was investigated in the light of EDA-NOCV, NBO and QTAIM analyses by adopting as a model compound. The interplay between the ortho-cyclophane scaffold with different families of five-membered carbenes, such as imidazole, , triazole-based NHCs (Enders' carbenes), , and P-heterocyclic carbenes (PHCs), , was investigated. The metal-[(η(1)-NHC)2:(η(6)-arene)] bonding situation was also extended to heavier analogues, such as N-heterocyclic silylenes (NHSi) and N-heterocyclic germylenes (NHGe), in order to address how the basicity of NHC, NHSi and NHGe is affected by the cyclophane framework. The results reveal that ruthenium(ii)-[(η(1)-NHC)2:(η(6)-arene)] is more covalently than electrostatically bonded and that the degree of covalence is larger in PHCs than in NHCs or Enders' carbenes. It is also revealed that the covalent character in the ruthenium(ii)-[(η(1)-NHGe)2:(η(6)-arene)] and ruthenium(ii)-[(η(1)-NHSi)2:(η(6)-arene)] bonds is larger than in ruthenium(ii)-[(η(1)-NHC)2:(η(6)-arene)].

Mechanism of the aminolysis of Fischer alkoxy and thiocarbene complexes: a DFT study.

B3LYP calculations have been carried out to study the reaction mechanism of the aminolysis of Fischer carbene complexes of the type (CO)(5)Cr=C(XMe)R (X = O and S; R = Me and Ph). We have explored different possible reaction mechanisms either through neutral or zwitterionic intermediates as well as a general base catalysis assisted by an ammonia molecule. Our results show that the most favorable pathway for the aminolysis of Fischer carbene complexes is through a stepwise reaction via a zwitterionic intermediate generated by the initial nucleophilic attack. We have found that the ammonia-catalyzed mechanism entails a significantly lower barrier for the rate-determining step than the uncatalyzed one. At lower pressure gas-phase conditions, the rate-determining step corresponds to the concerted proton transfer and MeXH elimination. Thiocarbene complexes show a higher energy barrier for this rate-determining step due to the lower basicity of the MeS(-) substituent. At higher pressure or in solution, the rate-determining step corresponds to the initial nucleophilic attack. Our results indicate that the transition state of the nucleophilic attack is more advanced and has a higher barrier for alkoxycarbene than thiocarbene complexes due to the stronger pi-donor character of the alkoxy group that reduces the electrophilicity of the attacked carbene atom making the nucleophilic attack more difficult.

Role of the hydrophobicity on the thermodynamic and kinetic acidity of Fischer thiocarbene complexes.

Rate constants for the reversible deprotonation of (CO)(5)W=C(SR)CH(3) (W-SR) by OH(-), water and a number of primary aliphatic and secondary alicyclic amines, have been determined in 50% MeCN:50% water at 25 degrees C. In addition, solvation energy and proton affinities values for M-SR (M = Cr and W) in the gas phase and in acetonitrile have been computed at DFT level. Although there is not a linear correlation between the calculated proton affinities and the measured pK(a)s, the calculations reveal that when solvent effects are taken into account the substituted compounds studied show differences in their proton affinities. There is a good correlation between the change in cavitation energy (DeltaG(cav)) for the Fischer carbene complexes and log P of the thioalkyl substituents. In proton transfer reactions with amines, steric effects are more important for W complexes with respect to their Cr analogues as a consequence of differences in transition state progress. On the other hand, in reactions with OH(-), hydrophobicity of the R substituent is responsible for the observed changes in intrinsic kinetic acidities, which is supported by the good correlation obtained between log k(0) and log P. W complexes are more sensitive to hydrophobic effects due to the tighter solvation sphere with respect to their Cr counterparts. However, in the limit of log P = 0, the energy involved in the solvent reorganization process is the same regardless of the metal.