Activation of hydrogen peroxide by ionic liquids: mechanistic studies and application in the epoxidation of olefins.

Imidazolium-based ionic liquids that contain perrhenate anions are very efficient reaction media for the epoxidation of olefins with H2O2 as an oxidant, thus affording cyclooctene in almost quantitative yields. The mechanism of this reaction does not follow the usual pathway through peroxo complexes, as is the case with long-known molecular transition-metal catalysts. By using in situ Raman, FTIR, and NMR spectroscopy and DFT calculations, we have shown that the formation of hydrogen bonds between the oxidant and perrhenate activates the oxidant, thereby leading to the transfer of an oxygen atom onto the olefin demonstrating the special features of an ionic liquid as a reaction environment. The influence of the imidazolium cation and the oxidant (aqueous H2O2, urea hydrogen peroxide, and tert-butyl hydrogen peroxide) on the efficiency of the epoxidation of cis-cyclooctene were examined. Other olefinic substrates were also used in this study and they exhibited good yields of the corresponding epoxides. This report shows the potential of using simple complexes or salts for the activation of hydrogen peroxide, owing to the interactions between the solvent medium and the active complex.

Thermal decomposition of branched silanes: a computational study on mechanisms.

The initial steps of the thermal decomposition of silanes in the gas phase were examined by DFT-B3LYP calculations, with particular attention being paid to the way in which the reactivity pattern changes with the degree of branching of the silane. Besides the established pathways-1,2-hydrogen shift, H(2) elimination, and homolytic dissociation-1,3-hydrogen shift was also explored as an initial reaction step which leads to disilene structures. Subsequent silylene insertion and initial steps of radical chain reactions were also studied. To estimate the energetic changes with temperature, various reaction free energies and the corresponding activation free energies up to 650 °C were calculated. Accordingly, the leading reaction channel at room temperature is 1,2-hydrogen shift with subsequent silylene insertion; for higher degrees of branching, competing pathways (homolytic dissociation, 1,3-hydrogen shift, and radical polymerization) gain in relative importance. At high temperatures, the rate-determining step changes to homolytic dissociation, and thereby the apparent rates of decomposition become dependent on the degree of branching.

Enantioselective total synthesis of the mexicanolides: khayasin, proceranolide, and mexicanolide.

The enantioselective total synthesis of the limonoids khayasin, proceranolide and mexicanolide was achieved via a convergent strategy utilizing a tactic aimed at incorporating natural products as advanced intermediates. This extended biomimetically inspired approach additionally achieved the enantioselective total synthesis of the intermediates azedaralide and cipadonoid B.

A combined DFT and NMR investigation of the zinc organometallic intermediate proposed in the syn-selective tandem chain extension-aldol reaction of ß-keto esters.

The tandem chain extension-aldol (TCA) reaction of ß-keto esters provides an α-substituted γ-keto ester with an average syn:anti selectivity of 10:1. It is proposed that the reaction proceeds via a carbon-zinc bound organometallic intermediate potentially bearing mechanistic similarity to the Reformatsky reaction. Evidence, derived from control Reformatsky reactions and a study of the structure of the TCA intermediate utilizing DFT methods and NMR spectroscopy, suggests the γ-keto group of the TCA intermediate plays a significant role in diastereoselectivity observed in this reaction. Such coordination effects have design implications for future zinc mediated reactions.

Metal-mediated reaction modeled on nature: the activation of isothiocyanates initiated by zinc thiolate complexes.

On the basis of detailed theoretical studies of the mode of action of carbonic anhydrase (CA) and models resembling only its reactive core, a complete computational pathway analysis of the reaction between several isothiocyanates and methyl mercaptan activated by a thiolate-bearing model complex [Zn(NH(3))(3)SMe](+) was performed at a high level of density functional theory (DFT). Furthermore, model reactions have been studied in the experiment using relatively stable zinc complexes and have been investigated by gas chromatography/mass spectrometry and Raman spectroscopy. The model complexes used in the experiment are based upon the well-known azamacrocyclic ligand family ([12]aneN(4), [14]aneN(4), i-[14]aneN(4), and [15]aneN(4)) and are commonly formulated as ([Zn([X]aneN(4))(SBn)]ClO(4). As predicted by our DFT calculations, all of these complexes are capable of insertion into the heterocumulene system. Raman spectroscopic investigations indicate that aryl-substituted isothiocyanates predominantly add to the C═N bond and that the size of the ring-shaped ligands of the zinc complex also has a very significant influence on the selectivity and on the reactivity as well. Unfortunately, the activated isothiocyanate is not able to add to the thiolate-corresponding mercaptan to invoke a CA analogous catalytic cycle. However, more reactive compounds such as methyl iodide can be incorporated. This work gives new insight into the mode of action and reaction path variants derived from the CA principles. Further, aspects of the reliability of DFT calculations concerning the prediction of the selectivity and reactivity are discussed. In addition, the presented synthetic pathways can offer a completely new access to a variety of dithiocarbamates.

A mechanistic investigation into the zinc carbenoid-mediated homologation reaction by DFT methods: is a classical donor-acceptor cyclopropane intermediate involved?

An extensive density functional theory (DFT, M05-2X) investigation has been performed on the zinc carbenoid-mediated homologation reaction of ß-keto esters. The mechanistic existence of a classical donor-acceptor cyclopropane intermediate was probed to test the traditional school of thought regarding these systems. Calculations of the carbenoid insertion step, following enolate formation, unmasked two possible pathways. Pathway B was shown to explain the proposed, but spectroscopically unobservable donor-acceptor cyclopropane intermediate, while the second (pathway A) reveals an alternative to the classical intermediate in that a cyclopropane transition state leads to product.

Allene as the parent substrate in zinc-mediated biomimetic hydration reactions of cumulenes.

The aim of our present investigation is to unravel the general mode of biomimetic activation of a wide variety of cumulenes by carbonic anhydrase (CA) models. Carbonic anhydrases allow the specific recognition, activation and transfer not only of CO2 but also of heteroallenes X=C=Y such as the polar or polarizable examples COS, CS2, H2CCO, and RNCS. Therefore, this enzyme class fulfils the requirements of excellent catalysts with a wide variety of important applications. Can this be extended to the isoelectronic but less reactive allene molecule, H2C=C=CH2 and extremely simplified models as mimetic concept for active center of the carbonic anhydrase? Allene is a waste product in the refinery, i.e. the C3-cut of the naphtha distillation; therefore, any addition product that can be obtained from allene in high yields will be of significant value. We investigated the complete catalytic cycle of a very simple model reaction, the hydration of allene, using density functional theory. Additionally, calculations were performed for the uncatalyzed reaction. There are two possible ways for the nucleophilic attack leading to different products. The zinc hydroxide complex and the water molecule can react at the central or the terminal carbon atoms (positional selectivity), the resulting products are 2-propen-1-ol and propen-2-ol, respectively, acetone. The calculations indicate a significant lower energy barrier for the rate determining step of the formation of propen-2-ol and therefore a well-expressed regioselectivity for the addition of such small molecules. The zinc complex has a pronounced catalytic effect and lowers the activation barrier from 262.5 to 123.9 kJ/mol compared with the uncatalyzed reaction. This work suggests the most probable paths for this reaction and discloses the necessity for the development of novel catalysts.

Mechanistic aspects of the lycopodine Michael-Claisen domino cyclization.

The Michael-Claisen domino (MCD) cyclization used in the lycopodine synthesis by Stork, was evaluated mechanistically using DFT calculations. Calculations suggest that a dianion is not formed, which conforms to classical dianion formation normally requiring strong kinetic bases. Instead ethoxide in ethanol produces a monoanionic species driving the MCD cyclization. This endeavor has opened up potential to expand the scope of this unique reaction and provide educational clarity.

Carbon dioxide insertion into diamines: a computational study of solvent effects.

We studied computationally, on the model compound ethylenediamine, the insertion of carbon dioxide into diamines, yielding cyclic urea compounds. Two mechanisms were elaborated, depending on the value of the dielectric constant (DC) of the solvent. Accordingly, reaction mixtures with a high DC lead to carbamates, whereas lower DC values result in the preferred product cyclic urea. Additives behaving as "proton shuttles" act as catalysts, significantly reducing the activation barriers of insertion and ring closure to surmountable values. CO(2) insertion into diamines may also occur by autocatalysis, even without further additives, but under less favorable conditions, for example, lower yields. Amine reagents are most efficient at proton shuttling, followed by alcohols. The activation barrier of the rate-limiting step is lowered in a reaction mixture with higher values of DC, up to a critical value ε(cr) ≈ 18. Hence, in a suitably optimized reaction mixture, ring closure is suggested to occur under milder conditions than those previously applied experimentally. The two roles of the additive, that is, acting as proton shuttling agent and adjusting the effective DC of the reaction mixture, do not have to be assigned to a single compound, possibly affording a handle on process optimization.

The zinc complex catalyzed hydration of alkyl isothiocyanates.

Based upon our preceding studies of the hydration of CO(2), COS and CS(2), accelerated by the carbonic anhydrase (CA) using simplified [ZnL(3)OH](+) complexes as model catalysts, we calculated the hydration mechanisms of both the uncatalyzed and the [ZnL(3)OH](+)-catalyzed reactions (L = NH(3)) of isothiocyanates RNCS on the B3LYP/6-311+G(d,p) level of theory. Interestingly, the transition state for the favored metal mediated reaction with the lowest Gibbs free energy is only slightly higher than in the case of CO(2) (depending on the attacking atom (N or S). Calculations under inclusion of solvent corrections show a reduction of the selectivity and a slight decrease of the Gibbs free energy in the rate-determining steps. The most plausible pathway prefers the mechanism via a Lindskog proton-shift transition state leading to the thermodynamically most stable product, the carbamatic-S-acid. Furthermore, powerful electron withdrawing substituents R of the cumulenic substrates influence the selectivity of the reaction to a significant extent. Especially the CF(3)-group in trifluoromethylisothiocyanate reverses the selectivity. This investigation demonstrates that reaction principles developed by nature can be translated to develop efficient catalytic methods, in this case presumably for the transformation of a wide variety of heterocumulenes aside from CO(2), COS and CS(2).