ETC: A Mechanistic Concept for Inorganic and Organic Chemistry

The concept of electron transfer catalysis (ETC), or more specifically “Double Activation Induced by Single Electron Transfer” (DAISET) gives an opportunity to connect experimental facts never previously correlated. The first activation results from the transfer of an electron to (or from) a molecular species; the second activation results from the build-up of a reaction chain able to reproduce the species formed in the first step. The starting point of this review is the S_RN 1 mechanism where principle and experimental diagnostic criteria are critically discussed. The thermal and photochemical exchange and substitution reactions of Pt^IV complexes are then reviewed together with the exchange reaction [AuCl₄]^?/Cl^?, reactions with Grignard reagents and other organometallic reagents, as well as the redox behavior of electronically excited organic compounds. Photochemical applications, including solar energy conversion are discussed. New aspects are also presented for the mechanistic problem “S_N 2 reaction or SET process?” Moreover, the concept has significance for S_H2 reactions at metal centers, molecule-induced homolyses, reactions of complexes, as well as electrochemical processes.–Unless otherwise specified, only double activation (DAISET) processes will be discussed in this article.     

Dye-sensitized photooxygenation of sugar furans: novel bis-epoxide and spirocyclic C-nucleosides

Dye-sensitized photooxygenation of 2-methyl 5-(2,3,5-tri-O-acetyl-β-d-ribofuranosyl)furoate leads to (1S,4R)-endo-peroxide, highlighting a high facial diastereoselectivity. This endo-peroxide rearranges into syn-(1R,2R:3S,4R)-diepoxide C-nucleoside, while by Et₂S-reduction followed by NEt₃ catalysis affords a spirocyclic C-nucleoside.     

Reactions of urocanic acid (UCA) methyl esters with singlet oxygen and 4-methyl-1,2,4-triazoline-3,5-dione (MTAD)

Singlet oxygen adds to the imidazole ring of cis- and trans-methyl urocanate (MUC) to yield the corresponding 2,5-endoperoxides, which are modestly stable at low temperature but decompose upon warming to form complex reaction mixtures. MTAD, a singlet oxygen mimic, reacts with cis- and trans-MUC to yield stereospecific [4+2] reaction products involving the olefinic side chain and the C₄-C₅ double bond of the imidazole ring. trans-MUC forms a 1:2 MTAD adduct while the cis isomer yields only the 1:1 adduct at 25 °C. The stereospecificity and absence of MeOH trapping adducts indicate that these reactions may not involve open or trappable dipolar intermediates.     

Regioselectivity in the ene-reaction of singlet oxygen with cyclic alkenes: photooxygenation of methyl-substituted 1,4-cyclohexadiene derivatives

The photooxygenation of the 1-methyl-, 2,3-dimethyl-, and 1,4-dimethylcyclohexa-1,4-dienes, which are readily available through Birch reduction, yielded the corresponding ene-products. The formed endocyclic dienes were trapped by the addition of singlet oxygen to give the corresponding bicyclic endoperoxy hydroperoxides. In the case of 1-methylcyclohexa-1,4-diene and 1,4-dimethylcyclohexa-1,4,-diene, the cis-effect determined the product distribution. Photooxygenation of 2,3-dimethylcyclohexa-1,4-dienes gave mainly exocyclic olefin, which was attributed to the lowered rotational barrier of the methyl group and increased reactivity of the methyl groups.     

Mechanistic Aspects of Olefin Metathesis

In this paper views regarding the nature of the transition state in olefin metathesis are discussed. Earlier concepts that assumed a pairwise scrambling mechanism have been recently challenged. Metathesis studies involving acyclic as well as cyclic olefins have been reported which strongly suggest a chain process that may involve a carbene-to-metallocycle interconversion as the pathway responsible for transalkylidenation. Catalytic systems that display a low apparent metathesis activity on terminal olefins display a unique specificity in cross reactions with internal olefins. Critical experiments indicate that terminal olefins rapidly undergo regenerative metathesis preferentially. Results suggest that in the transient metallocycle, the most stringent steric requirements occur at the β-carbon, although the origin of this steric demand is not obvious.     

Mechanistic Organic Photochemistry

Organic photochemical reactions can be understood as transformations of the electronically excited states of the reactant molecules. By considering Lewis structure or molecular orbital representations of these excited states it is possible to outline the several possible reactions available in the case of a given reactant. A number of different types of photochemical transformations are now reasonably well understood. In these cases one finds the same common controlling feature, namely the tendency for an excited state species to follow mechanistic pathways of minimum energy and the requirement for continuous electron redistribution in following these pathways. These preferred transformations can often be selected by inspection of relative bond orders for different types of bonding, by comparison of the potential energy surfaces available to the excited state molecules, and by use of correlation diagrams. The reactions derive from both singlet and triplet states, and one of the more reliable methods now available for identifying excited states reacting is termed the “fingerprint method”. Examples of the author's mechanistic approach are given both for ketone and for hydrocarbon photochemistry.     

Spiroketals of monosaccharides by dye-sensitized photooxygenation of furyl ketoses

[4+2] Cycloaddition of singlet oxygen to suitably substituted furans followed by reduction of the corresponding endoperoxides afforded functionalized enediones which quickly cyclized into the titled spiroketals. The reported method represents a green synthetic one-pot procedure for novel [6,6]-, [5,6]-, and [5,5]-spiroketals of sugars.     

Synthesis and Photooxygenation of Linear and Angular Furocoumarin Derivatives as a Hydroxyl Radical Source: Psoralen,Pseudopsoralen, Isopseudopsoralen,and Allopsoralen

Synthesis of linear and angular furocoumarins with new skeleton structure of potential photobiological feature interest was carried out through Williamson reaction of hydroxycoumarins with 3‐chloro‐2‐butanone followed by cyclization with polyphosphoric acid or by heating in a strongly alkaline solution. The photooxygenation reactions of synthesized furocoumarins were performed in chloroform and in the presence of tetraphenylporphyrin as singlet oxygen sensitizer (¹O₂). The photooxygenation reactions afforded the photocleaved product through [2 + 2] cycloaddition and the photooxygenated products through ene reaction and [4 + 2] cycloaddition. The photoproducts were isolated and fully characterized by spectral analyses.     

Chemistry of singlet oxygen with arylphosphines

The chemistry of singlet oxygen with a variety of arylphosphines has been studied. Rates of singlet oxygen removal by para-substituted arylphosphines show good correlation with the Hammett σ parameter (ρ=−1.53 in CDCl₃), and with the Tolman electronic parameter. The only products for the reactions of these phosphines with singlet oxygen are the corresponding phosphine oxides. Conversely, for ortho-substituted phosphines with electron-donating substituents, there are two products, namely a phosphinate formed by intramolecular insertion and phosphine oxide. Kinetic analyses demonstrate that both products are formed from the same intermediate, and this allows determination of the rate ratios for the competing pathways. Increasing the steric bulk of the phosphine leads to an increase in the amount of insertion product. VT NMR experiments show that peroxidic intermediates can only be detected for very hindered and very electron-rich arylphosphines.     

Electron Transfer Reactions in Chemistry: Theory and Experiment (Nobel Lecture)

Since the late 1940s, the field of electron transfer processes has grown enormously, both in chemistry and biology. The development of the field, experimentally and theoretically, as well as its relation to the study of other kinds of chemical reactions, presents to us an intriguing history, one in which many threads have been brought together. In this lecture, some history, recent trends, and my own involvement in this research are described.     

Kinetic Evidence for Reactive Intermediates

Spectroscopic methods have recently been developed that allow the direct detection of reactive intermediates under favorable circumstances. The most general and reliable method, however, is still the indirect one, which makes use of the priciple of kinetic competition; this method is based on the freedom of the intermediate to choose between several reaction possibilities. The following discussion is addressed less to the specialist in reaction mechanisms than to the outsider who wishes to obtain some idea of the value and limitations of the kinetic method.     

Chemistry of dioxine-annelated cycloheptatriene endoperoxides and their conversion into tropolone derivatives: an unusual non-benzenoid singlet oxygen source

The chemistry of two bicyclic endoperoxides, obtained by photooxygenation of 2,3-dihydro-7H-cyclohepta[1,4]dioxine and 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one was investigated with the aim of synthesizing the respective tropolone derivatives. The reaction of these endoperoxides with base, thiourea and their thermolysis provided the desired tropolone derivatives in high yield. On the other hand, the thermolysis of the endoperoxide derived from 2,3-dihydro-7H-cyclohepta[b][1,4]dioxin-7-one underwent an unprecedented route and formed parent molecule and singlet oxygen instead of the expected troponoids. The formation mechanisms of all products are discussed.     

Mechanistic Analysis of Solution Reactions by Non-Isothermal Calorimetry

For the rapid kinetic and energetic analysis of reactions in solution (τ_20°C > 10^-4s) by differential thermal analysis (DTA), the following thermogram parameters are defined as characterizing the start of the reaction: 1. initial temperature, 2. activation energy of the initiation reaction. In conjunction with the shape index (asymmetry of the DTA curve) and the half width of the DTA curve referred to standard physical conditions (cell constant, heating rate, and temperature difference), these quantities allow a simple distinction between one-step reactions of first and second order and composite reactions. It is possible to recognize whether a process involves parallel, successive, or equilibrium reactions, or combinations of these. The reaction mechanism can be clarified in many cases by measurements at various concentrations and heating rates and by discussion of the enthalpy values. The shortened method described in this report for the evaluation of the thermograms was derived with the aid of an analog computer and checked experimentally.     

Photooxygenation of 3-aryl-2-cyclohexenols: synthesis of a new series of antimalarial 1,2,4-trioxanes

Using easily accessible 3-aryl-2-cyclohexenols, a photooxygenation route for the preparation of bicyclic 1,2,4-trioxanes is reported. Several of these trioxanes have shown significant antimalarial activity against multidrug resistant Plasmodium yoelii in mice by the oral route.     

Computer-Assisted Solution of Chemical Problems—The Historical Development and the Present State of the Art of a New Discipline of Chemistry

The topic of this article is the development and the present state of the art of computer chemistry, the computer-assisted solution of chemical problems. Initially the problems in computer chemistry were confined to structure elucidation on the basis of spectroscopic data, then programs for synthesis design based on libraries of reaction data for relatively narrow classes of target compounds were developed, and now computer programs for the solution of a great variety of chemical problems are available or are under development. Previously it was an achievement when any solution of a chemical problem could be generated by computer assistance. Today, the main task is the efficient, transparent, and non-arbitrary selection of meaningful results from the immense set of potential solutions—that also may contain innovative proposals. Chemistry has two aspects, constitutional chemistry and stereochemistry, which are interrelated, but still require different approaches. As a result, about twenty years ago, an algebraic model of the logical structure of chemistry was presented that consisted of two parts: the constitution-oriented algebra of be- and r-matrices, and the theory of the stereochemistry of the chemical identity group. New chemical definitions, concepts, and perspectives are characteristic of this logic-oriented model, as well as the direct mathematical representation of chemical processes. This model enables the implementation of formal reaction generators that can produce conceivable solutions to chemical problems—including unprecedented solutions—without detailed empirical chemical information. New formal selection procedures for computer-generated chemical information are also possible through the above model. It is expedient to combine these with interactive methods of selection. In this review, the Munich project is presented and discussed in detail. It encompasses the further development and implementation of the mathematical model of the logical structure of chemistry as well as the experimental verification of the computer-generated results. The article concludes with a review of new reactions, reagents, and reaction mechanisms that have been found with the PC-programs IGOR and RAIN.     

Mechanistic study of multi-step nucleophilic substitution for trifluoromethylated styrenes

The key steps of the reactions of nitrogen nucleophiles with β-halogen-β-trifluoromethylstyrenes have been studied by ¹⁹F and ¹H NMR monitoring and quantum-chemical calculations. In contrast to the mechanism proposed earlier for nucleophilic vinylic substitution of captodative carbonyl-bearing haloalkenes, this reaction proceeds via either E–Ad or Ad–E sequence depending on the nature of aromatic substituents of the parent styrenes.     

Phosphonio‐benzophospholide Zwitterions as Bridging 8e‐Donor Ligands: Synthetic and Mechanistic Studies

Reactions of the phosphonio‐benzophospholide π‐complexes 3a, b[Cr] with [M(CO)₅(olefin)] or of the σ‐complexes 2a, b[M] (M = Cr, Mo, W) with [M(CO)₃(aren)] lead to the first binuclear complexes 4a, b[CrM] featuring phosphonoio‐benzophospholides as μ‐bridging 8e‐donor ligands to two group 6 metal atoms. The constitution of the products was determined by spectroscopic and X‐ray diffraction studies. Mixed complexes with both group 6 and 7 metals were not accessible. Mechanistic studies showed that the reactions follow a complicated mechanism whose single steps may involve transfer of either M(CO)_n fragments or single CO ligands between complexes; the latter are associated with a σ/π‐coordination isomerization of the benzophospholide unit. Competition between both reaction channels can lead to the formation of product mixtures whose composition is controlled by the relative thermodynamic stabilities of the products. Computational studies suggest that in the more stable isomer of heterobimetallic complexes 4a, b[MM′] end‐on coordination to the heavier and side‐on coordination to the lighter metal atom is preferred.     

The Elucidation of Peroxyl Radical Reactions in Aqueous Solution with the Help of Radiation-Chemical Methods

Whenever free radicals are formed, independent of whether this occurs thermally, is induced by UV or ionizing irradiation, or takes place in redox reactions, they are converted rapidly into the corresponding peroxyl radicals in the presence of oxygen. Peroxyl radical reactions in aqueous environments are observed not only in aquatic systems (e.g., rivers, lakes and oceans) but also in the living cell and to a considerable degree even in the atmosphere (in water droplets). The peroxyl radical chemistry occurring in this medium is often very different from that observed in the gas phase or in organic solvents. In spite of the great importance of these reactions in medicine (for example in anti-cancer irradiation therapy and ischaemia) there have been comparatively few studies of peroxyl reactions in aqueous media. Radiation-chemical techniques such as pulse radiolysis offer the best means for carrying out such studies, so that it is not surprising that the majority of the information available in this area has been obtained with the help of radiation-chemical methods. The radiation chemistry of water can be con trolled in such a manner that the main products are ^˙OH radicals (90 % yield), which react with substrate molecules to give substrate radicals and in the presence of oxygen to give substrate peroxyl radicals. The experimental conditions can also be varied in such a way that HO/O radicals can be formed in 100 % yield and caused to react with substrates. We therefore have a simple access to these intermediates, which are extremely important in biological systems. A detailed product analysis, supported by kinetic studies carried out with the help of pulse radiolysis, has been used to clarify the chemistry of a series of peroxyl radicals, so that sufficient material is now available to justify a review of the variety of the peroxyl radical reactions studied by means of radiation-chemical methods. A more general survey of the physical properties of the peroxyl radicals and their unimolecular and bimolecular reactions will be followed by a discussion of selected examples of various classes of substance. Because of the great biological importance of radical-induced DNA damage this area will also be treated briefly.     

Mechanistic Insight into Hydroboration of Imines from Combined Computational and Experimental Studies

Boron Lewis acid-catalyzed and catalyst-free hydroboration reactions of imines are attractive due to the mild reaction conditions. In this work, the mechanistic details of the hydroboration reactions of two different kinds of imines with pinacolborane (HBpin) are investigated by combining density functional theory calculations and some experimental studies. For the hydroboration reaction of N-(α-methylbenzylidene)aniline catalyzed by tris[3,5-bis(trifluoromethyl)phenyl]borane (BAr^F₃), our calculations show that the reaction proceeds through a boron Lewis acid-promoted hydride transfer mechanism rather than the classical Lewis acid activation mechanism. For the catalyst- and solvent-free hydroboration reaction of imine, N-benzylideneaniline, our calculations and experimental studies indicate that this reaction is difficult to occur under the reaction conditions reported previously. With a combination of computational and experimental studies, we have established that the commercially available BH₃ ⋅ SMe₂ can serve as an efficient catalyst for the hydroboration reactions of N-benzylideneaniline and similar imines. The hydroboration reactions catalyzed by BH₃ ⋅ SMe₂ are most likely to proceed through a hydroboration/B−H/B−N σ-bond metathesis pathway, which is very different from that of the reaction catalyzed by BAr^F₃.