Abstract: 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a highly effective reagent for promoting C–H bond functionalization. The oxidative cleavage of benzylic and allylic C–H bonds using DDQ can be coupled with an intra- or intermolecular nucleophilic addition to generate new carbon–carbon or carbon–heteroatom bonds in a wide range of substrates. The factors that control the reactivity of these reactions are well-defined experimentally, but the mechanistic details and the role of substituents in promoting the transformations have not been firmly established. Herein, we report a detailed computational study on the mechanism and substituent effects for DDQ-mediated oxidative C–H cleavage reactions in a variety of substrates. DFT calculations show that these reactions proceed through a hydride transfer within a charge transfer complex. Reactivity is dictated by the stability of the carbocation intermediate, the degree of charge transfer in the transition states, and, in certain cases, secondary orbital interacti...

Abstract: Silylium ions facilitate the catalytic direct cross-coupling of aryl fluorides with simple arenes and alkanes. This C–H arylation approach is initiated by silylium ion-mediated fluoride abstraction, followed by Friedel–Crafts or C–H insertion reactions of the resulting phenyl cation equivalents. An ortho-silyl group in the fluoroarene substrate is the key for selective intermolecular transformations, stabilizing the aryl cation intermediate and serving as an internal silylium ion precursor.

Abstract: Carbocation/polyol systems are shown to be highly efficient catalysts for the synthesis of cyclic carbonates from epoxides and carbon dioxide at 50 °C and 5 MPa CO2 pressure. The best activity was shown by the combination of crystal violet and 1,1′-bi-2-naphthol (BINOL), which could be recycled five times with no loss of activity. The presence of specific interactions between the amino groups of the carbocation and the hydroxyl protons was confirmed by NMR experiments. The Job plots for the crystal violet iodide/BINOL and brilliant green iodide/BINOL systems showed that the catalytic systems consist of one molecule of the carbocation and one molecule of BINOL. Mechanistic studies using a deuterated epoxide indicate that there was some loss of epoxide stereochemistry during the reaction, but predominant retention of stereochemistry is observed. On this basis, a catalytic cycle is proposed.

Abstract: Graphene oxide (GO) and carboxylic acid-functionalized GO (GO-CO2H) have been found to efficiently promote the heterogeneous and environmentally friendly pinacol rearrangement of 1,2-diols and the direct nucleophilic substitution of allylic alcohols. In general, high yields and regioselectivities are obtained in both reactions using 20 wt% of catalyst loading and mild reaction conditions.

Abstract: We recently reported that carboxylic acids can be oxidized to lactone products by potassium persulfate and catalytic copper acetate. Here, we unravel the mechanism for this C-H functionalization reaction using desorption electrospray ionization, online electrospray ionization, and tandem mass spectrometry. Our findings suggest that electron transfer from a transient benzylic radical intermediate reduces Cu(ii) to Cu(i), which is then re-oxidized to Cu(ii) in the catalytic cycle. The resulting benzylic carbocation is trapped by the pendant carboxylate group to give the lactone product. Formation of the putative benzylic carbocation is supported by Hammett analysis. The proposed mechanism for this copper-catalyzed oxidative cyclization process differs from earlier reports of analogous reactions, which posit a substrate carboxylate radical as the reactive oxidant.

Abstract: The mechanism of the rearrangement of oxiranyl N-methyliminodiacetyl (MIDA) boronates in dicholoromethane has been extensively investigated with density functional theory. Several reaction pathways were examined. Our results revealed that the most-favorable mechanisms for the BF3-promoted rearrangement of 2-phenyl oxiranyl MIDA boronate (1) and 1-phenyl oxiranyl MIDA boronate (24) comprise two steps: ring opening of the epoxide to a carbocation intermediate followed by migration of a MIDA-boryl group (for the reaction of 1) and hydrogen (for the reaction of 24), to give the same BF3-coordinated α-boryl aldehyde in both cases. The first step of the ring opening of the epoxide is the rate-determining step of these reactions. In the rearrangement step for the reaction of 1, the MIDA-boryl group migrates easily, probably because of its electron-rich sp3-hybridized boron center. For 24, the most-favorable pathway involves a rare boryl-substituted carbocation. The course of these reactions is mainly controlled ...

Abstract: The first asymmetric synthesis of ent-fragransin C1 was reported. The key step involves an intramolecular C–O bond formation (furan ring formation) via chemoselective generation of the benzylic carbocation leading to the 2,3-anti-3,4-syn-4,5-anti-tetrahydrofuran moiety as a single diastereomer in good yield. Our synthesis confirms that ent-fragransin C1 possesses 2R,3R,4S,5S configurations.

Abstract: A series of 9-fluorenyl cations has been studied and it is shown that increasing charge on a heterocyclic substituent group enhances the anti-aromatic character of the carbocation system. Similarly, a series of dibenzosuberenyl cations has been studied and increasing charge on a substituent group is shown to enhance aromatic character in the carbocation system. These studies include the direct observations of dicationic and tricationic species using stable-ion conditions and low temperature NMR. The structures of these ions were further characterized using DFT calculations, confirming that highly charged organic ions may exhibit unusual distributions of π-electrons and delocalization of electrons in 4n or 4n+2 π-systems.

Abstract: A unique tandem reaction of sequence-controlled cationic copolymerization and site-specific hetero-Diels–Alder (DA) reaction is demonstrated In the controlled cationic copolymerization of furfural and 2-acetoxyethyl vinyl ether (AcOVE), only the furan ring adjacent to the propagating carbocation underwent the hetero-DA reaction with the aldehyde moiety of another furfural molecule A further and equally important feature of the copolymerization is that the obtained copolymers had unprecedented 2:(1 + 1)-type alternating structures of repeating sequences of two VE and one furfural units in the main chain and one furfural unit in the side chain The specific DA reaction is attributed to the delocalization of the positive charge to the side furan ring

Abstract: Cationic terpolymerization of an alkyl vinyl ether (VE) with oxetane and methyl ethyl ketone (MEK) proceeded via concurrent vinyl-addition, ring-opening, and carbonyl-addition mechanisms. Highly selective crossover reactions occurred in a one-way cycle, resulting in the generation of multiblock polymers with constitutional repeating units comprising a poly(VE) block, a polyoxetane block, and a single MEK unit. The ketone efficiently functioned as a non-homopolymerizable monomer, which reacted with the oxetane-derived oxonium ion to generate an alkoxy group-adjacent carbocation or an oxocarbenium ion. Furthermore, the resulting carbocation allowed to react with only VEs. The polymerization, which was induced with an initiating system of Ph3C+PF6–, 2,6-di-tert-butylpyridine, and 1,4-dioxane, was partly mediated by long-lived propagating species. NMR analysis of the chain end structures revealed that mono- and difluorophosphate moieties generated via the hydrolysis of PF6– were partially responsible for the ...

Abstract: A novel metal- and acid-free preparation of synthetically useful α,β-unsaturated carbonyl compounds from propargyl alcohols has been realized. This Meyer–Schuster rearrangement process is effectively catalyzed by methyl triflate (20 mol%) to prepare a broad scope of conjugated E -enals and E -enones generally in good to excellent yields (up to 90%). This reaction procedure operates under mild conditions (70 °C), in air, with short reaction times (1 h). Moreover, a carbocation intermediate trapped by the solvent 2,2,2-trifluoroethanol was isolated during this transformation.

Abstract: Chloronium cations in their salts (CnH2n+1)2Cl+{CHB11Cl11–}, with n = 1 to 3 and exceptionally stable carborane anions, are stable at ambient and elevated temperatures. The temperature at which they decompose to carbocations with HCl elimination (below 150 °C) decreases with the increasing n from 1 to 3 because of increasing ionicity of C–Cl bonds in the C–Cl+–C bridge. At room temperature, the salts of cations with n ≥ 4 [starting from t-Bu2Cl+ or (cyclo-C5H11)2Cl+] are unstable and decompose. With decreasing chloronium ion stability, their ability to interact with chloroalkanes to form oligomeric cations increases. It was shown indirectly that unstable salt of fluoronium ions (CH3)2F+(CHB11F11–) must exist at low temperatures. The proposed (CH3)2F+ cation is much more reactive than the corresponding chloronium, showing at room temperature chemical properties expected of (CH3)2Cl+ at elevated temperatures.

Abstract: Comparison of experimental infrared (IR) spectra of the simplest carbocations (with the weakest carborane counterions in terms of basicity, CHB11Hal11-, Hal = F, Cl) with their calculated IR spectra revealed that they are completely inconsistent, as previously reported for the t-Bu+ cation [Stoyanov E. S., et al. J. Phys. Chem. A, 2015, 119, 8619]. This means that the generally accepted explanation of hyperconjugative stabilization of the carbocations should be revised. According to the theory, one CH bond (denoted as ) from each CH3/CH2 group transfers its σ-electron density to the empty 2pz orbital of the sp2 C atom, whereas the σ-electron density on the other CH bonds of the CH3/CH2 group slightly increases. From experimental IR spectra it follows that donation of the σ-electrons from the bond to the 2pz C-orbital is accompanied by equal withdrawal of the electron density from other CH bonds, that is, the electrons are supplied from each CH bond of the CH3/CH2 group. As a result, all CH stretches of the group are red shifted, and IR spectra show typical CH3/CH2 group vibrations. Experimental findings provided another clue to the electron distribution in the hydrocarbon cations and showed that the standard computational techniques do not allow researchers to explain a number of recently established features of the molecular state of hydrocarbon cations.

Abstract: Chorismatase is an important enzyme involved in Shikimate pathway, which catalyzes the conversion of chorismate into pyruvate and (dihydro)-benzoic acid derivatives. According to the outcomes of catalytic reactions, chorismatases can be divided into three subfamilies: CH-Fkbo, CH-Hyg5 and CH-XanB2. Recently, the crystal structures of CH-Fkbo and CH-Hyg5 from Streptomyces hygroscopicus have been successfully obtained, allowing us to perform QM/MM calculations to explore the reaction details. Our calculation results support the proposal that CH-Fkbo and CH-Hyg5 employ different catalytic mechanisms and gave the mechanistic details. Fkbo follows a typical hydrolytic mechanism, which contains three consecutive steps, including the protonation step of the methylene group of substrate, the nucleophilic attack of the resulted carbocation by activated water and cleavage of C2'-O8 bond of tetrahedral intermediate (hemiketal). The protonation of methylene group and the C2'-O8 cleavage correspond to similar energy barriers (26.5 and 24.8 kcal/mol), suggesting both steps to be rate-limiting. Whereas Hyg5 employs an intramolecular mechanism, in which the oxygen from C4 migrates to C3 via an arene oxide intermediate. The first step of Hyg5, which corresponds to the concerted protonation of methylene group and the cleavage of C3-O8, is calculated to be rate-limiting with an energy barrier of 26.3 kcal/mol. The nonconserved active site residue G240Hyg5 (or A244Fkb °) is suggested to be responsible for leading to different reaction mechanism in CH-Fkbo and CH-Hyg5. During the catalytic reaction, residue C327 plays an important role in directing the product selectivity in Hyg5 enzyme. Proteins 2017; 85:1146-1158. © 2017 Wiley Periodicals, Inc.

Abstract: Group 4 metallocene-mediated cationic ring-opening polymerizations of a series of lactones and cyclic carbonates, with different ring sizes (n=4–8) have been theoretically studied. Using the “naked cation” approach in combination with density functional theory, the activated chain-end mechanism and the influence of transition metals, solvent and monomer ring size on the polymerizability were explored in detail. The results showed that the cationic metallocene–monomer complex, [catalyst][monomer]+, is formed, generating cationic (carbocation ion) species responsible for polymer chain growth. We found that poor polymerizability of five-membered lactone and six-membered ring carbonate depends not only on the nature of the monomer ring size but also the relative stability of the complex, which was found to correlate well with the ring strain. Subsequently, several propagation steps take place through an SN2 reaction which involves ring opening of an active monomer, via alkyl–oxygen bond cleavage. Based on the...

Abstract: A detailed mechanistic investigation identified the stepwise nature of the 1,3-aryl shift, which enables our recently disclosed Al3+ -catalyzed insertion of unactivated alkynes into the sp2 -sp3 C-C bond of benzyl alcohols. The selectivity for the rearranged product was found to be induced by the continued coordination of the aluminum catalyst to the rearranging species, which is encouraged by a reversible background reaction. This participation of the catalyst beyond the ionization step is unique in the realm of carbocation driven reactions and opens up the possibility of a catalyst-induced chiral induction in the future. Furthermore, the study represents a rare example of detailed mechanistic analysis of a reaction with a product selectivity that changes with increasing conversion.

Abstract: The carbocation CH5 + has a unique structure of C s symmetry with three 2-center-2-electron bonds and one 3-center-2-electron bond. This ground-state geometry is different from the prediction by the VSEPR model. We have investigated this carbocation along with related systems, among them, BH5, BLi5, CLi5 +, NH5 2+, NLi5 2+, to seek possible trends and regularities in the variations of their ground-state geometries.

Abstract: The electrophilic addition of a hydrohalic acid (HX) to an alkene is often one of the first reactions learned in second-year undergraduate organic chemistry classes. During the ensuing discussion of the mechanism, it is shown that this reaction follows Markovnikov’s rule, which states that the hydrogen atom will attach to the carbon with fewer substituents while the halogen atom will attach to the carbon with more substituents. However, in the preparation of tropic acid, the reaction of HCl with atropic acid (2-phenylpropenoic acid) does not follow this rule because it is a conjugated system. Molecular modeling of the possible carbocation intermediates suggests that the reaction follows a conjugate addition mechanism involving a 1,4-addition of HCl across the conjugated alkene and carboxyl group rather than addition across the alkene as students often first propose. PM3 semiempirical calculations are used to determine the energies of three possible carbocation intermediates. The energies obtained from the...

Abstract: The methyl carbocation is ubiquitous in gaseous environments, such as planetary ionospheres, cometary comae, and the interstellar medium, as well as combustion systems and plasma setups for technological applications. Here we report on a joint experimental and theoretical study on the mechanism of the reaction CH3+ + CH3CCCH3 (but-2-yne, also known as dimethylacetylene), by combining guided ion beam mass spectrometry experiments with ab initio calculations of the potential energy hypersurface. Such a reaction is relevant in understanding the chemical evolution of Saturn’s largest satellite, Titan. Two complementary setups have been used: in one case, methyl cations are generated via electron ionization, while in the other case, direct vacuum ultraviolet photoionization with synchrotron radiation of methyl radicals is used to study internal energy effects on the reactivity. Absolute reactive cross sections have been measured as a function of collision energy, and product branching ratios have been derived....

Abstract: Cyclopropyl-cyclopropyl rearrangement can be achieved selectively by intramolecular trapping of cyclopropylmethyl carbenium ions with an internal nucleophile. This can be exploited as a useful method for the introduction of a cyclopropyl group into complex molecules using readily accessible disubstituted cyclopropane intermediates.

Abstract: A series of SN 1-type reactions has been studied under various conditions to clarify the role of supercritical carbon dioxide (scCO2 ) as reaction medium for this kind of transformations. The application of scCO2 did not result in higher yields in any of the experiments in comparison to those under neat conditions or in the presence of other inert compressed gases. High-pressure UV/Vis spectroscopic measurements were carried out to quantify the degree of carbocation formation of a highly SN 1-active alkyl halide as a function of the applied solvent. No measureable concentration of carbocations could be detected in scCO2 , just like in other low polarity solvents. Taken together, these results do not support the previously claimed activating effect via enhanced SN 1 ionization due to the quadrupolar moment of the supercritical fluid.

Abstract: Styrene derivatives can form carbocation species upon contact with zeolites. In this study, structures of a series of styrene derivatives with substituents in the para position, which have been obtained experimentally, were elucidated using theoretical calculations. Styrene with F, Cl, Br, methyl (Me) and methoxy (MeO) groups was studied by means of (TD)-DFT calculations. Electronic structure changes depending on the substituents, Br and MeO, showed smaller HOMO–LUMO gaps in the series. Theoretical excitation energies of two dimeric species were found to match very well with absorption bands reported experimentally. Ternary and secondary carbocation dimeric species were found to be responsible for the absorption of light in the visible region. Both structures were studied using aromaticity indexes as well as atoms-in-molecules theory to understand the changes in electron delocalization to produce non-typical light absorbing compounds. Aromatic rings with all the substituents lose aromaticity to reinforce charge transfer within the molecule, stabilizing the adjacent carbocation species. The results are attractive to interpret the electronic spectra of such compounds formed within zeolites and for a better understanding of the electronic structure as well as the reaction mechanisms of the carbocation species.

Abstract: 1 H and 13 C NMR were recorded on a JEOL JNM-ECP500 spectrometer (500 MHz for 1 H NMR, 126 MHz for 13 C NMR). Chemical shifts are reported as δ values in ppm and calibrated by residual solvent peak (CDCl3, δ 7.26 for 1H NMR, δ 77.00 for 13 C NMR; CD3OD, δ 3.31 for 1 H NMR, δ 49.00 for 13 C NMR; CD2Cl2, δ 5.32 for 1 H NMR, δ 53.8 for 13 C NMR) or tetramethylsilane (δ 0 for 1 H NMR). Abbreviations are following: s (singlet), d (doublet), t (triplet), q (quartet), br (broad peak), m (complex multiplet). Inflared spectra were measured on a JASCO FT/IR-4200 spectrometer. Mass spectra were recorded on a JEOL JMS-700 MStaion [EI (70 eV), CI, FAB and ESI]. Flush column chromatography was performed by MERCK Silica gel 60. The progress of reactions was monitored by silica gel thin layer chromatographyplates (MERCKTLC Silicagel 60 F254). Phosphomolybdic acid ethanol solution, ninhydrin-acetic acid butanol solution and anisaldehyde-acetic acid-sulfuric acid ethanol solution were used as TLC stain. All reagents were purchased from Sigma-Aldrich, Wako pure chemical industries, Ltd, TCI (Tokyo Chemical Industry, Co. Ltd), Kanto Chemical Co. Inc., and Nakalai Tesque. Used Dehydrated solvents —tetrahydrofuran, dichloromethane and toluene— were purchased from Kanto Chemical, Wako pure chemical industries, Ltd, and Nakalai Tesque. Sodium azide purchased from Nakalai Tesque was carefully handled, and transferred with plastic spatulas.