The polymerization of 3-chloro-1-propyne and 3-bromo-1-propyne with Mocl5 and WCL6 based initiators and the structure of the resulting polymers

The WCl₆ and MoCl₅ initiated polymerizations of 3-chloro-1-propyne and 3-bromo-1-propyne were performed in both halogenated and aliphatic non-nucleophilic and in aromatic nucleophilic solvents. The structure of the obtained polymers suggested that the polymerization reaction occurs in two steps. In both nucleophilic and non-nucleophilic solvents, the first step consists of the metathesis polymerization of 3-chloro(bromo)-1-propyne followed by electrophilic cis–trans isomerization leading to polymers containing trans-cisoidal allyl chloride or bromide structural units. When the polymerization is performed in non-nucleophilic solvents, in the second step an intramolecular electrophilic addition followed by elimination takes place. The resulting polymers contain a highly conjugated cyclopentadiene ladder structure. When the polymerization is performed in nucleophilic aromatic solvents, the intramolecular electrophilic addition competes with the electrophilic substitution of the solvent resulting in polymers containing high concentrations of arylpropenyl structural units. Subsequently, depending on the nucleophilicity of the polymerization solvent, the polymer structure contains structural units based on cyclopentadiene and/or arylpropenyl groups.     

Nucleophilic trifluoromethylation of arylidenemalononitriles

A method for the nucleophilic trifluoromethylation of arylidenemalononitriles using Me₃SiCF₃ is described. The reaction is carried out in dimethylformamide in the presence of AcONa as a Lewis base, and affords products of Michael addition in high yield.     

Elemental F2 with Transannular Dienes: Regioselectivities and Mechanisms

Three reaction paths, namely, molecule‐induced homolytic, free radical, and electrophilic, were modeled computationally at the MP2 level of ab initio theory and studied experimentally for the reaction of F₂ with the terminal dienes of bicyclo[3.3.1]nonane series. The addition of fluorine is accompanied by transannular cyclization to the adamantane derivatives in which strong evidence for the electrophilic mechanism both in nucleophilic (acetonitrile) and non‐nucleophilic (CFCl₃, CHCl₃) solvents were found. The presence of KF in CFCl₃ and CHCl₃ facilitates the addition and substantially reduces the formation of tar products.     

Theoretical study of the Michael addition of acetylacetone to methyl vinyl ketone catalyzed by the ionic liquid 1‐butyl‐3‐methylimidazolium hydroxide

By performing density functional theory calculations, we have investigated the Michael addition of acetylacetone to methyl vinyl ketone in the absence and presence of the ionic liquid 1‐butyl‐3‐methylimidazolium hydroxide ([bmIm]OH). In the absence of ionic liquids, acetylacetone is firstly tautomerized to enol form and then takes place Michael addition to methyl vinyl ketone. As in the catalyzed Michael addition reaction, a bmIm⁺‐OH^? ion pair is introduced into the reaction system to model the effect of the ionic liquid environment on the reactivity. The calculated results show that the anion enhances nucleophilic ability of acetylacetone since the OH^? anion captures a proton to form an acetylacetone anion‐H₂O complex, and the cation improves the electrophilic ability of methyl vinyl ketone by forming intermolecular hydrogen‐bonds. Both the remarkable effects of the cation and anion on the reactivity of reactants promote this reaction, which take place more easily compared with uncatalyzed reaction. The calculated results show that the main product of the Michael addition is in its ketone form. Our study provides a detailed reaction mechanism of Michael addition catalyzed by basic ionic liquid [bmIm]OH and clearly reveal the catalytic role of ionic liquid in important chemical reaction. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Stereoselective aziridination of imines via ammonium ylides: A molecular electron density theory study

The highly trans-stereoselective reaction of ammonium salt ( AS 2 ) toward (E)-N-benzylidene-4-methylbenzenesulfonamide ( IM 4 ) in the presence of Na₂CO₃ leading to an aziridine derivative, trans -Az 6 , was theoretically studied using Molecular Electron Density Theory (MEDT) at the B3LYP/6-31G(d) computational level to probe energy transformation, selectivities, and molecular mechanism. The reaction starts by a nucleophilic substitution reaction between 1,4-diazabicyclo [2.2.2]octane ( DABCO ) and phenacyl bromide ( PB ) to form AS 2 which undergoes a proton abstraction by Na₂CO₃ to produce Ammonium Ylide ( AY 3) . Subsequently, nucleophilic addition of AY 3 to the double bond in IM 4 leads to form a betaine-like intermediate, namely, IN-Ta which named IN-Ta . Finally, trans -Az 6 is produced as a result of the nucleophilic attack of the negatively charged nitrogen atom on the carbon atom bearing DABCO in IN-Ta . Analysis of the relative Gibbs free energies shows that the ring closure step is the rate-determining step (RDS). By an investigation of the conceptual density functional theory, CDFT reactivity indices AY 3 and IM 4 are classified as a strong nucleophilic molecular system and as a strong electrophilic molecular system, respectively, which implies that the addition step of AY 3 to IM 4 has a high polar character. An analysis of the calculated electrophilic and nucleophilic Parr functions at the reactive sites of reagents clarifies the regioselectivity observed experimentally within the C₁–C₂ bond creation process.     

On the Mechanism of Bifunctional Squaramide‐Catalyzed Organocatalytic Michael Addition: A Protonated Catalyst as an Oxyanion Hole

A joint experimental–theoretical study of a bifunctional squaramide‐amine‐catalyzed Michael addition reaction between 1,3‐dioxo nucleophiles and nitrostyrene has been undertaken to gain insight into the nature of bifunctional organocatalytic activation. For this highly stereoselective reaction, three previously proposed mechanistic scenarios for the critical C?C bond‐formation step were examined. Accordingly, the formation of the major stereoisomeric products is most plausible by one of the bifunctional pathways that involve electrophile activation by the protonated amine group of the catalyst. However, some of the minor product isomers are also accessible through alternative reaction routes. Structural analysis of transition states points to the structural invariance of certain fragments of the transition state, such as the protonated catalyst and the anionic fragment of approaching reactants. Our topological analysis provides deeper insight and a more general understanding of bifunctional noncovalent organocatalysis.     

Base‐Dependent Stereodivergent Intramolecular Aza‐Michael Reaction: Asymmetric Synthesis of 1,3‐Disubstituted Isoindolines

The nucleophilic addition (A_N) / intramolecular aza‐Michael reaction (IMAMR) process on Ellman’s tert‐butylsulfinyl imines, bearing a Michael acceptor in the ortho position, is studied. This reaction affords 1,3‐disubstituted isoindolines with a wide range of substituents in good yields and diastereoselectivities. Interestingly, careful choice of the base for the aza‐Michael step allows either the cis or the trans diastereoisomers to be exclusively obtained. This stereodivergent cyclization has enabled the synthesis of C₂‐symmetric bisacetate‐substituted isoindolines. In addition, bisacetate isoindolines bearing two well‐differentiated ester moieties are also noteworthy because they may allow for the orthogonal synthesis of β,β′‐dipeptides using a single nitrogen atom as a linchpin.     

Coupling Reactions of Alkynyl Indoles and CO2 by Bicyclic Guanidine: Origin of Catalytic Activity?

Density functional theory calculations were used to investigate the three possible modes of activation for the coupling of CO₂ with alkynyl indoles in the presence of a guanidine base. The first of these mechanisms, involving electrophilic activation, was originally proposed by Skrydstrup et al. (Angew. Chem. Int. Ed . 2015 , 54 , 6682). The second mechanism involves the nucleophilic activation of CO₂. Both of these electrophilic and nucleophilic activation processes involve the formation of a guanidine‐CO₂ zwitterion adduct. We have proposed a third mechanism involving the bifunctional activation of the bicyclic guanidine catalyst, allowing for the simultaneous activation of the indole and CO₂ by the catalyst. We demonstrated that a second molecule of catalyst is required to facilitate the final cyclization step. Based on the calculated turnover frequencies, our newly proposed bifunctional activation mechanism is the most plausible pathway for this reaction under these experimental conditions. Furthermore, we have shown that this bifunctional mode of activation is consistent with the experimental results. Thus, this guanidine‐catalyzed reaction favors a specific‐base catalyzed mechanism rather than the CO₂ activation mechanism. We therefore believe that this bifunctional mechanism for the activation of bicyclic guanidine is typical of most CO₂ coupling reactions.     

Direct 1,4-difunctionalization of isoquinoline

The synthesis of 1,4-disubstituted isoquinoline derivatives was achieved in one step starting from isoquinoline. The process involved a nucleophilic addition in 1-position followed by an electrophilic trapping in 4-position. Interesting features were noted when C₂Cl₆ was used as the electrophile since different compounds could be isolated selectively only by adjusting the reaction parameters.     

Rhodium‐Catalyzed Alkene Difunctionalization with Nitrenes

The Rh^II‐catalyzed oxyamination and diamination of alkenes generate 1,2‐amino alcohols and 1,2‐diamines, respectively, in good to excellent yields and with complete regiocontrol. In the case of diamination, the intramolecular reaction provides an efficient method for the preparation of pyrrolidines, and the intermolecular reaction produces vicinal amines with orthogonal protecting groups. These alkene difunctionalizations proceed by aziridination followed by nucleophilic ring opening induced by an Rh‐bound nitrene generated in situ, details of which were uncovered by both experimental and theoretical studies. In particular, DFT calculations show that the nitrogen atom of the putative [Rh]₂=NR metallanitrene intermediate is electrophilic and support an aziridine activation pathway by N ??? N=[Rh]₂ bond formation, in addition to the N ??? [Rh]₂=NR coordination mode.     

Palladium‐Catalyzed Intramolecular Trost–Oppolzer‐Type Alder–Ene Reaction of Dienyl Acetates to Cyclopentadienes

A new approach to the synthesis of highly substituted cyclopentadienes, indenes, and cyclopentene‐fused heteroarenes by means of the Pd‐catalyzed Trost–Oppolzer‐type intramolecular Alder–ene reaction of 2,4‐pentadienyl acetates is described. This unprecedented transformation combines the electrophilic features of the Tsuji–Trost reaction with the nucleophilic features of the Alder–ene reaction. The overall outcome can be perceived as a hitherto unknown “acid‐free” iso‐Nazarov‐type cyclization. The versatility of this strategy was further demonstrated by the formal synthesis of paucifloral F, a resveratrol‐based natural product.     

A quantum‐chemical DFT study of the mechanism and regioselectivity of the 1,3‐dipolar cycloaddition reaction of nitrile oxide with electron‐rich ethylenes

The 1,3‐dipolar cycloaddition (13DC) reactions of nitrile‐oxide NO 1 with two ethylenes, enamine 2a and enamine 2b , were computationally studied using B3LYP/6‐31G(d) DFT methods. The two possible ortho and meta regioselective channels were characterized and analyzed. The moderate polarity of these 13DC reactions is related to the high nucleophilic character of both ethylenes, and the moderate electrophilic nature of the NO 1 , that accounts for the relatively low calculated activation energies. Analysis of different forms of energies along the different reaction channels indicates that the present 13DC reactions are completely ortho regioselective, accordingly to the experimental outcomes. Electron localization function analysis indicates that these 13DC reactions proceed via a nonconcerted (two‐stage) one‐step mechanism.     

Silver(I)‐Catalyzed Addition of Phenols to Alkyne Cobalt Cluster Stabilized Carbocations

A smooth catalytic method to use phenols as the nucleophilic partner in the Nicholas reaction has been developed. The method uses either Ag^I or Au^I catalysts with AgClO₄ or AgBF₄ as the most efficient catalysts tested. Neither additional additives nor cocatalysts were required and the formation of the corresponding phenol adducts occurred in excellent yields. The process has the single limitation of the inability of less nucleophilic phenols (4‐nitrophenol) to generate the corresponding adducts. Additionally, the reaction is highly diastereoselective. DFT calculations allow a catalytic cycle to be proposed that involves trimetallic intermediates; the rate‐determining step of the reaction is hydroxy‐group elimination in a cobalt–silver trimetallic intermediate.     

An Efficient Synthesis and Antibacterial Activity of Some Novel 2‐Azetidinone Derivatives of 4H‐1,2,4‐Triazoles Under Mild Conditions

We have synthesized the novel 2‐azetidinone derivatives by using Schiff bases of 1,2,4‐triazoles via a single step protocol. We used DABCO as a good homogenous, ecofriendly, highly reactive, easy to handle, and nontoxic catalyst. In DABCO catalyzed synthesis of active 2‐oxo‐azetidine, a highly electrophilic ketene intermediate can react with weakly nucleophilic (N═CH) linkage, which is used as the precursor for the cycloaddition reaction to deliver the desired products in excellent yields with protic solvents. In addition, the DABCO as an economically viable and readily available catalyst is soluble in almost all solvents and their salts easily filtered off from the reaction medium. Moreover, this new synthetic protocol features high conversion in green solvents and a straightforward procedure.     

New Insights into the Reactivity of Cisplatin with Free and Restrained Nucleophiles: Microsolvation Effects and Base Selectivity in Cisplatin–DNA Interactions

The reactivity of cisplatin towards different nucleophiles has been studied by using density functional theory (DFT). Water was considered first to analyze the factors that govern the transformation of cisplatin into more electrophilic aquated species by using an activation‐strain model. It was found that the selectivity and reactivity of cisplatin is a delicate trade‐off between strain and interaction energies and that the second chloride is a worse leaving group than the first. When similar studies were carried out with imidazole, guanine (G), and adenine (A), it was found that in general the second nucleophilic substitution reactions have lower activation barriers than the first ones. Finally, simulations of the structural restrictions imposed by the DNA scaffold in intra‐ and interstrand processes showed that the geometries of the reaction products are nonoptimal with respect to the unrestrained A and G nucleophiles, although the energetic cost is not considerable under physiological conditions, which thus permits nucleophilic substitution reactions that lead to highly distorted DNA.     

Understanding the reactivity and regioselectivity of [3 + 2] cycloaddition reactions between substituted nitrile oxides and methyl acrylate. A molecular electron density theory study

The [3 + 2] cycloaddition (32CA) reactions of three nitrile oxides (NOs) (R‐CNO; R = Ph, CO₂Me, and Br) with methyl acrylate (MA) have been theoretically studied within the molecular electron density theory. Topological analysis of the electron localization function of these NOs permits to establish that they will participate in zw‐type 32CA reactions. Analysis of the conceptual DFT indices indicates that these zw‐type 32CA reactions will have a low polar character as a consequence of the relatively low electrophilic character of MA and the low nucleophilic character of NOs, in agreement with the global electron density transfer computed at the corresponding TSs. The activation enthalpies associated with these 32CA reactions range from 8.2 to 12.7 kcal·mol^?1. The presence of the bromide atom provokes the larger acceleration. While the 32CA reaction involving the CO₂Me substituted NO is highly ortho regioselective, the other two reactions are poorly ortho regioselective. A bonding evolution theory study of the more favorable ortho regiosiomeric channel associated with the 32CA reaction involving the Br substituted NO indicates that this reaction is associated to a nonconcerted two‐stage one‐step mechanism, in which the activation energy is mainly related to the initial rupture of the C? N triple bond of the NO.     

C-H bond activation of methane in aqueous solution: a hybrid quantum mechanical/effective fragment potential study

In this study, we investigated the C? H bond activation of methane catalyzed by the complex [PtCl₄]^2?, using the hybrid quantum mechanical/effective fragment potential (EFP) approach. We analyzed the structures, energetic properties, and reaction mechanism involved in the elementary steps that compose the catalytic cycle of the Shilov reaction. Our B3LYP/SBKJC/cc‐pVDZ/EFP results show that the methane activation may proceed through two pathways: (i) electrophilic addition or (ii) direct oxidative addition of the C? H bond of the alkane. The electrophilic addition pathway proceeds in two steps with formation of a σ‐methane complex, with a Gibbs free energy barrier of 24.6 kcal mol^?1, followed by the cleavage of the C? H bond, with an energy barrier of 4.3 kcal mol^?1. The activation Gibbs free energy, calculated for the methane uptake step was 24.6 kcal mol^?1, which is in good agreement with experimental value of 23.1 kcal mol^?1 obtained for a related system. The results shows that the activation of the C? H bond promoted by the [PtCl₄]^2? catalyst in aqueous solution occurs through a direct oxidative addition of the C? H bond, in a single step, with an activation free energy of 25.2 kcal mol^?1, as the electrophilic addition pathway leads to the formation of a σ‐methane intermediate that rapidly undergoes decomposition. The inclusion of long‐range solvent effects with polarizable continuum model does not change the activation energies computed at the B3LYP/SBKJC/cc‐pVDZ/EFP level of theory significantly, indicating that the large EFP water cluster used, obtained from Monte Carlo simulations and analysis of the center‐of‐mass radial pair distribution function, captures the most important solvent effects. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Highly-Selective Construction of Aza-Fused Pyrrolo Isoquinoline Derivatives

A novel Rh(III)-catalyzed cascade C−H activation/annulation/nucleophilic attack/Michael addition of 2-phenyloxazoles with maleimides for highly-selective construction of pyrroloisoquinoline derivatives through conditions control is reported. In this reaction, oxazoles were used both as the directing group and potential functionalized reagents, H₂O was the nucleophile. The notable features of this protocol include atom economy and highly regioselectivity.     

Diastereoselective [3+2] Annulation of Aromatic/Vinylic Amides with Bicyclic Alkenes through Cobalt‐Catalyzed C−H Activation and Intramolecular Nucleophilic Addition

A highly diastereoselective method for the synthesis of dihydroepoxybenzofluorenone derivatives from aromatic/vinylic amides and bicyclic alkenes is described. This new transformation proceeds through cobalt‐catalyzed C?H activation and intramolecular nucleophilic addition to the amide functional group. Transition‐metal‐catalyzed C?H activation reactions of secondary amides with alkenes usually lead to [4+2] or [4+1] annulation; to the best of our knowledge, this is the first time that a [3+2] cycloaddition is described in this context. The reaction proceeds under mild conditions and tolerates a wide range of functional groups. Mechanistic studies imply that the C?H bond cleavage may be the rate‐limiting step.