Deciphering the mechanistic dichotomy in the cyclization of 1-(2-ethynylphenyl)-3,3-dialkyltriazenes: competition between pericyclic and pseudocoarctate pathways

The mechanistic aspects of the cyclization of (2-ethynylphenyl)triazenes under both thermal and copper-mediated conditions are reported. For cyclization to an isoindazole, a carbene mechanistic pathway is proposed. The carbene intermediate can react with oxygen, dimerize to give an alkene, or be trapped either intermolecularly (using 2,3-dimethyl-2-butene to generate a cyclopropane) or intramolecularly (using a biphenyl moiety at the terminus of the acetylene to form a fluorene). Density-functional theory (DFT) calculations support a pseudocoarctate pathway for this type of cyclization. Thermal cyclization to give a cinnoline from (2-ethynylphenyl)triazenes is proposed to occur through a pericyclic pathway. DFT calculations predict a zwitterionic dehydrocinnolinium intermediate that is supported by deuterium trapping studies as well as cyclizations performed using a 2,2,6,6-tetramethylpiperidine moiety at the 3-position of the triazene.     

Experimental and theoretical investigation of the coarctate cyclization of (2-Ethynylphenyl)phenyldiazenes

A new route to substituted 2-phenyl-2H-indazoles through the cyclization of (2-ethynylphenyl)phenyldiazenes is presented. A coarctate reaction pathway forms the isoindazole carbene under neutral conditions, at moderate temperatures, and without the requirement of a carbene stabilizer. A wide variety of previously unknown diazene precursors was synthesized and cyclized. Trapping of the carbene with a silyl alcohol followed by deprotection affords the 3-hydroxymethyl-2-phenyl-2H-indazoles in good overall yield. The free carbene could also be trapped as a [2 + 1] cycloadduct with 2,3-dimethyl-2-butene.     

Understanding the mechanism of non-polar Diels-Alder reactions. A comparative ELF analysis of concerted and stepwise diradical mechanisms

The electron-reorganization along the concerted and stepwise pathways associated with the non-polar Diels-Alder reaction between cyclopentadiene (Cp, 1) and ethylene (2) has been studied using the topological analysis of the electron localization function (ELF) at the B3LYP/6-31G(d) level of theory. ELF results for the concerted mechanism stresses that the electron-reorganization demanded on the diene and ethylene reagents to reach two pseudo-diradical structures is responsible for the high activation energy. A comparative ELF analysis of some relevant points of the non-polar Diels-Alder reaction between Cp and styrene (10) suggests that these concerted mechanisms do not have a pericyclic electron-reorganization.     

Cyclization of 1-(2-alkynylphenyl)-3,3-dialkyltriazenes: a convenient,high-yield synthesis of substituted cinnolines and isoindazoles

A new route to isoindazoles and cinnolines through the cyclization of (2-alkynylphenyl)triazenes under neutral conditions is presented. The products that result from heating the starting triazenes depend on both the type of alkyne ortho to the triazene functionality and the temperature used. Butadiyne moieties ortho to dialkyltriazenes yield bis-isoindazole dimers when heated to 150 degrees C in MeI. A requirement for cyclization in MeI is that the (2-alkynylphenyl)triazene must contain a suitably electron-withdrawing substituent on the phenyl ring to deactivate the triazene toward methylation-induced decomposition to an iodoarene. Ethynyl moieties ortho to dialkyltriazenes yield both isoindazole dimers as well as 3-formylisoindazoles when subjected to the same conditions. Replacing MeI with 1,2-dichlorobenzene as solvent allows for the general cyclization of (2-ethynylphenyl)dialkyltriazenes. Heating to 170 degrees C results in a mixture of isoindazole and cinnoline products, whereas the cinnolines are produced exclusively in high yield at 200 degrees C. Alternatively, the isoindazoles can be obtained in good to excellent yield by stirring a 1,2-dichloroethane solution of the starting triazene with CuCl overnight at 50 degrees C.     

Biscyclization reactions in butadiyne- and ethyne-linked triazenes and diazenes: concerted versus stepwise coarctate cyclizations

A series of alkyne-linked bis-2H-indazoles has been prepared by the double cyclization of ethyne- or butadiyne-linked phenyltriazene or phenyldiazene moieties. Even though there are two five-membered ring cyclizations and several triple bond shifts involved, the reactions proceed rapidly under neutral conditions with mild heating, affording the heterocycles in excellent yields. DFT calculations, in agreement with experimental observations, indicate that the reactions: (1) occur via a very short-lived carbene intermediate, (2) are concerted via an asymmetrical transition state, or (3) are even synchronous, with as many as 16 bonds that are made or broken simultaneously. The biscyclizations presented herein strikingly illustrate the concept of coarctate reactions, the stabilization of transition states by coarctate M?bius aromaticity, the ethynologation principle, and the stereochemical rules.     

Origin of the synchronicity in bond formation in polar Diels-Alder reactions: an ELF analysis of the reaction between cyclopentadiene and tetracyanoethylene

The origin of the synchronicity in C-C bond formation in polar Diels-Alder (P-DA) reactions involving symmetrically substituted electrophilic ethylenes has been studied by an ELF analysis of the electron reorganization along the P-DA reaction of cyclopentadiene (Cp) with tetracyanoethylene (TCE) at the B3LYP/6-31G* level. The present study makes it possible to establish that the synchronicity in C-C bond formation in P-DA reactions is controlled by the symmetric distribution of the electron-density excess reached in the electrophile through the charge transfer process, which can be anticipated by an analysis of the spin electron-density at the corresponding radical anion. The ELF comparative analysis of bonding along the DA reactions of Cp with ethylene and with TCE asserts that these DA reactions, which have a symmetric electron reorganization, do not have a cyclic electron reorganization as the pericyclic mechanism states. Due to the very limited number of cases of symmetrically substituted ethylenes, we can conclude that the synchronous mechanism is an exception of DA reactions.     

Two unusual, competitive mechanisms for (2-ethynylphenyl)triazene cyclization: pseudocoarctate versus pericyclic reactivity

The cyclization of (2-ethynylphenyl)triazenes in ODCB at 200 degrees C gives exclusively cinnolines, whereas addition of CuCl to 1,2-dichloroethane solutions of the triazenes at 50 degrees C results in the sole formation of isoindazoles. DFT calculations and deuterium labeling studies suggest the intermediacy of a 3-dehydrocinnolinium ion, produced through a pericyclic transition state. Calculations and trapping studies strongly implicate a carbene intermediate in isoindazole formation, which proceeds through a pseudocoarctate transition state.     

Understanding the electronic reorganization along the nonpolar [3 + 2] cycloaddition reactions of carbonyl ylides

The nonpolar [3 + 2] cycloaddition (32CA) reaction of the carbonyl ylide (CY) 23 with tetramethylethylene (TME) 24 has been studied with DFT methods at the B3LYP/6-31G* level. This cycloaddition reaction, which has a very low activation energy of 4.7 kcal/mol, takes place through a synchronous transition structure. A topological analysis of the ELF along the 32CA reaction provides a new scope of the electronic structure of CY 23 as a pseudodiradical species offering a sound explanation of the high reactivity of this CY in nonpolar reactions. In addition, this analysis points to the nonparticipation of the oxygen lone pairs in the 32CA reaction. This cycloaddition can be seen as a pseudodiradical attack of the terminal carbon atoms of the CY 23 on the π system of TME 24. Therefore, the present study establishes that this 32CA reaction, which is not a pericyclic electron reorganization, may be electronically classified as a [2n + 2π] process.     

Synthesis and spectroscopy of anthracene-containing linear and ‘T’-shaped π-conjugated ligands

A range of new π-conjugated ethynyl- and diethynyl-benzene ligands has been synthesised and their spectroscopic characterisation carried out, most notably via IR and ¹H NMR. X-ray crystal structures were obtained for three of these ligands and one unusual ruthenium complex. Both the 4-ethynyl- and 2,5-diethynyl-benzene cores of these compounds have been functionalised through organic transformations by addition of an 9-anthracenyl. This has been attached via a range of linker moieties that vary in both their length and degree of π-conjugation. This has given rise to two groups of compounds with either a linear, e.g., 9-(2-(4-ethynylphenyl)ethynediyl)anthracene and 9-(2-(4-ethynylphenyl)ethyl)anthracene, or ‘T’-shaped morphologies, e.g., 9-(2-(2,5-diethylnylphenyl)ethyl)anthracene.     

Ethynylogization of a coarctate fragmentation

Coarctate reactions form a separate class of elementary closed-shell processes in addition to polar and pericyclic reactions. Hence, they also follow a different homology principle. Whereas vinylogous polar and pericyclic reactions differ in the length of the reacting system by a double bond, coarctate reactions can be homologized (ethynylogized) by extending a known system by a triple bond. The prediction, which is based on theoretical considerations, is confirmed experimentally by the fragmentation of cyclopropylethynyl nitrene to cyano acetylene and ethylene, a reaction that is "ethynyloguous" to the known fragmentation of cyclopropyl nitrene to ethylene and HCN.     

Thermal and Photochemical Transformations of Hetero-1,3,5-hexatrienes into Five-Membered Rings—Possible Pericyclic Reactions

Heterosubstituted 1,3,5-hexatrienes undergo thermal and photochemical cyclizations, most of which can be viewed as pericyclic reactions. Numerous cyclizations of this type have been reported in the literature. This article presents a systematic account of such reactions, classified according to the number and nature of the heteroatoms.     

A copper(i)-catalyzed reaction of 2-(2-ethynylphenyl)oxirane, sulfonyl azide, with 2-isocyanoacetate

A novel and straightforward synthetic protocol for the efficient construction of 3',5'-dihydro-1H-spiro[benzo[d]oxepine-2,4'-imidazoles] through a copper(i)-catalyzed reaction between 2-(2-ethynylphenyl)oxirane, sulfonyl azide, and 2-isocyanoacetate is described.     

Olefin epoxidation by molybdenum peroxo compound: molecular mechanism characterized by the electron localization function and catastrophe theory

The oxygen atom transfer reaction from the Mimoun-type complex MoO(η(2)-O(2))(2)OPH(3) to ethylene C(2)H(4) affording oxirane C(2)H(4)O has been investigated within the framework of the Bonding Evolution Theory in which the corresponding molecular mechanism is characterized by the topological analysis of the electron localization function (ELF) and Thom's catastrophe theory (CT). Topological analysis of ELF and electron density analysis reveals that all Mo-O bonds in MoO(η(2)-O(2))(2)OPH(3) and MoO(2)(η(2)-O(2))OPH(3) belong to closed-shell type interactions though negative values of total energy densities E(e)(r(BCP)) imply some covalent contribution. The peroxo O(i)-O(j) bonds are characterized as charge-shift or protocovalent species in which pairs of monosynaptic basins V(3)(O(i)), V(3)(O(j)) with a small electron population of ~0.25e each, are localized between core basins C(O(i)), C(O(j)). The oxygen transfer reaction from molybdenum diperoxo complex MoO(η(2)-O(2))(2)OPH(3) to C(2)H(4) system can be described by the following consecutive chemical events: (a) protocovalent peroxo O(2)-O(1) bond breaking, (b) reduction of the double C(1)=C(2) bond to single C(1)-C(2) bond in ethylene, (c) displacement of oxygen O(1) with two nonbonding basins, V(i=1,2)(O(1)), (d) increase of a number of the nonbonding basins to three (V(i=1,2,4)(O(1))); (e) reorganization and reduction in the number of nonbonding basis to two basins (V(i=1,4)(O(1))) resembling the ELF-topology of the nonbonding electron density in oxirane, (e) formation of the first O(1)-C(2) bond in oxirane, (f) C(2)-O(1)-C(2) ring closure, (g) formation of singular nonbonding basin V(O(2)) in new Mo=O(2) bond. The oxygen atom is transferred as an anionic moiety carrying a rather small electronic charge ranging from 0.5 to 0.7e.     

Cyclization of electron-deficient cyclopentadienone with 2-alkenyl and 2-alkynylamines via sequential pericyclic reaction pathway.

The pericyclic reactions of 2,5-bis(methoxycarbonyl)-3,4-diphenylcyclopentadienone (1a) with both allylic and propargylic amines have been investigated. The reaction proceeded via initial formation of the 1,4 adducts followed by the ene cyclization and/or sequential pericyclic reactions depending upon the structures of the amines. The reaction of 1a with diallylamine (2a) gave the tetracyclic compound (3a). On the other hand, the reaction of 1a with 2-propynylamine (2c) gave exclusively the bicyclic compound (5c). In the reactions with the secondary 2-propynylamines (2d,e), the tetracyclic compounds (3d,e) were exclusively formed. The reactions of 1a with alpha-branched primary 1,1-dialkyl-2-propynylamines (2f,g) gave mixtures of 3- and 5-type compounds. The tetracyclic compounds 3 were formed from the intramolecular [4+2]pi cycloadditions of the [1,5]-sigmatropic rearrangement products of the 1,4 adducts of 1a and 2, followed by the [1,5]-sigmatropic rearrangement of hydrogen and dehydrogenation. The bicyclic compounds 5 were derived from the [2pi+2pi+2sigma] reaction of the 1,4 adducts of 1a and 2. The one-pot multistage sequential pericyclic reactions were discussed on the basis of the X-ray crystallographic structures and the MO calculation data.     

Synthesis of functionalized diaryl selenides by the first [3+3] cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes with organoselenium compounds

Functionalized diaryl selenides were prepared by the first [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with organoselenium compounds (i.e., 2-(phenylselanyl)-3-silyloxy-3-en-1-ones).     

Topographical analyses of homonuclear multiple bonds between main group elements

Recent experiments have resulted in the completion of the series of Group 14 and Group 15 element double-bond systems, R(n)E=ER(n) (E = C - Pb, n = 2; E = N - Bi, n = 1). Furthermore, new families of multiple-bonded species have been discovered, such as the radical anion [RSnSnR](-) , the close ion pairs [RE(mu2Na)2ER] (E = Ge,Sn), and a digallyne [RGa(mu2Na)2GaR] for which a Ga=Ga triple bond was formulated. Some of these compounds show classical multiple bond features (i.e. the dipnictogens RE=ER, E=N-Bi) in the sense that planar structures with short E-E distances are observed. However, many (i.e. R2E=ER2, E = Si - Pb) do not behave as expected for compounds with multiple bonds. They have trans bent structures, show enormous variation in their E-E distances, and some dissociate easily under E-E bond cleavage in solution. These properties raised doubts as to whether these compounds can be formulated as multiple-bonded systems. Using the electron localization function (ELF) it is possible to clearly show the topographical similarities between classical and nonclassical multiple bonds; ELF divides these systems into unslipped (classical) and slipped (nonclassical) systems. ELF can also be employed to confirm the nonexistence of multiple bonds. Therefore, topographical analyses using ELF are useful to categorize a bonding system. In particular, the bonds in the heavier Group 14 double systems and the Ga-Ga bond in digallyne are clearly shown by this method as slipped double and triple bonds, respectively.     

Understanding the electronic reorganization in the thermal isomerization reaction of trans‐3,4‐dimethylcyclobutene. Origins of outward Pseudodiradical {2n + 2π} torquoselectivity

The thermal isomerization reaction of trans‐3,4‐dimethylcyclobutene (1,2,3,4‐DMC) to produce the isomer (2E, 4E)‐hexadiene have been studied using density functional theory at the B3LYP/6‐31+G level. For this reaction, two different channels of the conrotatory torquoselectivity allowing the formation of the two isomeric (E,E) and (Z,Z) have been characterized. The isomer (Z,Z) occurs through the inward conrotatory mechanism, whereas the isomer (E,E) occurs through the outward conrotatory mechanism. The outward conrotatory is favored by 11.3 kcal/mol with respect to inward conrotatory one. This behavior is consistent with the thermodynamic properties: enthalpy, free energy, and entropy calculated in both reaction pathways. The topological analysis of the electron localization function at the outward conrotatory transition state explicated the electronic reorganization through a pseudodiradical {2n + 2π} process and not a pericyclic reorganization. © 2012 Wiley Periodicals, Inc.     

Electron localization function at the correlated level

The electron localization function (ELF) has been proven so far a valuable tool to determine the location of electron pairs. Because of that, the ELF has been widely used to understand the nature of the chemical bonding and to discuss the mechanism of chemical reactions. Up to now, most applications of the ELF have been performed with monodeterminantal methods and only few attempts to calculate this function for correlated wave functions have been carried out. Here, a formulation of ELF valid for mono- and multiconfigurational wave functions is given and compared with previous recently reported approaches. The method described does not require the use of the homogeneous electron gas to define the ELF, at variance with the ELF definition given by Becke. The effect of the electron correlation in the ELF, introduced by means of configuration interaction with singles and doubles calculations, is discussed in the light of the results derived from a set of atomic and molecular systems.     

通过价层电子密度分析展现分子电子结构

迄今已有众多实空间函数被提出用来揭示化学上感兴趣的分子电子结构特征,例如化学键、孤对电子和多中心电子共轭。在这些分析方法中,电子定域化函数(ELF)、电子密度的拉普拉斯(∇²ρ)和变形密度(ρ_def)被广泛用于实际研究。众所周知,分析分子的总电子密度无法像以上提及的方法那样展现出与分子电子结构有关的丰富的信息。但是,在本文中,通过数个实例以及通过与ELF、∇²ρ和ρ_def的对比,我们指出若只关注价层电子密度分布,分子电子结构特征也是可能被探究的。我们发现对大多数情况,对非常简单的价层电子密度的分析也可以给出与ELF、∇²ρ和ρ_def分析类似的信息,并且这种分析具有计算复杂度更低的额外优点。我们希望本文的工作可以使得化学家们关注长期被忽视的价层电子密度所具有的重要价值。也值得注意的是,价层电子密度分析并非完全没有缺点,当这种方法无法提供丰富信息的时候,研究者仍需借助于其它类型的分析手段。     

Acetoxyl group directed cyclization promoted by SmI2: directing group determined stereocomplementarity

Complete reversal of diastereoselectivity was observed in the SmI(2)-promoted ketyl-olefin coupling cyclizations of the hydroxy ketone or aldehyde and its acetate. For example, the stereodivergent synthesis of the epimeric five-membered-ring alcohols 2 and 4 has been accomplished through the SmI(2)-induced ketyl-olefin coupling cyclizations of the delta-hydroxy ketone 1 and delta-acetoxy ketone 3.