Nature of bonding in the cyclization reactions of (2-Ethynylphenyl)triazene and 2-Ethynylstyrene

The topological analysis of the electron localization function (ELF) has been applied to explore the nature of bonding in thermal cyclizations of (2-ethynylphenyl)triazene and 2-ethynylstyrene. These processes have been proposed to occur through both five- (i.e., coarctate) and six-membered (i.e., pericyclic) transition states. The analysis of electron delocalization, as measured from an irreducible ELF f-localization domain reduction diagram, allows us to characterize these cyclizations of 2-ethynylstyrene in terms of a more pronounced pericyclic or coarctate character than those associated with (2-ethynylphenyl)triazene. The latter evolve through pseudopericyclic and pseudocoarctate pathways. It is found that ELF results are also in good agreement with recent magnetic evidence data obtained from the anisotropy of induced current density (ACID) calculations.     

Coarctate cyclization reactions: a primer

The cleavage of five-membered heterocycles possessing an exocyclic carbene or nitrene to form conjugated ene-ene-yne systems has been documented for over 40 years; however, the reverse reaction, using a conjugated "ene-ene-yne" precursor to form a heterocycle is a relatively new approach. Over the past decade, the Haley and Herges groups have studied computationally and experimentally the cyclization of the "hetero-ene-ene-yne" motif via an unusual class of concerted reactions known as coarctate reactions. This feature article details our synthetic and mechanistic work involving triazene-arene-alkynes and structurally-related systems to generate heterocycles using coarctate chemistry.     

Rearrangement of azirine intermediates to nitriles: Theoretical study of cleavage of 3,4-dihydro-1aH-azirine[2,3-c]pyrrol-2-one to cyanoketene–formaldimine complex

A detailed investigation of the reaction path for the thermal rearrangement of 3,4-dihydro-1aH-azirine[2,3-c]pyrrol-2-one to yield a cyanoketene–formaldimine complex is carried out at the MP2/6-31G* and B3LYP/6-31G* levels of theory. The ring opening of the five-membered pyrrolinone ring and the formation of the nitrile group takes place in a concerted manner, presenting a significant strain energy release and allowing for an electronic stabilization by coarctate conjugation of the transition structure (TS). These two factors make possible a moderate energy barrier. Although the structural features B3LYP/6-31G* theoretical levels, it is found that the MP2 energy barrier (28.8) CCSD(T)/6-31G*//MP2/6-31G* value (17.1 kcal/mol). The complex electronic rearrangement can be rationalized using the theory of coarctate transition structures developed by Herges as the evolution of an azirine structure without referring to a hypothetical vinyl nitrene intermediate. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 912–922, 1998     

Reaction of lithium diethylamide with an alkyl bromide and alkyl benzenesulfonate: origins of alkylation, elimination, and sulfonation

A combination of NMR, kinetic, and computational methods are used to examine reactions of lithium diethylamide in tetrahydrofuran (THF) with n-dodecyl bromide and n-octyl benzenesulfonate. The alkyl bromide undergoes competitive S(N)2 substitution and E2 elimination in proportions independent of all concentrations except for a minor medium effect. Rate studies show that both reactions occur via trisolvated-monomer-based transition structures. The alkyl benzenesulfonate undergoes competitive S(N)2 substitution (minor) and N-sulfonation (major) with N-sulfonation promoted at low THF concentrations. The S(N)2 substitution is shown to proceed via a disolvated monomer suggested computationally to involve a cyclic transition structure. The dominant N-sulfonation follows a disolvated-dimer-based transition structure suggested computationally to be a bicyclo[3.1.1] form. The differing THF and lithium diethylamide orders for the two reactions explain the observed concentration-dependent chemoselectivities.     

Synthesis of 1-substituted benzo[c]isoxazol-3(1H)-imines via tandem nitroso-ene/intramolecular cyclizations of 2-nitrosobenzonitrile

Instead of reacting via the expected coarctate cyclization pathway, 2-nitrosobenzonitrile undergoes a tandem nitroso-ene/intramolecular cyclization to form benzo[c]isoxazol-3(1H)-imines in very good yields under neutral conditions and at moderate temperatures. Treatment of three of the imines with HBF4 results in dimerization/condensation to furnish unusual, delocalized cationic systems.     

Reactions of phosphate and phosphorothiolate diesters with nucleophiles: comparison of transition state structures

A series of methyl aryl phosphorothiolate esters (SP) were synthesized and their reactions with pyridine derivatives were compared to those for methyl aryl phosphate esters (OP). Results show that SP esters react with pyridine nucleophiles via a concerted S(N)2(P) mechanism. Br?nsted analysis suggests that reactions of both SP and OP esters proceed via transition states with dissociative character. The overall similarity of the transition state structures supports the use of phosphorothiolates as substrate analogues to probe mechanisms of enzyme-catalyzed phosphoryl transfer reactions.     

Reactions in the conjugated 'ene-ene-yne' manifold: five-membered ring fragmentation and ring formation via coarctate/pseudocoarctate mechanisms

The fragmentation of a 5-membered heteroaromatic ring to afford a conjugated ene-ene-yne skeleton, and the corresponding reverse process, cyclization of the hetero-ene-ene-yne motif to generate a variety of heterocyclic systems, are the subject of this review. These synthetically useful reactions, which proceed through a coarctate/pseudocoarctate mechanistic pathway, are unique in that they involve the generation of either a carbene or nitrene intermediate, and provide access to hard to obtain heterocyclic or ene-ene-yne structures. While fragmentation of heteroaromatic rings containing a exocyclic carbene or nitrene has been well documented in the literature for over 40 years, the use of hetero-ene-ene-yne precursors to synthesize heterocycles is a relatively new approach that is generating much interest in the literature. This review highlights both the synthetic and mechanistic aspects of these unique reactions.     

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.     

Theoretical study of the gas-phase thermolysis reaction of alkyl (ethyl,isopropyl, and tert-butyl) N,N-dimethylcarbamates and N,N-diethylcarbamates

Theoretical studies on the thermolysis in the gas phase of alkyl N,N-dialkylcarbamates were carried out using ab initio theoretical methods, at the MP2/6-31G(d), MP2/6-31++G(d,p) and MP2/6-311++G(2d,p)//MP2/6-31G(d) levels. The reactions have two steps: the first one corresponds to the formation of an alkene and a neutral dialkylcarbamic acid intermediate via a six-membered cyclic transition state; the second one is the decarboxylation of this intermediate via a four-membered cyclic transition state, leading to carbon dioxide and the corresponding dialkylamine. The progress of the reactions was followed by means of the Wiberg bond indices. The results indicate that the transition states have character intermediate between reactants and products, and the calculated synchronicities show that the reactions are slightly asynchronous. The bond-breaking processes are more advanced than the bond-forming ones, indicating a bond deficiency in the transition states. The rate constants calculated for all the reactions agree very well with the available experimental data.From the Proceedings of the 28th Congreso de Químicos Teóricos de Expresión Latina (QUITEL 2002)     

Isotope effects and the mechanism of fragmentation of epoxy imino-1,3,4-oxadiazolines

The fragmentation of an epoxy imino-1,3,4-oxadiazoline is studied by a combination of isotope effects and theoretical calculations. Significant primary ¹³C isotope effects are observed at the two oxadiazoline carbons but negligible isotope effects are observed at the remaining carbons. This is consistent with a rate-limiting fragmentation of the oxadiazoline without fragmentation of the adjacent epoxide ring. Theoretical calculations support this interpretation. This formal coarctate reaction avoids two complicated coarctate fragmentations in favor of a multi-step mechanism with a simple coarctate final step.     

β-羟基丙醛基态与激发态氢迁移反应的从头算研究

本文用从头算RHF和UHF方法在3-21G基组上研究了β-羟基丙醛基态和激发态分解为甲醛和乙烯醇的反应机理。优化得到了各反应途径的过渡态和中间体, 其结果为: 基态β-羟基丙醛经过一个六元环过渡态和一个氢键中间体形成产物, 反应属于氢迁移和断键的协同过程; 激发三态β-羟基丙醛的分解途径首先经过一个氢迁移六元环过渡态形成双自由基中间体, 然后该中间体的分解包括两条相互竞争的途径, 它们各自经过一个断碳碳键的过渡态和一个氢键激-基态配合物中间体而形成两类产物, 一类为甲醛的基态和乙烯醇的激发态, 另一类为甲醛的激发态和乙烯醇的基态。激发态反应的两条通道均属于先氢迁移后断键分解的分步过程, 且反应的第二步为速控步骤。计算结果表明, 激发态反应活化位垒都比基态的低。     

Nucleophilic substitution at phosphorus (S(N)2@P): disappearance and reappearance of reaction barriers

Pentacoordinate phosphorus species play a key role in organic and biological processes. Yet, their nature is still not fully understood, in particular, whether they are stable, intermediate transition complexes (TC) or labile transition states (TS). Through systematic, theoretical analyses of elementary S(N)2@C, S(N)2@Si, and S(N)2@P reactions, we show how increasing the coordination number of the central atom as well as the substituents' steric demand shifts the S(N)2@P mechanism stepwise from a single-well potential (with a stable central TC) that is common for substitution at third-period atoms, via a triple-well potential (featuring a pre- and post-TS before and after the central TC), back to the double-well potential (in which pre- and postbarrier merge into one central TS) that is well-known for substitution reactions at carbon. Our results highlight the steric nature of the S(N)2 barrier, but they also show how electronic effects modulate the barrier height.     

Aromaticity and Pericyclic Reactions

Pericyclic reactions formally resemble the conversion of one Kekulé structure into another; the transition state may be “aromatic”, “nonaromatic”, or “antiaromatic”. Thermally induced pericyclic reactions proceed preferentially via aromatic transition states whereas their photochemical counterparts lead to products that are formed via antiaromatic transition states.     

Infrared frequency-modulation probing of product formation in alkyl + O2 reactions. Part IV. Reactions of propyl and butyl radicals with O2

The time-resolved production of HO2 in the Cl-initiated oxidation of iso- and n-butane is measured using continuous-wave (CW) infrared frequency modulation spectroscopy between 298 and 693 K. The yield of HO2 is determined relative to the Cl2/CH3OH/O2 system. As in studies of smaller alkanes, the branching fraction to HO2 + alkene in butyl + O2 displays a dramatic rise with increasing temperature between about 550 and 700 K (the "transition region") which is accompanied by a qualitative change in the time behavior of the HO2 production. At low temperatures the HO2 is formed promptly; a second, slower production of HO2 is responsible for the bulk of the increased yield in the transition temperature region. In contrast to reactions of smaller alkyl radicals with O2, the total HO2 yield in the butyl radical reactions appears to remain significantly below 1 up to 700 K, implying a significant role for OH-producing channels. The slower HO2 production in butane oxidation displays an apparent activation energy similar to that measured for smaller alkyl + O2 reactions, suggesting that the energetics of the HO2 elimination transition state are similar for a broad range of R + O2 systems. A combination of QCISD(T) based characterizations of the propyl and butyl + O2 potential energy surfaces and master equation based characterization of the propyl + O2 kinetics provide the framework for explanation of the experimentally observed HO2 production in Cl-initiated propane and butane oxidation. These calculations suggest that the HO2 elimination channel is similar in all reaction systems, and that hydroperoxyalkyl (QOOH) species produced by internal H-atom abstraction in RO2 can provide a path to OH formation. However, the QOOH formed by the energetically favorable 1,5 isomerization (via a six-membered ring transition state) generally experiences significant barriers (relative to the radical + O2 reactants) to the production of an oxetane + OH. In contrast, the barriers to forming OH + an oxirane or an oxolane, via 1,4 or 1,6 isomerizations, respectively, are generally below reactants.     

硅苯与HX (X=F,OH, NH2)的1,2-及1,4-加成反应

采用密度泛函理论方法在B3LYP/6-311++G(d,p)水平上, 研究了硅苯与HX (X=F, OH, NH₂)的1,2-及1,4-加成反应的微观机理和势能剖面, 考察了Si 原子上的取代基及四氢呋喃溶剂对反应势能剖面的影响. 研究结果表明, 标题反应有两种可能的机理: (1) 硅苯与一个HX (X=F, OH, NH₂)分子先形成中间复合物, 然后经过四元环过渡态(机理1)生成最终产物; (2) 硅苯与两个HX分子先形成中间复合物, 然后经过六元环过渡态(机理2)生成另一中间复合物, 该中间复合物脱去一个HX分子形成最终产物. 机理2 在动力学上远较机理1 有利. 1,2-及1,4-加成产物哪种优先形成由动力学控制且与X基团的种类有关. HX在气相中参与加成反应从易到难的次序为: HF>H₂O>NH₃. Si 原子上具有较强供电子和吸电子性质的取代基, 在热力学和动力学上均有利于反应的进行, 但具有较大体积的2,4,6-三甲基苯基取代基对反应反而不利. 四氢呋喃溶剂在热力学上不利于硅苯与HX的1,2-及1,4-加成反应, 在动力学上对HF或H₂O作为加成试剂的反应也不利, 但对NH3作为加成试剂的反应反而有利.     

Theoretical study of the oxidation reactions of methylacrylic acid and methyl methacrylate by triplet O2

The oxidations of organic compounds and polymers by triplet O2 were called "dark oxidation" or "auto-oxidation", in contrast to their "photo-oxidation" by singlet O2. To study the relevant dark oxidation mechanism we take methylacrylic acid (MAA) and methyl methacrylate (MMA) as prototypes to study their reactions with triplet O2 by performing density functional theory calculations. Two reaction channels, the C-H bond oxidation and C=C bond oxidation, have been characterized in detail. The structures of the initial contact charge-transfer complexes, intermediates, transition states, and final oxides involved in the reactions have been localized at the UB3LYP/6-311+G(d,p) level. It is found that the C-H bond in the methyl group connected to the C=C bond presents relatively higher reactivity toward triplet O2 than the C=C bond itself. Thus, the reactions are expected to proceed via the C-H bond oxidation branch at room temperature and also via C=C bond oxidation at elevated temperature. In this sense, an effective method for preventing or retarding the dark oxidations of MAA and MMA in a natural environment is to chemically decorate or protect the C-H bond in the methyl connected to the C=C bond. The present results are expected to provide a general guide for understanding the dark oxidation mechanism of organic compounds and polymers.     

Phenanthrene-fused azo-ene-ynes: synthesis of dibenzo[f,h]cinnoline and dibenzo[e,g]isoindazole derivatives

The cyclization reactions of a phenanthreno-fused azo-ene-yne compound have been studied both experimentally and computationally. Experimental results show that this system is prone to dimerization, more so than previously studied naphthalene- and benzene-based analogues. Calculations reveal that pyrazoles and arene-fused pyrazoles strongly stabilize carbenes in the 5-position through "coarctate conjugation", suggesting a stationary concentration of the carbenes/carbenoids during cyclization that is high enough for dimerization.     

Nucleophilic substitution at phosphorus: stereochemistry and mechanisms

This review is devoted to the stereochemistry of nucleophilic substitution reactions at phosphorus. The study of the reactions of phosphoryl group transfer is important for biological and molecular chemistry. The stereochemistry and mechanisms of S_N1(P) monomolecular and S_N2(P) bimolecular nucleophilic substitution reactions of organophosphorus compounds are discussed. It has been shown that hydrolysis of many natural phosphates proceeds according to the monomolecular S_N1(P) mechanism via the formation of metaphosphate intermediate (PO₃^?). S_N2(P) nucleophilic substitution at chiral trivalent or pentavalent phosphorus compounds proceeds via the formation of penta-coordinated transition state or pentacoordinate intermediate.     

Mechanism of the S-->N isomerization and aquation of the thiocyanato pentaammine cobalt(III) ion

All of the stationary points on the potential energy surface of the S-->N isomerization and aquation of the Co(NH3)5SCN2+ ion have been investigated with ab initio quantum chemical methods. Also the corresponding anations of the Co(NH3)5OH2(3+) ion by the N and S ends of SCN- and the substitution of thiocyanate via the D mechanism have been studied. All calculations have been performed by taking into account hydration. The most favorable reaction of Co(NH3)5SCN2+ is the isomerization. It is concerted, follows the I or Id mechanism, depending on the applied criteria, and proceeds via a T-shaped transition state. The aquations of Co(NH3)5SCN2+ and Co-(NH3)5NCS2+ and the corresponding inverse reactions, the anations, all proceed via the Id mechanism. The activation energies, calculated for the isomerization and aquation, agree with experiment, and so does the difference of the activation energies for the anations by the two donors of SCN-. This energy difference reflects the disparate nucleophilicities of the N and S ends of SCN- and shows that bond making in the transition state is significant for the Id mechanism. Isomerization and aquation are two parallel reactions which proceed via two disparate transition states. The computed activation energy for the SCN- substitution via the D mechanism is the highest, and therefore, this pathway is unlikely to operate for the isomerization and aquation of Co(NH3)5SCN2+. The S-->N isomerization and the SCN- substitution via the D mechanism were furthermore computed for the free ions in the gas phase: the isomerization would require a higher activation energy and follow the Ia mechanism. The activation energy for the SCN- substitution via the D mechanism would be very high, because of the large electrostatic work which is required for the removal of an anion from a (formally) 3+ charged cation.     

Stereoselective synthesis of cis- or trans-3,5-disubstituted pyrazolidines via Pd-catalyzed carboamination reactions: use of allylic strain to control product stereochemistry through N-substituent manipulation

The stereoselective synthesis of either trans- or cis-3,5-disubstituted pyrazolidines is accomplished via Pd-catalyzed carboamination reactions of unsaturated hydrazine derivatives. The products are obtained in good yield with up to >20:1 diastereoselectivity. Stereocontrol is achieved by modulating the degree of allylic strain in the transition state for syn-aminopalladation through a simple modification of the substrate N(2)-substituent. The pyrazolidine products can be further transformed to 3,5-disubstituted pyrazolines via deprotection/oxidation, or to substituted 1,3-diamines via N-N bond cleavage.