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.     

Theoretical studies on the electrocyclic reactions of bis(allene) and vinylallene. Role of allene group

The reaction mechanisms of the electrocyclic ring closure of bis(allene) and vinylallene were studied by ab initio MO methods. The conrotatory and disrotatory pathways of the electrocyclic reactions from bis(allene) to bis(methylene)cyclobutene were determined by a CASSCF method. The transition state on the conrotatory pathway is 26.8 kcal/mol above bis(allene) and about 23 kcal/mol lower than that on the disrotatory pathway at a MRMP calculation level. The activation energy on the conrotatory pathway is lower by 23 kcal/mol than that of the electrocyclic reaction of butadiene. This lower energy barrier comes from the interactions of the "side pi orbitals" of the allene group. The interaction of the "vertical pi orbitals" of the allene group is predominant at the early stage of the reaction. The activation energy of the electrocyclic reaction of vinylallene is about 8.5 kcal/mol higher than that on the conrotatory pathway of bis(allene).     

Conrotatory ring-opening reactions of cyclopropyl anions in monocyclic and tricyclic systems

[reaction: see text] Only conrotatory transition structures were located by B3LYP6-311++G(3df, 2p) computations for the electrocyclic ring opening of cyclopropyl anions having different substituents (H, Me, CN). The transition structure for the similarly substituted cyclopropyl anion fused to a bicyclic system exhibits the same features, in apparent contradiction with the observed product. A reaction path where the direction of twist changes after the transition state provides an explanation alternative to those proposed in recent reports.     

Substituent Effects on Rates and Stereoselectivities of Conrotatory Electrocyclic Reactions of Cyclobutenes. A Theoretical Study

Substituent effects on the geometries and conrotatory electrocyclic ring openings of cyclobutenes were studied. This work extends the original investigations to many more substituents and provides a comprehensive theory of substituent effects on geometries and reaction rates. The effects of substitution at the 1 position are minimal; donor substituents raise the activation energy slightly, and powerful acceptor substituents slightly lower the activation energy. Substituents on C(3) cause small distortions of the cyclobutene geometry, in the same direction as the favored stereochemistry of reaction. Donors prefer outward rotation, while strong acceptors prefer inward rotation. The activation energy changes and cyclobutene geometrical perturbations were found to correlate with Taft sigma(R)(0) parameters. Amino, hydroxy, fluoro, chloro, methyl, cyano, formyl, and vinyl substituents were studied in the 1 position. Boryl, dimethylboryl, nitroso, formyl, nitro, carboxyl (neutral, protonated, and deprotonated), cyano, trifluoromethyl, sulfoxyl, sulfonyl, sulfinic acid, imino, N-protonated imino, ammonio, ethynyl, methyl, mercapto, chloro, fluoro, hydroxyl, amino, lithium oxy, vinyl, and acetyl were calculated as substituents in the 3 position. Comparisons with experimental results are given when available, and predictions are made in other cases.     

On the mechanism of conversion of N-acyl-4-acyloxy-beta-lactams into 2-substituted 1,3-oxazin-6-ones. Can a low-barrier transition state be antiaromatic?

The mechanism of the conversion of N-acyl-4-acyloxy-beta-lactams into 1,3-oxazin-6-ones has been investigated using ab initio and density functional theories. It has been found that two pseudopericyclic reactions are involved in the whole process. The first key reaction is a retro-[4-exo-dig] cyclization instead of a thermal conrotatory electrocyclic ring opening. Magnetic characterization of the corresponding transition structure shows antiaromatic character, despite the low activation energy associated with this process. The second step is very exothermic and has no activation barrier. It corresponds to another pseudopericyclic reaction instead of a six-electron disrotatory electrocyclization. These results confirm that there is no correlation between aromaticity and pseudopericyclic reactions. In contrast, thermal-symmetry-allowed pericyclic reactions are always aromatic. Therefore, magnetic analysis of the corresponding transition structures constitutes a useful tool to distinguish between both kinds of processes.     

An orbital phase theory for the torquoselectivity of the ring-opening reactions of 3-substituted cyclobutenes: geminal bond participation

We apply an orbital phase theory to the torquoselectivity of the electrocyclic reactions of 3-substituted (X) cyclobutenes. The torquoselectivity is shown to be controlled by the orbital-phase relation of the reacting pi(CC) and sigma(CC) bonds with the sigma(CX) bond geminal to the sigma(CC) bond to be cleaved. The inward rotation of electron-donating sigma(CX) bonds and outward rotation of electron-withdrawing sigma(CX) bonds have been deduced from the orbital-phase theory. Enhancement of the inward rotation by the electron-donating capability of the sigma(CX) bonds is confirmed by the correlation between the torquoselectivity and sigma(CX) orbital energy. The orbital overlaps between the geminal sigma(CX) (sigma(CH)) and sigma(CC) bonds are found to be important as well. Unsaturated substituents with low-lying unoccupied pi orbitals also promote the inward rotation.     

Origins of inward torquoselectivity by silyl groups and other sigma-acceptors in electrocyclic reactions of cyclobutenes

Recent reports of inward torquoselectivities in thermal electrocyclic ring-opening reactions of 3-silylcyclobutenes have revealed that saturated silyl substituents, just like the extensively studied pi-acceptors, can exert contrasteric effects. The origins of torquoselectivity for substituents lacking pi orbitals have been explained using B3LYP density functional calculations. Orbital interactions involving the substituent vacant orbitals and the occupied orbitals associated with the breaking bonds are found to control these contrasteric torquoselectivities, with minor contributions from electrostatic effects. Reaction energetics and transition states for electrocyclic ring-opening reactions of 3-silyl, fluorosilyl, difluorosilyl, trifluorosilyl, methylsilyl, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, ammonio, phosphonio, formyl, and borohydrido cyclobutenes are reported to complement previous extensive studies of unsaturated substituents. Inward stereoselectivities are predicted for various silyl and phosphonium substituents, along with potent pi-acceptors studied earlier. Cope and Diels-Alder reactions involving silyl substituents are also computed.     

Computational and Experimental Evidence of Two Competing Thermal Electrocyclization Pathways for Vinylheptafulvene

The thermal electrocyclic ring‐closure reaction of vinylheptafulvene (VHF) to form dihydroazulene (DHA) is elucidated herein by using DFT and ¹H NMR spectroscopy. Two different transition states were found computationally; one corresponds to a disrotatory pathway, which is allowed according to the Woodward–Hoffmann selection rules, whereas the other corresponds to a conrotatory pathway. The conrotatory pathway is found to be zwitterionic in the transition state, whereas the disrotatory transition state varies in zwitterionic character depending on solvent and substituents in the molecular framework. The conrotatory and disrotatory transition states are found to have similar energy and their relative stability varies with solvent polarity and functionalization at the C1 position. To support these findings, we chemically ring‐opened diastereomerically pure 1‐(benzothiazol‐2‐yl)‐DHA to give the VHF form, then subsequently thermally reconverted the VHF to DHA in a range of solvents with various polarities. We found that, depending on solvent polarity, different ratios of anti‐ and syn‐diastereoisomers of DHA were formed in a systematic manner, which supports the existence of two distinct thermal ring‐closure pathways for VHF.     

Reduced classical trajectory equations for electronically non-adiabatic transition on photochemical pericyclic reactions

It may be difficult to use the classical trajectory equations (CTE) for the estimation of electronically non-adiabatic transition probabilities in photochemical pericyclic reactions because of many nuclear degrees of freedom. In order to avoid this difficulty, the CTE were reformulated in terms of the reaction path coordinates, and the reduced CTE were derived, in which the system was restricted to move one-dimensionally along the postulated reaction path. As an application, the non-adiabatic decay from the lowest excited state to the ground state was investigated for the conrotatory and disrotatory processes of the photochemical electrocyclic reaction of 1,3-cis-butadiene to form cyclobutene.     

A theoretical study of cyclohexyne addition to carbonyl-Cα bonds: allowed and forbidden electrocyclic and nonpericyclic ring-openings of strained cyclobutenes

The mechanism of cyclohexyne insertion into a C(O)-C(α) bond of cyclic ketones, explored experimentally by the Carreira group, has been investigated using density functional theory. B3LYP and M06-2X calculations were performed in both gas phase and THF (CPCM, UAKS radii). The reaction proceeds through a stepwise [2 + 2] cycloaddition of cyclohexyne to the enolate, followed by three disparate ring-opening possibilities of the cyclobutene alkoxide to give the product: (1) thermally allowed conrotatory electrocyclic ring-opening, (2) thermally forbidden disrotatory electrocyclic ring-opening, or (3) nonpericyclic C-C bond cleavage. Our computational results for the model alkoxide and potassium alkoxide systems show that the thermally allowed electrocyclic ring-opening pathway is favored by less than 1 kcal/mol. In more complex systems containing a potassium alkoxide (e-f), the barrier of the allowed conrotatory ring-opening is disfavored by 4-8 kcal/mol. This suggests that the thermodynamically more stable disrotatory product can be formed directly through a "forbidden" pathway. Analysis of geometrical parameters and atomic charges throughout the ring-opening pathways provides evidence for a nonpericyclic C-C bond cleavage, rather than a thermally forbidden disrotatory ring-opening. A true forbidden disrotatory ring-opening transition structure was computed for the cyclobutene alcohol; however, it was 19 kcal/mol higher in energy than the allowed conrotatory transition structure. An alternate mechanism in which the disrotatory product forms via isomerization of the conrotatory product was also explored for the alkoxide and potassium alkoxide systems.     

Ab initio study of the pathways and barriers of tricyclo[4.1.0.0(2,7)]heptene isomerization

The thermal isomerization of tricyclo[4.1.0.0(2,7)]heptene has been studied using computational chemistry with structures determined at the MCSCF level and energies at the MRMP2 level. Both the allowed conrotatory and forbidden disrotatory pathways have been elucidated resulting in cycloheptatriene isomers. Four reaction channels are available for the conrotatory pathway depending on which bond breaks first in the bicyclobutane moiety leading to enantiomeric pairs of (E,Z,Z)-1,3,5-cycloheptatriene and (Z,E,Z)-1,3,5-cycloheptatriene intermediates. The activation barrier is calculated to be 31.3 kcal·mol?1 for two channels and 37.5 kcal·mol?1 for the other two. The lower activation barrier leading to the (E,Z,Z)-1,3,5-cycloheptatriene enantiomeric pair is proposed to be due to resonance within the transition state. The same behavior was observed for the disrotatory pathway with activation barriers of 42.0 kcal·mol?1 and 55.1 kcal·mol?1 for the two channels, again with one transition state resonance stabilized. The barriers for trans double bond rotation of the intermediate cycloheptatrienes are determined to be 17.1 and 17.4 kcal·mol?1, about 5 kcal·mol?1 more than that for the seven carbon diene (E,Z)-1,3-cycloheptadiene. The electrocyclic ring closure of the trans cycloheptatrienes have been modeled and barriers determined to be 11.1 and 11.9 kcal·mol?1 for the formation of bicyclo[3.2.0]hepta-2,6-diene. This structure was previously reported as the end product for thermolysis of the parent tricyclo[4.1.0.0(2,7)]heptene. The thermodynamically more stable cycloheptatriene can be formed from bicyclo[3.2.0]hepta-2,6-diene through a two step process with a calculated pseudo first-order barrier of 36.4 kcal·mol?1. The trans-cycloheptatrienes reported herein are the first characterization of a small seven-membered ring triene with a trans double bond.     

Hyperconjugative effects in the stereoselective ring-opening reactions of oxetenoxides

[reaction: see text] Unexpectedly, the pattern of the stereoselectivity in the ring-opening reactions of lithium oxetenoxides is not consistent with the bulkiness of substituents, and both the bulkier tert-butyl and silyl substituents favor inward rotation. With the aid of B3LYP calculations, the hyperconjugative interaction between the breaking C(1)-O sigma and its anti-periplanar Z-Me (Z = Si or C) sigma orbital is found to be responsible among the secondary orbital interactions of the substituents and the oxetene moiety.     

Criteria for pericyclic and pseudopericyclic character of electrocyclization of (Z)-1,2,4,6-heptatetraene and (2Z)-2,4,5-hexatriene-1-imine

The electrocyclic reaction mechanisms of (Z)-1,2,4,6-heptatetraene and (2Z)-2,4,5-hexatriene-1-imine were studied by ab initio MO methods. The activation energy barrier height of the electrocyclic reaction of (Z)-1,2,4,6-heptatetraene is extremely a low energy barrier of 8.58 kcal/mol by a MRMP method. The activation energy barrier height of the electrocyclic ring closure of the trans-type of (2Z)-2,4,5-hexatriene-1-imine is lower by 3.18 kcal/mol than that of (Z)-1,2,4,6-heptatetraene. These low energy barriers come from some orbital interactions relating to allene group. For the reaction of (Z)-1,2,4,6-heptatetraene, the interactions of the vertical and side π orbitals of the allene group with another terminal π orbital are important at the transition state. The interaction of the vertical π orbital of allene group with a lone pair orbital of N atom is dominant at the transition state of the reaction of the trans-type of (2Z)-2,4,5- hexatriene-1-imine. The electrocyclic mechanism of the cis-type of (2Z)-2,4,5-hexatriene-1-imine was also discussed. Contribution of the Mark S. Gordon 65th Birthday Festschrift issue.     

Electrocyclic ring opening of cis-bicyclo[m.n.0]alkenes: the anti-Woodward-Hoffmann quest

The dubbed anti-Woodward-Hoffmann ring-opening reaction of cis-bicyclo[4.2.0]oct-7-ene to yield cis,cis-cycloocta-1,3-diene has been intensively studied with robust, high-level computational methods. This reaction has been found to proceed through a conrotatory allowed pathway to afford cis,trans-cycloocta-1,3-diene followed by E to Z isomerization, instead of a disrotatory forbidden pathway, as suggested. Computational calculations of kinetic isotope effects are consistent with this interpretation and the experimental values. The study of lower bicyclic homologues with [3.2.0], [2.2.0] and [2.1.0] skeletons indicates the feasibility of a mechanistic change towards the anti-Woodward-Hoffmann disrotatory path. This is clearly favored for the ring opening of the highly strained cis-bicyclo[2.1.0]pent-2-ene and is highly competitive with the conrotatory path for cis-bicyclo[2.2.0]hex-2-ene. Therefore, the rearrangement of the smallest bicyclic cyclobutene is predicted computationally to be an anti-Woodward-Hoffmann disrotatory electrocyclic ring-opening reaction.     

Thermal isomerization of tricyclo[4.1.0.0(2,7)]heptane and bicyclo[3.2.0]hept-6-ene through the (E,Z)-1,3-cycloheptadiene intermediate

The thermal isomerization of tricyclo[4.1.0.0(2,7)]heptane and bicyclo[3.2.0]hept-6-ene was studied using ab initio methods at the multiconfiguration self-consistent field level. The lowest-energy pathway for thermolysis of both structures proceeds through the (E,Z)-1,3-cycloheptadiene intermediate. Ten transition states were located, which connect these three structures to the final product, (Z,Z)-1,3-cycloheptadiene. Three reaction channels were investigated, which included the conrotatory and disrotatory ring opening of tricyclo[4.1.0.0(2,7)]heptane and bicyclo[3.2.0]hept-6-ene and trans double bond rotation of (E,Z)-1,3-cycloheptadiene. The activation barrier for the conrotatory ring opening of tricyclo[4.1.0.0(2,7)]heptane to (E,Z)-1,3-cycloheptadiene was found to be 40 kcal mol(-1), while the disrotatory pathway to (Z,Z)-1,3-cyclohetpadiene was calculated to be 55 kcal mol(-1). The thermolysis of bicyclo[3.2.0]hept-6-ene via a conrotatory pathway to (E,Z)-1,3-cycloheptadiene had a 35 kcal mol(-1) barrier, while the disrotatory pathway to (Z,Z)-1,3-cyclohetpadiene had a barrier of 48 kcal mol(-1). The barrier for the isomerization of (E,Z)-1,3-cycloheptadiene to bicyclo[3.2.0]hept-6-ene was found to be 12 kcal mol(-1), while that directly to (Z,Z)-1,3-cycloheptadiene was 20 kcal mol(-1).     

Theoretical study of the electrocyclic ring closure of hydroxypentadienyl cations

At the 6-311G* level of theory, DFT methods predict that the rearrangement of 1,4-dihydroxy-5-methylpentadienyl cation 1 (R = Me) to protonated trans-3-hydroxy-2-methylcyclopent-4-en-1-one 2, an intermediate step in the Piancatelli reaction or rearrangement of furfuryl carbinols to trans-2-alkyl(aryl)-3-hydroxycyclopent-4-en-1-one, is a concerted electrocyclic process. Energetic, magnetic, and stereochemical criteria are consistent with a conrotatory electrocyclic ring closure of the most stable out,out-1 isomer to afford trans-2. Although the out,in-1 isomer is thermodynamically destabilized by 6.84 kcal mol(-1), the activation energy for its cyclization is slightly lower (5.29 kcal mol(-1) versus 5.95 kcal mol(-1)). The cyclization of the isomers of 1 with the C1-hydroxy group inwards showed considerably higher activation energies than their outwards counterparts. in,out-1, although close in energy to out,out-1 (difference of 1.57 kcal mol(-1)) required about 10 kcal mol(-1) more to reach the corresponding transition structure. The value measured for the activation energy of in,in-1 (17.32 kcal mol(-1)) eliminates the alternative conrotatory electrocyclization of this isomer to provide trans-2. Geometric scrambling by isomerization of the terminal C1--C2 bond of 1 is also unlikely to compete with electrocyclization. The possibility to interpret the 1-->2 reaction as a nonpericyclic cationic cyclization was also examined through NBO analysis, and the study of bond lengths and atomic charges. It was found that the 1-->2 concerted rearrangement benefits from charge separation at the cyclization termini, an effect not observed in related concerted electrocyclic processes, such as the classical Nazarov reaction 3-->4 or the cyclization of the isomeric 2-hydroxypentadienyl cation 5.     

Transannular cyclizations of zerumbone epoxide

Formic acid catalyzed rearrangement of zerumbone epoxide 3 gives three major bicyclic products, 4–6. The most important rearrangement is conrotatory electrocyclic Nazarow reaction. The structures were deduced from spectral and chemical evidence. ¹³C NMR are presented. An X-ray study has independently confirmed the proposed structures.     

Ring-closure reactions of 1,2-diaza-4,5-benzoheptatrienyl metal compounds: experiment and theory

2-Alkenylbenzylidene hydrazones 5a-m, which are accessible in good to excellent yields in a four-step synthesis, are converted into 1,2-diaza-4,5-benzoheptatrienyl metal compounds 1a-m by treatment with KO-t-Bu as base. These metal compounds undergo the various types of reactions in good yields and exclusively depending on the nature of substituents R(1) and R(3). Thus, metal compounds 1a-c carrying alkyl substituents R(1) and R(3) form 3H-benzodiazepines 6a-c after electrophilic quench of the intermediate cyclic anion 7 in a 7-endo-trig electrocyclic reaction with a mo?bius aromatic transition structure 1(-)-TS. Similarly, a benzothienyl derivative 5n is converted into diazepine 6d. Potassium compounds 1d-h, which are N-methyl and aryl substituted at R(3), form 1,2-dihydrophthalazines 8a-e in a predominantly charge-controlled 6-exo-trig cyclization reaction. In contrast, aryl-aryl-substituted systems 5i-m did not lead to cyclic products upon deprotonation, but the intermediate open-chain metal compounds 1i-m were trapped by acid chlorides at N1 to yield the hydrazides 10a-e. We interpret thermodynamics and kinetics of these reactions in the context of the Baldwin rules on the basis of quantum chemical calculations and discuss the transition structures considering the results of NICS and NBO-charge calculations. Examples of the products 6, 8, and 10 could be characterized by X-ray diffraction.     

Pyrolysis and UV photoelectron spectroscopy of bicyclo[3.2.0]hept-6-en-2-one; preparation and detection of cyclohepta-2(Z),4(E)-dien-1-one

Flash vacuum pyrolysis of bicyclo[3.2.0]hept-6-en-2-one (1) in the source chamber of a UV photoelectron (PE) spectrometer using a CW CO2 laser as a directed heat source facilitated an electrocyclic ring expansion to yield the transient species cyclohepta-2(Z),4(E)-dien-1-one (2), the PE spectrum of which was compared to that of an authentic sample of cyclohepta-2(Z),4(Z)-dien-1-one (4) and confirmed a conrotatory ring opening of 1 that obeys the Woodward-Hoffmann rules.     

Experimental and computational study of the conrotatory ring opening of various 3-chloro-2-azetines

A combined experimental and theoretical study is presented on 2-azetines, a class of azaheterocyclic compounds, which are difficult to access but have shown a unique reactivity as strained cyclic enamines. New highly substituted 2-azetines bearing aryl substituents at the 2- and 4-position were synthesized from 3,3-dichloroazetidines. Whereas 2-aryl-3,3-dichloroazetidines gave stable 2-aryl-3-chloro-2-azetines upon treatment with sodium hydride in DMSO, 2,4-diaryl-3,3-dichloroazetidines showed a remarkably different reactivity in that they afforded benzimidoyl-substituted alkynes under similar mild treatment with base. The formation of the alkynes involves electrocyclic ring opening of intermediate 2,4-diaryl-3-chloro-2-azetines and elimination of hydrogen chloride. Ab initio theoretical calculations confirmed the experimental findings and demonstrated that the 4-aryl substituent is responsible for this remarkably enhanced reactivity of 2-azetines toward electrocyclic conrotatory ring opening by a significant decrease in reaction barrier of about 30 kJ/mol. This activation effect by an aryl group in the allylic position toward electrocyclic ring opening of unsaturated four-membered rings is of general importance since a similar increased reactivity of 4-aryloxetes, 4-arylthiete-1,1-dioxides, and 3-arylcyclobutenes has been reported in literature as well.