Conrotatory Ring Opening Research Articles

Origin of a Kinetically Selective Route for Thermoreversible Valence Tautomerism-Based Photoswitching in O-Heterocycles Containing Conjugated Dienes.

The thermal electrocyclic ring opening of fused cis-cyclobutene to cis,cis-diene is prohibited according to the Woodward-Hoffmann (WH) rules; nonetheless, experiments provide firm evidence for their formation. However, the mechanism, electronic structure, and behavior during the reaction are ambiguous. Herein, we attempt to gain insights into the mechanism of thermal ring opening in four O-heterocycles containing a conjugated diene as the core skeleton. The results emphasize that the reaction initiates with a conrotatory ring opening to produce a cis,trans-diene as a strained transient intermediate following the WH rules but ultimately leads to a forbidden product. The conversion of cis,trans-diene to cis,cis-diene is kinetically preferred through double-bond rotation, involving the formation of a singlet biradicaloid. The expected H-shift is unfavorable because the requirement of suprafacial H transfer incorporates additional strain, while the transfer of other available H is symmetry-forbidden. The increased electrophilicity at O promotes C-O dissociation in the 8-membered cyclic cis,trans-dienes with fused benzene. This enables thermoreversible photoswitching via a two-step mechanism and kinetically refutes the direct disrotatory pathway. These systems can outperform energy storage, and critical insight into their mechanism with the aid of comprehensive electronic structure analysis would assist in their rational design in the future.

Pulling Outward but Reacting Inward: Mechanically Induced Symmetry-Allowed Reactions of cis- and trans-Diester-Substituted Dichlorocyclopropanes

AbstractThe mechanically induced symmetry-allowed disrotatory ring openings of cis- and trans-gem-dichlorocyclopropane (gDCC) diesters are demonstrated through sonication and single-molecule force spectroscopy (SMFS) studies. In contrast to the previously reported symmetry-forbidden conrotatory ring opening of alkyl-tethered trans-gDCC, we show that the diester-tethered trans-gDCC primarily undergoes a symmetry-allowed disrotatory pathway even at the high forces (>2 nN) and short-time scales (ms or less) of sonication and SMFS experiments. The quantitative force-rate data obtained from SMFS data is consistent with computational models of transition-state geometry for the symmetry-allowed process, and activation lengths of 1.41 ± 0.02 Å and 1.08 ± 0.03 Å are inferred for the cis-gDCC diester and trans-gDCC diester, respectively. The strong mechanochemical coupling in the trans-gDCC is notable, given that the directionality of the applied force may appear initially to oppose the disrotatory motion associated with the reaction. The stereochemical perturbations of mechanical coupling created by the ester attachments reinforce the complexity that is possible in covalent polymer mechanochemistry and illustrate the breadth of reactivity outcomes that are available through judicious mechanophore design.

A Short, Efficient, and Stereoselective Synthesis of Piperine and its Analogues

A quantitative synthesis of piperine from commercially available starting material is presented. The synthesis relies on a stereoselective nucleophilic attack of an in situ generated cuprate onto a cyclobutene lactone. The so-formed aryl-substituted cyclobutene spontaneously undergoes a conrotatory 4π-electrocyclic ring opening to form the 4-aryl pentadienoic acid as a single diastereoisomer. The high-yielding synthesis can be easily modulated on the aryl and on the amide moiety for the synthesis of a wide range of piperine analogues.

Intermolecular [2 + 2] Cycloaddition/Isomerization of Allenyl Imides and Unactivated Imines for the Synthesis of 1-Azadienes Catalyzed by a Ni(ClO4)2·6H2O Lewis Acid

The intermolecular [2 + 2] cycloaddition/isomerization between allenyl imides and N-(2-methoxyphenyl) aldimine counterparts catalyzed by a Ni(ClO4)2·6H2O Lewis acid at room temperature was discovered, providing a facile access to 1-azadiene derivatives with high atom economy. The incorporation of an 2-oxazolidinone group into allene amides resulted in unusual reactivity for the imine-metathesis and synthetic application to a chiral γ,δ-unsaturated β-ketoimide. A mechanistic experiment using density functional theory (DFT) computation in CH2Cl2 with the B3LYP functional rationalized the proposed catalytic pathway involving initial stepwise [2 + 2] cycloaddition to provide an azetidine species, two-time proton transfer to form a 2-azetine intermediate, and final conrotatory ring opening for trans-1-azadiene-based substances.

Force-Induced Catastrophes on Energy Landscapes: Mechanochemical Manipulation of Downhill and Uphill Bifurcations Explains the Ring-Opening Selectivity of Cyclopropanes.

The mechanochemistry of ring-opening reactions of cyclopropane derivatives turns out to be unexpectedly rich and puzzling. After showing that a rare so-called uphill bifurcation in the case of trans-gem-difluorocyclopropane turns into a downhill bifurcation upon substitution of fluorine by chlorine, bromine, and iodine in the thermal activation limit, the dichloro derivative is studied systematically in the realm of mechanochemical activation. Detailed exploration of the force-transformed potential energy surface of trans-gem-dichlorocyclopropane in terms of Dijkstra path analysis unveils a hitherto unknown topological catastrophe where the global shape of the energy landscape is fundamentally changed. From thermal activation up to moderately large forces, it is an uphill bifurcation that decides about dis- versus conrotatory ring-opening followed by separate transition states along both pathways. Above a critical force, the two distinct transition states merge to yield a single transition state such that the decision about the dis- versus conrotatory ring-opening process is taken at a newly established downhill bifurcation. The discovery of a force-induced qualitative change of the topology of a reaction network vastly transcends the previous understanding of the ring-opening reaction of this species. It would be astonishing to not discover a wealth of such catastrophes for mechanochemically activated reactions, which will greatly extend the known opportunities to manipulate chemical reaction networks.

Lumisterol to Tachysterol Photoisomerization in EPA Glass at 77 K. A Comparative Study

We present a comparative study of the photoisomerizations of lumisterol (Lumi), previtamin (Pre), and provitamin D3 (Pro) to tachysterol (Tachy) at 77 K in EPA (5:5:2 ether, isopentane, and ethanol by volume) glass. Fluorescence, fluorescence excitation, and UV spectra, measured in the course of these reactions, were analyzed using singular value decomposition with self-modeling (SVD-SM). This represents an extension of previous work that led to the conclusion that in the EPA glass Pre exists as an s-cis,s-cis-conformer (cZc-Pre) which gives, exclusively, an unstable s-cis,s-cis-conformer of Tachy (cEc-Tachy) and Pro gives mainly the tEc-Tachy, that corresponds to a stable s-trans,s-cis-conformer. ( Redwood , C. ; et al. J. Phys. Chem. Lett. 2013 , 4 , 716 - 721 . ) The surprising result was that the major Pre photoproduct from Pro also has a tZc-Pre conformation instead of the expected cZc-Pre conformation. Accordingly, the Pre to Tachy cis-trans photoisomerization proceeds via a conformer specific one-bond-twist (OBT) process as proposed by Havinga ( Maessen , P. A. ; et al. Angew. Chem. Int. Ed. Engl. 1983 , 22 , 718 - 719 . Maessen , P. A. ; et al. Angew. Chem. Int. Ed. Engl. 1983 , 22 , 994 - 1004 . Maessen , P. A. Ph.D. Thesis, State University at Leiden, Leiden, The Netherlands, 1983. ). The role of the EPA glass in controlling conformer distributions and reaction outcomes is further explored by the extension of the studies to Lumi, whose structure differs substantially from that of its stereoisomer, Pro. Initially, the light-induced conrotatory ring openings of Pro and Lumi are expected to give cZc-Pre conformers that differ in the relative orientation of the double bond dihedral angles that define the chiral axis of the triene moiety: (-)cZ(-)c-Pre and (+)cZ(+)c-Pre, respectively. In the case of Pro, much of the cZc-Pre proceeds to tZc-Pre, the precursor of tEc-Tachy. In contrast, we show that under the same conditions most cZc-Pre formed from Lumi retains the cZc-conformation and isomerizes to cEc-Tachy. cZc-Pre from Lumi was not detected by fluorescence, but UV absorption measurements establish its formation as an essential intermediate to Tachy. Aided by theoretical calculations of conformer UV and CD spectra, we conclude that fluorescent thermodynamic Pre and nonfluorescent Pre from Lumi are both (+)cZ(+)c-Pre conformers. They differ in the orientation of the OH in the A ring, pseudoequatorial in the former and pseudoaxial in the latter. The most likely major photochemical sequences starting from Pre and Lumi are (+)cZ(+)c-Pre-eq-OH → (+)cE(+)c-Tachy-eq-OH and Lumi → (+)cZ(+)c-Pre-ax-OH → (+)cE(+)c-Tachy-eq-OH.

Comment on "trans-1,2-Disiloxybenzocyclobutene, an adequate partner for the auto-oxidation: EPR/spin trapping and theoretical studies" by J. Drujon et al., Phys. Chem. Chem. Phys., 2014, 16, 7513.

Despite the claim of the contrary, (i) the facile formation of a ring-opened cyclic peroxide from reaction of a 1,2-disubstituted benzocyclobutene with molecular oxygen has been reported before, and (ii) the analysis of the mechanistic steps of this process is incomplete, as only the symmetry-allowed conrotatory ring-opening of the benzocyclobutene has been considered. The probable involvement of biradical intermediates/biradicaloid transition states in a formally symmetry-forbidden reaction sequence has not been taken into account.

Intramolecular Photocycloaddition Reactions of Arylcyclopropane Tethered 1-Cyanonaphthalenes.

Intramolecular photocycloaddition reactions of 1-cyanonaphthalenes bearing an arylcyclopropane containing side chain were investigated. Photoreactions of members of this family in which the arylcyclopropane moiety is bonded at the 2-position of the 1-cyanonaphthalene ring produce head-to-head and head-to-tail 1,2-[3+2] photocycloadducts. On the other hand, substances in this family containing an arylcyclopropane side chain linked to the 4-position of the cyanoarene ring undergo photoreactions to form [4+3] photocycloadducts along with novel nine-membered ring products, which are produced by photochemically induced 10π conrotatory ring opening of the initially formed intramolecular [3+2] cycloadducts. The results of solvent effects and fluorescence investigations along with those focusing on corresponding intermolecular photoreactions demonstrate that the photocycloadducts are formed predominantly through an intramolecular exciplex mechanism and that a photoinduced intramolecular electron transfer pathway via zwitterionic biradicals might be partly responsible for the process when CH3CN is the solvent.

Combined Constant-Force and Constant-Velocity Single-Molecule Force Spectroscopy of the Conrotatory Ring Opening Reaction of Benzocyclobutene.

Single-molecule force spectroscopy (SMFS) of multi-mechanophore polymers has been used to provide kinetic and mechanistic insights into mechanochemical reactions. Whereas biological systems have benefitted from force clamp spectroscopy, synthetic polymers have been studied primarily with constant-velocity methods. Here, force clamp SMFS is applied to the mechanically accelerated conrotatory ring opening of benzocyclobutene, and a comparison with constant-velocity SMFS extends the range of available rate-versus-force data and corroborates the use of constant-velocity SMFS to extract force dependencies.

NBO analysis of the torquoselectivity of the electrocyclic reactions of mono-substituted cyclobutenes

Conrotatory ring opening of cyclobutene, 3-methoxycyclobutene, and 3-formylcyclobutene has been studied with the density functional theory. The stereoselectivity of these reactions has been elucidated on the basis of the natural bond orbital analysis and correlation diagrams. Hyperconjugative interactions substituent-cyclobutene occurring at the transition state seem to be responsible of these reactions' torquoselectivity.

Cyclohexadiene Revisited: A Time-Resolved Photoelectron Spectroscopy and ab Initio Study.

We have reinvestigated the excited state dynamics of cyclohexa-1,3-diene (CHD) with time-resolved photoelectron spectroscopy and fewest switches surface hopping molecular dynamics based on linear response time-dependent density functional theory after excitation to the lowest lying ππ* (1B) state. The combination of both theory and experiment revealed several new results: First, the dynamics progress on one single excited state surface. After an incubation time of 35 ± 10 fs on the excited state, the dynamics proceed to the ground state in an additional 60 ± 10 fs, either via a conrotatory ring-opening to hexatriene or back to the CHD ground state. Moreover, ring-opening predominantly occurs when the wavepacket crosses the region of strong nonadiabatic coupling with a positive velocity in the bond alternation coordinate. After 100 fs, trajectories remaining in the excited state must return to the CHD ground state. This extra time delay induces a revival of the photoelectron signal and is an experimental confirmation of the previously formulated model of two parallel reaction channels with distinct time constants. Finally, our simulations suggest that after the initially formed cis-Z-cis HT rotamer the trans-Z-trans isomer is formed, before the thermodynamical equilibrium of three possible rotamers is reached after 1 ps.

Competitive and Cooperative Torquoselectivity in the thermal ring opening of cyclobutene: A density functional insight

The competition between the two electron donors (–OCH 3 and –OSiH 3) have been studied by positioning them at geminal and vicinal locations. We have also studied the cis and trans geometrical isomerism at the vicinal location. Thermodynamic and activation parameters such as free energies have been computed to understand the potential energy surface of the reaction. Our computed activation hardness supports the proposed torquoselectivity. Further, Nucleus Independent Chemical Shift (NICS) was calculated at the ring centre of the transition state (TS) which additionally supports the torquoselectivity. The delicate preferences for the pathways have been substantiated through NBO interactions. Torquoselective preference for methoxy and silyloxy substituted cyclobutene during thermal conrotatory electrocyclic ring opening is substantiated through computational study at B3LYP/6-31G(d) level.

Substituent effects on rates and torquoselectivities of electrocyclic ring-openings of N-substituted 2-azetines.

Transition structures for the conrotatory electrocyclic ring-opening reactions of N-substituted 2-azetines were computed with the density functional M06-2X/6-31+G(d,p). A wide range of substituents from π acceptors (e.g., CHO, CN) to π donors (NMe2, OMe) was explored. Acceptor substituents delocalize the nitrogen lone pair and stabilize the reactant state of 2-azetines, while donors destabilize the 2-azetine reactant state. The conrotatory ring-opening is torquoselective, and the transition state for the outward rotation of the N-substituent and inward rotation of the nitrogen lone pair is preferred. This transition structure is stabilized by an interaction between the nitrogen lone pair and the vacant π* orbital. The activation free energies are linearly related to the reaction free energies and the Taft σR(0) parameter.

Reaction pathways by quantum Monte Carlo: insight on the torsion barrier of 1,3-butadiene, and the conrotatory ring opening of cyclobutene.

Quantum Monte Carlo (QMC) methods are used to investigate the intramolecular reaction pathways of 1,3-butadiene. The ground state geometries of the three conformers s-trans, s-cis, and gauche, as well as the cyclobutene structure are fully optimised at the variational Monte Carlo (VMC) level, obtaining an excellent agreement with the experimental results and other quantum chemistry high level calculations. Transition state geometries are also estimated at the VMC level for the s-trans to gauche torsion barrier of 1,3-butadiene and for the conrotatory ring opening of cyclobutene to the gauche-1,3-butadiene conformer. The energies of the conformers and the reaction barriers are calculated at both variational and diffusional Monte Carlo levels providing a precise picture of the potential energy surface of 1,3-butadiene and supporting one of the two model profiles recently obtained by Raman spectroscopy [Boopalachandran et al., J. Phys. Chem. A 115, 8920 (2011)]. Considering the good scaling of QMC techniques with the system's size, our results also demonstrate how variational Monte Carlo calculations can be applied in the future to properly investigate the reaction pathways of large and correlated molecular systems.

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.

Nonlocal Behavior of an Electron in the Ring-Opening of Cyclobutene

The nonlocal behavior of an electron in the ring-opening of cyclobutene is analyzed using the sharing amplitude and tools based thereupon. The sharing amplitude is a generalization of the absolute value squared of the wave function (a probability density according to the Born interpretation) to a measure that gives, for a single particle in a many particle system, both the relative phase of a wavelike quantity between any two space/spin points and a measure of the distribution of that quantity between those points. The sharing indices are related to the absolute value squared of the amplitude, thereby ensuring that the amplitude and the indices are consistent. To provide prototypical behavior of the sharing quantities in single and double bonds and to identify nonbonding and antibonding behavior, these tools are used to describe single electron behavior in ethane and ethylene, in the latter including separate σ and π contributions and two excited states. Similar analyses of the single and double carbon-carbon bonds in the reactant cyclobutene and in the product s-cis-butadiene (a planar transition state allowing for σ and π separation) are carried out. Comparisons are made to the prototypical molecules. The sharing quantities in the locally stable forms of s-gauche-butadiene are then considered. A remnant of the bond that is broken in cyclobutene is found in a form that is consistent with a conrotatory ring-opening, a behavior suggested by Woodward and Hoffmann on the basis of the symmetry of the highest occupied molecular orbital in the product, but here without appeal to only that molecular orbital. Finally, the nonlocal behavior of an electron during the breaking and making of bonds in the reaction is discussed for several geometries along the reaction path.

Quantum mechanical inspection of the Diels–Alder approach to biaryls mechanism

The Diels–Alder reaction of substituted cyclohexadienes with substituted phenylacetylenes offers an attractive alternative for the synthesis of biaryl compounds via a two-step cycloaddition/cycloelimination pathway. Quantum mechanical calculations using B3LYP and M06-2X density functional methods for the reaction of 2-chloro-6-nitrophenylacetylene with 1-carbomethoxy-cyclohexadiene show the reaction proceeds by a stepwise diradical [4+2] cycloaddition followed by concerted [2+4] cycloelimination of ethylene. [2+2] cycloadducts are also the result of stepwise addition. [2+2] cycloadducts isomerize to [4+2] cycloadducts via diradical pathways, which involve the same diradical intermediate in cycloaddition. There is also a competitive conrotatory ring opening followed by trans-cis double bond isomerization pathway of the [4.2.0] bicycle (the [2+2] cycloadduct) to give the cis,cis,cis-1,3,5-cyclooctatriene.

Thermal [2+3]‐Cycloadditions of trans‐1‐Methyl‐2,3‐diphenylaziridine with CS and CC Dipolarophiles: An Unexpected Course with Dimethyl Dicyanofumarate

AbstractThe thermal reaction of trans‐1‐methyl‐2,3‐diphenylaziridine (trans‐1a) with aromatic and cycloaliphatic thioketones 2 in boiling toluene yielded the corresponding cis‐2,4‐diphenyl‐1,3‐thiazolidines cis‐4 via conrotatory ring opening of trans‐1a and a concerted [2+3]‐cycloaddition of the intermediate (E,E)‐configured azomethine ylide 3a (Scheme 1). The analogous reaction of cis‐1a with dimethyl acetylenedicarboxylate (5) gave dimethyl trans‐2,5‐dihydro‐1‐methyl‐2,5‐diphenylpyrrole‐3,4‐dicarboxylate (trans‐6) in accord with orbital‐symmetry‐controlled reactions (Scheme 2). On the other hand, the reactions of cis‐1a and trans‐1a with dimethyl dicyanofumarate (7a), as well as that of cis‐1a and dimethyl dicyanomaleate (7b), led to mixtures of the same two stereoisomeric dimethyl 3,4‐dicyano‐1‐methyl‐2,5‐diphenylpyrrolidine‐3,4‐dicarboxylates 8a and 8b (Scheme 3). This result has to be explained via a stepwise reaction mechanism, in which the intermediate zwitterions 11a and 11b equilibrate (Scheme 6). In contrast, cis‐1,2,3‐triphenylaziridine (cis‐1b) and 7a gave only one stereoisomeric pyrrolidine‐3,4‐dicarboxylate 10, with the configuration expected on the basis of orbital‐symmetry control, i.e., via concerted reaction steps (Scheme 10). The configuration of 8a and 10, as well as that of a derivative of 8b, were established by X‐ray crystallography.

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.

ChemInform Abstract: Synthesis and Rearrangement of Dewar Benzenes into Biaryls: Experimental Evidence for Conrotatory Ring Opening.

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