Biradical Intermediates Research Articles

Extrapolating potential energy surfaces by scaling electron correlation: Isomerization of bicyclobutane to butadiene

The recently proposed potential energy surface (PES) extrapolation scheme, which predicts smooth molecular PESs corresponding to larger basis sets from the relatively inexpensive calculations using smaller basis sets by scaling electron correlation energies [A. J. C. Varandas and P. Piecuch, Chem. Phys. Lett. 430, 448 (2006)], is applied to the PESs associated with the conrotatory and disrotatory isomerization pathways of bicyclo[1.1.0]butane to buta-1,3-diene. The relevant electronic structure calculations are performed using the completely renormalized coupled-cluster method with singly and doubly excited clusters and a noniterative treatment of connected triply excited clusters, termed CR-CC(2,3), which is known to provide a highly accurate description of chemical reaction profiles involving biradical transition states and intermediates. A comparison with the explicit CR-CC(2,3) calculations using the large correlation-consistent basis set of the cc-pVQZ quality shows that the cc-pVQZ PESs obtained by the extrapolation from the smaller basis set calculations employing the cc-pVDZ and cc-pVTZ basis sets are practically identical, to within fractions of a millihartree, to the true cc-pVQZ PESs. It is also demonstrated that one can use a similar extrapolation procedure to accurately predict the complete basis set (CBS) limits of the calculated PESs from the results of smaller basis set calculations at a fraction of the effort required by the conventional pointwise CBS extrapolations.

The Reactivity of Calicheamicin γ1I in the Minor Groove of DNA: The Decisive Role of the Environment

Triggering and Bergman cyclization of calicheamicin gamma(1) (I) outside and inside the minor groove of the duplex 9mer-B-DNA sequence d(CACTCCTGG).d(CCAGGAGTG) were investigated by using density functional theory and molecular mechanics (DFT and MM) descriptions in which the ligand is completely described at the DFT and the receptor at the MM level. The calculated docking energy of calicheamicin gamma(1) (I) (-12.5 kcal mol(-1)) is close to the measured value of -9.7 kcal mol(-1) and the site specificity is in line with experimental observations. Calicheamicin is triggered in the minor groove in such a way that out of a cyclohexenone by Michael addition an E rather than a Z form of a cyclohexanone is formed, which in turn adopts a chair rather than a twistboat form. Decisive for the stereochemistry of the Michael addition is the orientation of the carbamate substituent at the headgroup of calicheamicin. Triggered calicheamicin can undergo the Bergman cyclization at body temperature only if present in its E chair form (activation enthalpy 16.4 kcal mol(-1)). An intermediate biradical is formed (docking energy -13.6 kcal mol(-1)), which has a sufficient lifetime to abstract two hydrogen atoms. Hydrogen abstraction is a two- rather than one-step process and involves the C5(H5') atom first and then the T22(H4') atom in line with experimental observations. The decisive role of using a DFT rather than an MM description for the ligand is documented.

Concerted and Stepwise Reaction Mechanisms for the Addition of Ozone to Acetylene: A Computational Study

The mechanism of the reaction between acetylene and ozone to form a primary ozonide (POZ) in the gas phase has been studied theoretically. The concerted pathway, HCCH + O3 --> POZ, proceeds via a biradicaloid transition state TS0. The stepwise pathway is a three-step reaction, HCCH + O3 --> M1 --> M2 --> POZ, involving two biradical TSs and two biradical intermediates M1 and M2. The segment of the global potential energy surface (PES) for the concerted pathway is characterized as a R-PES, which is obtained from the restricted (R) density functional theory and Hartree-Fock-based methods. The RDFT and RHF solutions of TS0 and O3 are unstable toward spin-symmetry breaking. The wave function instability for TS0 and O3 results in a discontinuity between the R-PES and the region of the global PES encompassing the biradical TSs and the intermediates of the stepwise pathway, which are characterized with unrestricted (U) methods. The global PES is characterized separately as an U(R)-PES using a combination of the R and U methods. Several different values of barriers for the concerted pathway and the energy of concert (Ec) can be estimated due to complications arising from the discontinuity between the R- and the U(R)-PES and the existence of two different RDFT and UDFT O3 equilibrium geometries. RCCSD(T)//RDFT predicts a barrier of 8.2 kcal/mol. U(R)CCSD(T)/U(R)DFT predicts a barrier of 13.8 kcal/mol for the concerted and 15.3 kcal/mol for the stepwise pathway. Comparison between the R-PES barrier to the concerted pathway and the U(R)-PES barrier to the stepwise pathway suggests the former to be the only significant mechanism. Consideration of the energy difference between TS1, the TS for the first step of the stepwise mechanism, and TS0 within the global PES leads to a significantly smaller Ec. Geometry optimization with CASSCF and energy point calculations with MRMP2 are employed to characterize TS0 and TS1. MRMP2//CASSCF predicts the energy level of TS1 to be higher than that of TS0 by 2 kcal/mol. Analysis of experimental and computational data based on the low estimate of Ec shows that the possibility of the stepwise pathway being a secondary channel at elevated temperatures cannot be ruled out.

Photochromism of phenoxynaphthacenequinones: diabatic or adiabatic phenyl group transfer

The photochromic reactions of 6-phenyloxy-5,12-naphthacenequinone (1) and of the 6,11-diphenyloxy derivative 2 were investigated by subpicosecond pump-probe, photoacoustic, and emission spectroscopies, and by nanosecond laser flash photolysis (LFP). The transformation of the trans-quinones 1 and 2 to their ana-isomers proceeds via short-lived triplet states of 1 and 2 (tau ca. 2 ns) and spiro-bridged biradical intermediates (ca. 6 ns). The long-lived (micros) ana-triplets that are observed by LFP of 1 and 2 are formed (predominantly) by reexcitation of the biradicals and ana-quinones, which appear during the laser pulse. The reverse reaction, ana-->trans, proceeds exclusively from the lowest pi,pi* singlet state of the ana-quinones.

Reaction of o-Benzyne with Tropothione Involving Biradical Processes

A benzyne-tropothione reaction was studied experimentally and computationally. Three isomeric products were detected by a careful experiment using two benzyne sources. The three equimolar products were identified. The expected symmetry-allowed [4+2] or [8+2] cycloadduct was not detected. In order to explain the unexpected products, density functional calculations and complete active space self-consistent field (CASSCF) calculations were carried out. The benzyne is, first, added to the tropothione via one-center C-S bond formation. Then a singlet biradical intermediate is formed. In the biradical, an alpha hydrogen atom of the tropothione moiety is moved to the benzyne moiety. A closed-shell intermediate is generated. This allene-type intermediate is isomerized to the second intermediate. The intramolecular proton shift in the latter leads to the three products. The biradical character of the benzyne has a key role in the present reaction and was discussed in reference to other benzyne reactions.

Exciting flavins: Absorption spectra and spin–orbit coupling in light–oxygen–voltage (LOV) domains

Flavins are central molecular chromophores for many photobiological processes. In this paper, several aspects of the photophysics and photochemistry of lumiflavin in a (protein) environment will be studied with the help of quantum chemical methods. In a first part of the paper, we present vertical singlet excitation energies for lumiflavin (a molecule of the isoalloxazin type), using time-dependent density functional theory (TD-DFT) in conjunction with the B3LYP hybrid functional. When calculated for isolated species, TD-DFT excitation energies are generally blue-shifted relative to the experimental absorption spectra of isoalloxazines in solution, or in a protein environment. We develop four different models to account for environmental effects, with special emphasis on the LOV1 domain of Chlamydomonas reinhardtii. It is found that the two lowest, allowed singlet excitations are sensitive to the polarizability of an environment, to hydrogen bonds, and to geometrical constraints imposed by the surrounding protein. All of this brings theory and experiment in better agreement. In the second part of the paper the light-induced adduct formation in LOV domains, between the chromophore and a neighbouring cystein unit is investigated. Energies along a model “reaction path” are calculated on the DFT/B3LYP and MCQDPT2 level of theories. A transition state for a H-transfer between the mercapto (SH–) group of cystein, and the N(5) position of flavin is found. The reaction requires spin–orbit coupling between the S 0 and the T 1 states of the system. Spin–orbit coupling constants between S 0 and T 1 are calculated, and found to be in the range of several tens of cm −1 after the transition state was passed. A biradical intermediate was observed along the reaction path.

Super Radical Stabilizers

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A silyl-mediated [3+2] photochemical cycloaddition

The generation of larger rings from intermediate cyclobutanes via a two-step [2+2] photocycloaddition – ring expansion, known as the de Mayo reaction, has been widely applied in synthesis. Herein a one-step synthesis of cyclopentanoids has been developed based on the photochemical irradiation of an enone in the presence of an allylsilane. The ability of the silyl moiety to stabilize the intermediate biradical is believed to be responsible for this unique transformation where one normally expects to see the [2+2] cyclobutane adduct.Key words: [2+2] photocycloaddition - ring expansion, allylsilanes, cyclopentanoids, photochemical.

Facile formation of acenaphtho[1,2- a]pyrene structures by thermal isomerization of bis(8-ethynyl-1-naphthyl)ethynes

The title 1,8-naphthylene–ethynylene compounds underwent thermal isomerization into acenaphtho[1,2- a]pyrene derivatives, and the structure of the new polycyclic aromatic system was established by X-ray analysis. The mechanism of the isomerization is explained in terms of sequential cyclization reactions via biradical intermediates followed by hydrogen migration.

Photolysis of Heptanal

Photolysis of heptanal is investigated from an experimental and theoretical point of view. Photoexcited heptanal is believed to undergo rapid intersystem crossing to the triplet manifold and from there undergoes internal H-abstraction to form biradical intermediates. The favored gamma-H abstraction pathway can cyclize or cleave to 1-pentene and hydroxyethene, which tautomerizes to acetaldehyde. Yields of 1-pentene and acetaldehyde were measured at 62 +/- 7% and 63 +/- 7%, respectively, relative to photolyzed heptanal. Additionally, small quantities of hexanal and hexanol were observed. On the basis of combined experimental and theoretical evidence, the remaining heptanal photolysis proceeds to form an estimated 10% HCO + hexyl radical and 30% cyclic alcohols, particularly 2-propyl cyclobutanol and 2-ethyl cyclopentanol.

Super Radical Stabilizers

A comprehensive series of substituted 1,1-dimethyl-2-methylenecyclopropanes have been thermally rearranged. These rearrangements proceed via singlet biradical intermediates that can be stabilized by substituents. Rates are greatly enhanced by certain groups that are termed super radical stabilizers. Substituents included 4-pyridyl N-oxide, 2-(1,6-methano[10]annulenyl), and a number of anion-substituted phenyl groups. Simple valence bond theory, as well as more sophisticated computational studies, gives insights into modes of radical stabilization.

Photocycloaddition of Cyclohex‐2‐enones to Penta‐1,2,4‐triene

AbstractDihydrothiinone 9a undergoes photocycloaddition regioselectively to all three CC bonds of penta‐1,2,4‐triene (10), the relative stabilities of the biradical intermediates determining the product distribution. In contrast, cyclohexenone 9b and dihydropyranone 9c afford more complex mixtures of bicyclo[4.2.0]octanones, which also turn out to be less stable on chromatographic workup, reflecting the higher strain due to the shorter bond lengths (CO and CC vs. CS) in the six‐membered rings, respectively.

Origin of regioselectivity in the intramolecular [2+2] photoreaction of α, β-unsaturated furanones to a terminal alkene

The intramolecular [2+2] photoreaction of α,β-unsaturated furanone to a terminal alkene presents a remarkable change in regioselectivity, with variation of the chain length of the terminal alkene. Head-to-tail (ht) regioselectivity was exclusively produced through one-carbon atom connection (furanone-1 n), whereas it was completely inverted when connection of two-carbon atoms takes place (furanone-2 n). The origin of this remarkable change in regioselectivity was elucidated by means of B3LYP, UHF and PM5 levels of calculation. The transition state (TS) analysis was used to rationalize this change in regioselectivity. The results indicate that a TS on the lowest-lying triplet potential energy surface may play an important role in controlling the regioselectivity. The role of the biradical intermediates and, in particular, the relative energies of the closure TS and the retro-cleavage TS leading to the original furanones were also studied. We observed that the behaviour of the biradicals that are appropriate for ring closure do not follow the so-called ‘rule of five’.

Regio- and Stereoselectivity in the Paterno-Buchi Reaction Between 2,3-Dihydrofuran and Furan with Benzaldehyde

The photochemical coupling reaction between 2,3-dihydrofuran and benzaldehyde was studied by using DFT/B3LYP/6-31G+(d,p) method. The regiochemistry of the attack of the benzaldehyde on the double bond is related to the different stability of the biradical intermediates. The endo stereoselectivity of the product depends on the superposition between HSOMO and LSOMO in the biradical intermediate. The photochemical reaction between furan and benzaldehyde was studied at the same level. The regioselectivity depends on the relative stability of the possible biradical intermediates. The exo stereoselectivity of the coupling product depends on the superposition between the HSOMO and LSOMO of the biradical intermediate.

Exploring Two-State Reaction Pathways in the Photodimerization of Cyclohexadiene

The ground- (S0) and lowest triplet-state (T1) pathways associated with dimerization of cyclohexadiene to give [2+2] and [4+2] cycloadducts have been theoretically studied at the UBLYP and UB3LYP levels of theory with the 6-31G* basis set. The DFT energies were validated by CCSD(T) single-point energy calculations. These cycloaddition reactions follow stepwise mechanisms with formation of bis-allylic biradical (BB) intermediates. In the S0 ground state, the interaction between two cyclohexadiene molecules with formation of BB intermediate IN(S0) has a large activation enthalpy of 32.0 kcal mol(-1). On the other hand, C-C bond-formation in the lowest triplet state (T1) leading to BB intermediate IN(T1) has a low activation enthalpy of 5.0 kcal mol(-1), but the subsequent ring closure involves a very large activation enthalpy of 43.4 kcal mol(-1). Triplet-to-singlet intersystem crossing from IN(T1) to IN(S0) favors cyclization to give the corresponding [2+2] and [4+2] cycloadducts.

Addition of Cyclopropyl Alkynes to a Brook Silene: Definitive Evidence for a Biradical Intermediate

The addition of three newly developed mechanistic probes, (trans-2-phenylcyclopropyl)ethyne, (trans,trans-2-methoxy-3-phenylcyclopropyl)ethyne, and (trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)ethyne, 1a-c, to a Brook silene, 2-tert-butyl-2-trimethylsiloxy-1,1-bis(trimethylsilyl)-1-silene, 10, was examined. When alkyne 1a was added to silene 10 products derived from a formal ene reaction were obtained. When alkynes 1b-c were added to silene 10, in addition to the typical silacyclobutenes, a variety of silacycloheptenes were obtained in which the cyclopropyl ring had clearly opened. Formal ene-addition products were also produced from the addition of 1b to 10. Based on the relative positions of the phenyl and methoxy substituents within the seven-membered ring of the silacycloheptenes and the known behavior of the alkyne probes under both radical and ionic conditions, it was concluded that a biradical intermediate was formed during the addition of alkynes 1b-c to silene 10. In the addition of alkynes 1a-b to silene 10, the ene products are most likely formed by a competitive pericyclic reaction. We also present a straightforward method for the unambiguous determination of the regiochemistry of silacyclobutenes derived from the cycloaddition of terminal alkynes to silenes.

Regio‐ and stereoselectivity in the Paternò‐Büchi reaction on furan derivatives

The photochemical coupling reaction between 2,3‐dihydrofuran and benzaldehyde was studied by using DFT/B3LYP/6 − 31G + (d, p) method. The regiocontrol of the attack of the benzaldehyde on the double bond is related to the different stabilities of the biradical intermediates. The endo stereoselectivity of the reaction depends on the superposition between HSOMO and LSOMO in the biradical intermediate. In the photochemical reaction between furan and benzaldehyde also the regiocontrol depends on the relative stability of the possible biradical intermediates. The exo stereoselectivity of the coupling reaction depends on the superposition between the HSOMO and LSOMO of the biradical intermediate. The reaction of chiral phenylglyoxylates with furan gave the corresponding adducts with de = 15–95%. The stereocontrol can be explained considering the energy gap between the biradical intermediates in the coupling reaction. When the reaction was performed in the presence of zeolite, the diastereoisomeric excess increased. The reaction of benzoin and 2‐phenylpropiophenone with furan gave the cycloadduct with high diastereocontrol. All the products were obtained with de > 98%. The Paterrnò‐Büchi reaction between 2‐furylmethanols with aromatic carbonyl compounds also showed high regio‐ and stereocontrol. On the contrary, when 5‐methyl derivatives were used, a lack of regiocontrol was observed. Furthermore, with aliphatic carbonyl compounds, no diastereoselectivity was observed. These results were explained assuming the attack of the excited carbonyl compound on the same side as the hydroxyl group, through the formation of a hydrogen bond or of a complex. This type of attack gave the biradical intermediate in preferential conformations. The relative energies of these conformers account for the observed diastereoselectivity.

Biradical Intermediate in the [2 + 2] Photocycloaddition of Dienes and Alkenes to [60]Fullerene

The photocycloaddition of vinylcyclopropanes to C60 yields stereospecifically a five-membered [60]fullerene adduct. These results suggest a biradical intermediate of the [2 + 2] photocycloaddition between dienes or arylalkenes and C60. An electron transfer between the triplet excited state of C60 and the unsaturated substrates precedes the formation of the intermediate.

The addition of alkynes to a tetrasilyldisilene — Evidence for a biradical intermediate

The addition of two newly developed mechanistic probes, (trans,trans-2-methoxy-3-phenylcyclopropyl)ethyne (1) and (trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)ethyne (2), to tetrakis(tert-butyldimethylsilyl)disilene (3) has been investigated. The addition of 1 to 3 gave 1-[2-(cis-2-methoxy-3-phenylcyclopropylidene)vinyl]-1,1,2,2-tetrakis(tert-butyldimethylsilyl)disilane (5) as the major product; whereas addition of alkyne 2 to the disilene gave three stereoisomers of 1,1,2,2-tetrakis(tert-butyldimethylsilyl)-6-methoxy-5-methyl-7-phenyl-1,2-disilacyclohepta-3,4-diene (7–9) and 1,1,2,2- tetrakis(tert-butyldimethylsilyl)-3-(trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)-1,2-disilacy-clobut-3-ene (10) as the major products. The formation of cycloheptaallenes 7–9 provides convincing evidence that the addition of alkynes to tetrasilyldisilenes involves the formation of a biradical intermediate. Key words: disilene, alkyne, cycloaddition, reaction mechanism, mechanistic probe.

Gas-phase thermolysis of benzotriazole derivatives. Part 3: Kinetic and mechanistic evidence for biradical intermediates in pyrolysis of aroylbenzotriazoles and related compounds

Gas-phase pyrolysis (static and FVP) of 1-aroylbenzotriazoles gave the corresponding substituted benzoxazole, benzimidazole, benzamide, N-phenylbenzamide, phenanthridin-6(5 H)-one derivatives and 1-cyanocyclopentadiene. The present kinetic and mechanistic findings also provide further evidence of the involvement of biradical or carbene reactive intermediates in the reaction pathway of gas-phase pyrolysis of benzotriazoles.