Diradical Reaction Research Articles

Activation Model and Origins of Selectivity for Chiral Phosphoric Acid Catalyzed Diradical Reactions.

To develop new radical synthesis strategies, a profound understanding of the electronic transfer mechanism is critical. An activation model called relayed proton-coupled electron transfer (relayed-PCET) was developed and investigated for chiral phosphoric acid-catalyzed diradical reactions by density functional theory (DFT). The driving force of electron transfer from the nucleophile to the electrophile is the proton transfer that occurs via the chiral phosphoric acid (CPA) catalyst to the electrophile. Moreover, the origins of the selectivity can be explained by distortion of the catalyst, favorable hydrogen bonding, and strong interactions of the substrates with substituents of the CPAs.

Heteroatom-Based Diradical(oid)s.

Heteroatom-centered diradical(oid)s have been in the focus of molecular main group chemistry for nearly 30 years. During this time, the diradical concept has evolved and the focus has shifted to the rational design of diradical(oid)s for specific applications. This review article begins with some important theoretical considerations of the diradical and tetraradical concept. Based on these theoretical considerations, the design of diradical(oid)s in terms of ligand choice, steric, symmetry, electronic situation, element choice, and reactivity is highlighted with examples. In particular, heteroatom-centered diradical reactions are discussed and compared with closed-shell reactions such as pericyclic additions. The comparison between closed-shell reactivity, which proceeds in a concerted manner, and open-shell reactivity, which proceeds in a stepwise fashion, along with considerations of diradical(oid) design, provides a rational understanding of this interesting and unusual class of compounds. The application of diradical(oid)s, for example in small molecule activation or as molecular switches, is also highlighted. The final part of this review begins with application-related details of the spectroscopy of diradical(oid)s, followed by an update of the heteroatom-centered diradical(oid)s and tetraradical(oid)s published in the last 10 years since 2013.

Understanding propyl cyanide and its isomers formation: ab initio study of the spectroscopy and reaction mechanisms.

Recent detection of propyl cyanide (C3H7CN) with both linear and branched structures has stimulated many experimental and theoretical studies. In this theoretical work, we present the spectroscopic properties of the far infrared spectra of these species and we investigate their different paths of formation in the gas phase. Our spectroscopic study concerns the far infrared spectra of iso, anti and gauche propyl cyanide isomers. The equilibrium structures and the potential energy surfaces are calculated using explicitly correlated cluster ab initio methods (CCSD(T)-F12) and a variational procedure designed for non-rigid species and large amplitude motions. Accurate rotational constants, centrifugal distortion constants, potential energy barriers and surfaces are provided. The rovibrational parameters in the ground vibrational states compare very well with experimental data. The low energy vibrational levels correspond to torsional modes. Far infrared energies are calculated up to 500 cm-1 using the variational approach and the vibrational second order theory (VPT2), and a good agreement with previous experimental values is found. We have also investigated the gas phase formation of the different C3H7CN isomers. After several trials of reacting gaseous species, we considered that a possible formation route of the C3H7CN isomers can be from the bimolecular reaction of HCN with propene. At the UMP2(full)/aug-cc-pVTZ level of theory, this reaction involves two steps for each isomer; the first one corresponds to the association of the two radicals while the second one corresponds to H transfer. From highly correlated ab initio calculations by means of CCSD(T)/aug-cc-pVTZ//UMP2(full)/aug-cc-pVTZ, the geometries, energetics and minimum energy paths of the reactions are obtained. Also, the first step's transition state disappears, as the diradical minimum is much less stabilized with UCCSD(T) than by UMP2(full). We employ the zero curvature tunneling and canonical variational (CVT/ZCT) semiclassical method to predict rate constants for propyl cyanide isomers formation in the gas phase. However, due to the presence of a significant barrier, this reaction leads to very small rate constants. Very recently, we probed reaction mechanisms involving radical addition and we found that these reactions are barrierless and highly exothermic leading to expected fast reactive processes for the formation of propyl cyanide products. The kinetics of such diradical reactions is under study.

Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin.

Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular styryl Diels-Alder reaction strategy uniquely suited to assemble the deoxypodophyllotoxin core. Density functional theory was used to analyze concerted, polar, and singlet-open-shell diradical reaction pathways, which identified a low-energy concerted [4 + 2] Diels-Alder pathway followed by a faster di-t-butylhydroxytoluene assisted [1,3]-formal hydrogen shift.

ChemInform Abstract: Diradical Reaction Mechanisms in [3 + 2]‐Cycloadditions of Hetaryl Thioketones with Alkyl‐ or Trimethylsilyl‐Substituted Diazomethanes.

AbstractDithiolanes are prepared by the title cycloaddition via diradical mechanism.

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes.

Reactions of dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were studied at variable temperature. The experiments showed that reactions with 2-diazopropane carried out at –75 °C occur mainly via the initially formed, relatively stable 1,3,4-thiadiazolines as products of the [3 + 2]-cycloaddition of the diazo dipole onto the C=S bond. The latter decompose only at higher temperature (ca. −40 °C) to generate thiocarbonyl S-isopropanide. In the absence of the starting thioketone, the corresponding thiiranes and/or ethene derivatives, formed from them via spontaneous desulfurization, are the main products. In contrast, reactions with diazoethane occurred predominantly via initially formed diradicals, which in cascade processes gave sterically crowded 4,4,5,5-tetrahetaryl-1,3-dithiolanes as major products. Finally, the reaction of dihetaryl thioketones with (trimethylsilyl)diazomethane occur smoothly at −75 °C leading to the corresponding 4,4,5,5-tetrahetaryl-1,3-dithiolanes as the exclusive [3 + 2]-cycloadducts formed via a cascade of postulated diradicals. The presence of S or Se atoms in the hetaryl rings is of importance for stabilizing diradical intermediates. Remarkably, in no single case, the ‘head-to-head dimerization’ of aryl/hetaryl and dihetaryl substituted thiocarbonyl ylides was observed.

Inquiry of the reaction paths in thermal retro-Diels–Alder reactions in the gas phase: Theoretical study on the concerted and stepwise elimination mechanisms of cyclohexenes

The mechanisms of the thermal decomposition of cyclohexene (CH), 4-methylcyclohexene (4MCH) and 4-vinyl cyclohexene (4VCH) in the gas-phase were studied by means of electronic structure calculations using perturbation MP2 and Density Functional Theory (DFT) methods. Molecular and diradical reaction pathways were calculated. In the case of the 4-susbstituted cyclohexenes two diradical processes were considered. DFT functionals, including a PT2 correction to the correlation energy, gave reasonable results for all reaction paths considered. Calculated parameters obtained with B2PLYP/6-31+G(d,p) are in good agreement with those reported in Tsang’s experimental study. Evaluated kinetic parameters indicate that CH, 4MCH, and 4VCH should follow the concerted molecular reaction pathway. However, it is possible that a fraction of the reactant molecules could overcome the energy barrier for the radical pathway, because of the high temperatures employed in the experimental conditions. The presence of methyl group in 4MCH slightly favors the breaking of C3C4 bond. The effect of vinyl group is more dramatic, consisted with a resonance effect stabilizing C3 throughout the bond breaking process. NBO charges suggest these processes are discretely polar, since there are slight variations in the electron density along the reaction coordinates. The analysis of the evolution percentages obtained from bond indexes suggests that these reactions are non-synchronous.

Extended Hartree–Fock theory of chemical reactions. IX. Diradical and perepoxide mechanisms for oxygenations of ethylene with molecular oxygen and iron‐oxo species are revisited

AbstractSymmetry and broken symmetry (BS) in molecular orbital description of transition structures and intermediates in oxygenation reactions have been revisited to elucidate states correlation diagrams and mechanisms for addition reactions of molecular oxygen and metal‐oxo MO (M = Mn(II) and Fe(II)) species to CC double bonds. Relative stabilities between diradical (DR) and perepoxide (PE) intermediates were thoroughly investigated by several BS hybrid DFT (HDFT) methods and BS CCSD(T) method with and without spin projection. It has been found that recovery of spin symmetry, namely eliminating spin contamination error from the BS solutions, is crucial for the elucidation of reasonable state correlation diagrams and energy differences of the key structures in the oxygenation reactions because the singlet‐triplet energy gap for molecular oxygen is large (22 kcal/mol). The BS HDFT followed by spin correction reproduced activation barriers for transition structures along both PE and DR reaction pathways by the use of the CASPT2 method. Basis set dependence on the relative stability between PE and DR intermediates were also examined thoroughly. Solvation effect for DR and PE intermediates was further examined with self‐consistent reaction field (SCRF) and SCIPCM methods. Both BS HDFT and CASPT2 have concluded that the DR mechanism is favorable for the addition reaction of singlet oxygen to ethylene, supporting our previous conclusions. The BS HDFT with spin correction was concluded to be useful enough for theoretical investigations of mechanisms of oxygenation reactions. Implications of the computational results were discussed in relation to the theoretical framework (four configuration model) for elucidation of possible mechanisms of epoxidation reactions with Fe(IV)O cores in metalloenzymes on the basis of isolobal analogies among O, OO, and Fe(IV)O. Correspondence between magnetic coupling mode and radical pathway in oxygenations with these species was clarified based on the BS MO interaction diagrams, leading to local singlet and triplet diradical mechanisms for epoxidations. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009

Theoretical Study of the Reaction Mechanisms Involved in the Thermal Intramolecular Reactions of 1,6-Fullerenynes

Substitution of a H atom by an alkyl group on the terminal carbon of the alkyne moiety of 1,6-fullerenynes has a strong impact on the products of the reaction undergone by this species after thermal treatment. While the reaction of 1,6-fullerenynes bearing an unsubstituted alkyne moiety results in the cycloaddition of the alkyne group to the fullerene double bond leading to cyclobutene-fused derivatives, the presence of an alkyl substituent leads to the formation of allenes. In the present work, we have performed an exhaustive theoretical analysis of all possible reaction mechanisms leading to cyclobutene-fused derivatives and allenes to offer an explanation of the reactivity differences observed. The results obtained show that formation of cyclobutene-fused derivatives occurs through a stepwise diradical reaction mechanism, while allene formation proceeds through a concerted way involving an uncommon intramolecular ene process. For the 1,6-fullerenynes bearing a substituted alkyne, the ene reaction path leading to allenes has an energy barrier somewhat lower than the stepwise diradical mechanism for the cyclobutene-fused derivative formation, thus explaining the outcome of the reaction.

Dry Synthesis of Triple Cumulative Double Bonds (CCCN) on Si(111)-7 × 7 Surfaces

The interactions of cyanoacetylene and diacetylene with a Si(111)-7 x 7 surface have been studied as model systems to mechanistically understand the chemical binding of unsaturated organic molecules to diradical-like silicon dangling bonds. Vibrational studies show that cyanoacetylene mainly binds to the surface through a diradical reaction involving both cyano and C[triple bond]C groups with an adjacent adatom-rest atom pair at 110 K, resulting in an intermediate containing triple cumulative double bonds (C=C=C=N). On the other hand, diacetylene was shown to the covalently attached to Si(111)-7 x 7 only through one of its C[triple bond]C groups, forming an enynic-like structure with a C=C-C[triple bond]C skeleton. These chemisorbed species containing triple cumulative double bonds (C=C=C=N) and C=C-C[triple bond]C may be employed as precursors (or templates) for further construction of bilayer organic films on the semiconductor surfaces.

Attachment of styrene and phenylacetylene on Si(111)-7 x 7: the influence of substitution groups on the reaction mechanism and formation of pi-conjugated skeletons.

The interactions of styrene and phenylacetylene and their isotope substitutions with a Si(111)-7 x 7 surface have been studied as model systems to mechanistically understand the chemical binding of conjugated pi-electron systems to di-radical-like silicon dangling bonds of the adjacent adatom-rest atom pair. Vibrational studies show that styrene mainly binds to the surface through a diradical reaction involving both the external C=C and its conjugated internal C=C of the phenyl ring with an adjacent adatom-rest atom pair, forming a 5-ethylidene-1,3-cyclohexadiene-like skeleton. On the other hand, phenylacetylene was shown to be covalently attached to Si(111)-7 x 7 through the external C[triple bond]C, forming a styrene-like conjugation system. These experimental results are consistent with density functional theory calculations. The different binding mechanisms for styrene and phenylacetylene clearly demonstrate that reaction channels for multifunctional organic molecules are strongly dependent on the chemical and physical properties of the functional groups. The resulting pi-electron conjugation structures may possibly be employed as intermediates for further organic syntheses and fabrication of multilayer organic films on semiconductor surfaces.

High Level ab Initio Study of Thermal 1,3-Sigmatropic Shift in CH2CHCH2X with X = BH2, NH2, and CH3

The thermal 1,3-sigmatropic migrations in X-CH2−CHCH2 with X = BH2, NH2, and CH3 have been investigated at the RHF, MP2, B3LYP, G3, and CBS-APNO levels using basis sets with added diffuse and polarization functions. In all three cases, the suprafacial allowed path proceeds through a TS in which the CC π electron is delocalized into the 2p AO in the migrating X. For X = BH2 with a vacant 2p orbital, the activation enthalpy is less than 1.0 kcal mol-1 (CBS-APNO) so that the 1,3-shift is almost barrierless. For X = NH2 there are two suprafacial pathways, one of which (higher energy path a) proceeds by participation of the lone pair on N. The lower energy pathway has a barrier height (ΔH⧧ = 68.9 kcal mol-1) of only 1.0 kcal mol-1 below the bond dissociation energy of the C1−N bond, so that a diradical pathway can compete with the concerted sigmatropic shift. For X = CH3, the activation barrier (ΔH⧧ = 76.1 kcal mol-1) is higher (by ca. 1 kcal mol-1 at the CBS-APNO level) than the bond dissociation energy of the C1−X(CH3) bond, so that the diradical reaction path is favored. The antrafacial 1,3-shifts are forbidden in all cases as evidenced by the second-order saddle-points (with two imaginary frequencies) and much higher barrier heights than those for the corresponding suprafacial shifts.

Abstraction of deuterium from dideuteroglycine by aryl radical: A model for 1, 4-benzene diradical reactions with proteins

Aryl radicals are generated by oxidation of aryl hydrazine with PbO 2 or via photolysis of aryl iodide. Abstraction of deuterium from dideuteroglycine derivatives is demonstrated as a model for the possible reaction of 1, 4-aryl diradicals with amino acid residues in proteins.

On the mechanism of the benzophenone‐sensitized photolysis of 2,3‐diazabicyclo[2.2.1]hept‐2‐ene in the laser jet: Evidence for intermolecular triplet diradical reactions

AbstractThe benzophenone‐sensitized laser jet photolysis of 2,3‐diazabicyclo[2.2.1]hept‐2‐ene (1) affords, besides the previously reported cyclopentene and housane (2), also cyclopentane, cyclopentadiene, and the dimers bicyclopent‐2‐en‐1‐yl (7), 3‐cyclopentylcyclopent‐1‐ene (8), and 1,1'‐bicyclopentyl (9). As a model reaction, the pyrolysis of dimer 8 at 600°C/20 Torr leads to the other dimers 7 and 9 together with cyclopentadiene, cyclopentene, and traces of cyclopentane. Control experiments showed that H abstraction by the cyclopentane‐1,3‐diyldiracidal (3) from cyclohexene (as model substrate for cyclopentene) and addition to housane (2) with formation of diradical 6 are unlikely pathways. Instead, the product data available can be best explained in terms of an intermolecular disproportionation of two diradicals 3 to give the cyclopent‐2‐en‐1‐yl (4) and cyclopentyl (5) radical pair, which is subsequently converted to the observed products by in‐cage and out‐of‐cage coupling and H transfer reactions. Such intermolecular diradical chemistry becomes feasible due to the high steady‐state concentrations (ca, micromolar) generated in the laser jet. Two‐photon processes take place, but are of subordinate importance.

Spiroheterocycles from the reaction of nitrile oxides with 3-methylenephthalimidines

We found that reaction of aromatic nitrile oxides with 3-methylenephthalimidines 8 produced spiroheterocycles 9. When N-benzyl-3-methylenephthalimidine (8c) was employed, oximes 10 and 11 were formed in addition to the spiroheterocycles. Solvent effects on the reaction rates and on product ratios indicate that the product mixtures result from competition between a 1,3-cycloaddition reaction of nitrile oxide with 8 to produce a spiroheterocycle and a diradical reaction of nitrile oxide with 8 to produce the oximes

The RHF– and UHF–AM1 potential-energy surfaces for the diels–alder reaction of substituted butadienes with substituted ethenes. Part 58.—Determination of reactivity by MO theory

The potential-energy surfaces for the Diels–Alder reactions between substituted butadienes and ethenes have been investigated by intensive RHF- and UHF-grid searches using the AM1 method. The RHF/AM1 potential surface show a concerted, synchronous path, but the UHF/AM1 potential surface has four transition states, two intermediates and two maxima with two stepwise, diradical reaction paths. The diagonal, concerted path in the UHF/AM1 potential surface vanishes owing to the coalescence of two maxima induced by the two stable intermediates on the two-dimensional contour diagram. Substituent effects on the activation barriers are of electronic and steric origin, and only the UHF/AM1 results agreed with experiments.

Energy gradient in a multi-configurational SCF formalism and its application to geometry optimization of trimethylene diradicals

Previous methods of analytic evaluation of the potential energy gradient with respect to nuclear coordinates have been limited to single determinant Hartree-Fock wavefunctions. An expression and a practical method are presented for analytic gradient evaluation for MCSCF wavefunctions of certain widely applicable types. A geometry optimized of trimethylene diradical reaction intermediates has been actually accomplished by the use of the energy gradient for an ab initio MCSCF wavefunction.