DFT Calculations Rationalize Unconventional Regioselectivity in PdII-Catalyzed Defluorinative Alkylation of gem-Difluorocyclopropanes with Hydrazones.

Density functional theory (DFT) calculations have been conducted to gain insight into the unique formation of the branched alkylation product in the PdII-catalyzed defluorinative alkylation of gem-difluorocyclopropanes with hydrazones. The reaction is established to occur in sequence through oxidative addition, ß-F elimination, η1-η3 isomerization, transmetalation, η3-η1 isomerization, 3,3'-reductive elimination, deprotonation/N2 extrusion, and proton abstraction. The rate-determining step of the reaction is identified as the ß-F elimination, featuring an energy barrier of 28.6 kcal/mol. The 3,3'-reductive elimination transition states are the regioselectivity-determining transition states. The favorable noncovalent π-π interaction between the naphthyl group of gem-difluorocyclopropane and the phenyl group of hydrazone is found to be mainly responsible for the observed regioselectivity.

Theoretical Insight into the Palladium-Catalyzed Prenylation and Geranylation of Oxindoles with Isoprene.

This work presents a comprehensive mechanistic study of the ligand-controlled palladium-catalyzed prenylation (with C5 added) and geranylation (with C10 added) reactions of oxindole with isoprene. The calculated results indicate that the prenylation with the bis-phosphine ligand and geranylation with the monophosphine ligand fundamentally share a common mechanism. This mechanism involves the formation of two crucial species: a η3-allyl-Pd(II) cation and an oxindole carbon anion. Furthermore, the reactions necessitate the assistance of a second oxindole molecule, which serves as a Brønsted acid, providing a proton to generate the oxindole nitrogen anion. The oxindole nitrogen anion then acts as a Brønsted base, abstracting a C-H proton from another oxindole molecule to form an oxindole carbon anion. These mechanistic details differ significantly from those proposed in the experimental work. The present calculations do not support the presence of the Pd-H species and the η3, η3-diallyl-Pd(II) intermediate, which were previously suggested in experiments. The theoretical results rationalize the experimental finding that the bis-phosphine ligand favors the prenylation of oxindole, while the monophosphine ligand enables the geranylation of oxindole.

Density Functional Theory Study of Gold-Catalyzed 1,2-Diarylation of Alkenes: π-Activation versus Migratory Insertion Mechanisms.

Density functional theory calculations are carried out to better understand the first gold-catalyzed 1,2-diarylation reactions of alkenes reported in the recent literature. The calculations on two representative reactions, aryl alkene/aryl iodide coupling pair (the aryl-I bond is located outside the aryl alkene) versus iodoaryl alkene/indole coupling pair (the aryl-I bond is located in the aryl alkene), confirm that the reaction involves a π-activation mechanism rather than the general migratory insertion mechanism in previously known metal catalysis by Pd, Ni, and Cu complexes. Theoretical results rationalize the regioselectivity of the reactions controlled by the aryl-I bond position (intermolecular or intramolecular) and also the ligand and substituent effects on the reactivity.

DFT Mechanistic Study of IrIII/NiII-Metallaphotoredox-Catalyzed Difluoromethylation of Aryl Bromides.

The work by MacMillan et al. ( Angew. Chem., Int. Ed. 2018, 57, 12543-12548) developed an IrIII/NiII-metallaphotoredox-catalyzed difluoromethylation strategy of aryl bromides using CHF2Br as the CHF2 reagent in the presence of tris(trimethylsilyl)silane. Here, we present a density functional theory (DFT)-based computational study to understand special dual catalysis promoting the C(sp2)-C(sp3) coupling. The calculated results show that the energetically more favorable pathway involves the reductive quenching of a photocatalyst (IrIII/*IrIII/IrII/IrIII) and a Ni0-initiated catalytic cycle (Ni0/NiI/NiIII/NiI/Ni0 or Ni0/NiII/NiIII/NiI/Ni0). The calculations reveal not only the mechanistic details delivering the difluoromethylarene product but also the molecular-level picture of the generation of Ni0 species from the NiII precatalyst. Moreover, the calculations also rationalize the observed stoichiometric effect of CHF2Br in the reactions of aryl bromides with different substituted groups.

Mechanistic Insight into Palladium-Catalyzed γ-C(sp3)-H Arylation of Alkylamines with 2-Iodobenzoic Acid: Role of the o-Carboxylate Group.

Density functional theory calculations were performed to understand the distinctly different reactivities of o-carboxylate-substituted aryl halides and pristine aryl halides toward the PdII-catalyzed γ-C(sp3)-H arylation of secondary alkylamines. It is found that, when 2-iodobenzoic acid (a representative of o-carboxylate-substituted aryl halides) is used as an aryl transfer agent, the arylation reaction is energetically favorable, while when the pristine aryl halide iodobenzene is used as the aryl transfer reagent, the reaction is kinetically difficult. Our calculations showed an operative PdII/PdIV/PdII redox cycle, which differs in the mechanistic details from the cycle proposed by the experimental authors. The improved mechanism emphasizes that (i) the intrinsic role of the o-carboxylate group is facilitating the C(sp3)-C(sp2) bond reductive elimination from PdIV rather than facilitating the oxidative addition of the aryl iodide on PdII, (ii) the decarboxylation occurs at the PdII species instead of the PdIV species, and (iii) the 1,2-arylpalladium migration proceeds via a stepwise mechanism where the reductive elimination occurs before decarboxylation, not via a concerted mechanism that merges the three processes decarboxylation, 1,2-arylpalladium migration, and C(sp3)-C(sp2) reductive elimination into one. The experimentally observed exclusive site selectivity of the reaction was also rationalized well.

Theoretical Insight into the Au(I)-Catalyzed Intermolecular Condensation of Homopropargyl Alcohols with Terminal Alkynes: Reactant Stoichiometric Ratio-Controlled Chemodivergence.

The mechanisms and chemoselectivities on the Au(I)-catalyzed intermolecular condensation between homopropargyl alcohols and terminal alkynes were investigated by performing DFT calculations. The reaction was indicated to involve three stages: transformation of the homopropargyl alcohol (R1) via intramolecular cyclization to the cyclic vinyl ether (R1'), formation of the C-2-arylalkynyl cyclic ether (P1) via hydroalkynylation of R1' with phenylacetylene (R2), and conversion from P1 to 2,3-dihydro-oxepine (P2). The results revealed the origin of the reaction divergence and rationalized the experimental observations that a 1:3 reactant stoichiometric ratio affords P1 as the major product, whereas the 1:1.1 ratio results in P2 in high yield. The reactant stoichiometric ratio-controlled divergent reactivity is attributed to different catalytic activities of the gold catalyst toward different reaction stages. In the 1:3 situation, the excess R2 induces the Au catalyst toward its dimerization and/or hydration, inhibiting the conversion of P1 to P2 and resulting in product P1. Without excess R2, the Au catalysis follows a general cascade reaction, leading to product P2. Theoretical results described a general strategy controlling the reaction divergence by a different reactant stoichiometric ratio. This strategy may be enlightening for chemists who are exploring various synthesis methods with high chemo-, regio-, and enantioselectivities.

Theoretical Insight into the Mechanism and Origin of Divergent Reactivity in the Synthesis of Benzo-Heterocycles from o-Alkynylbenzamides Catalyzed by Gold and Platinum Complexes.

This work presents a DFT study on the mechanism and origin of catalyst-controlled divergent reactivity in the synthesis of benzo-heterocycles from o-alkynylbenzamides by Au(I)/Pt(IV) catalysis. The results indicate that the transformations proceed via a nucleophilic cyclization process. In the Au(I) catalysis, the preferred O-attack mode mainly originates from the symmetry match in the dominant bond-forming interaction between the lone-pair orbital of carbonyl-O and the in-plane alkyne π* orbital, and the electronic property of the ligand controls the O-5-exo-dig/O-6-endo-dig selectivity. The preference for the N-attack mode in Pt(IV) catalysis is attributed to the stronger coordinate capability of carbonyl-O than amino-N in the substrate to PtCl4, and the regioselective N-6-endo-dig or N-5-exo-dig cyclization depends on the stronger electrostatic interaction between the amino-N and alkynyl-Cß atoms. The theoretical results provide a fundamental understanding of why and how gold and platinum complexes catalyze the cyclization of o-alkynylbenzamides with different chemo- and regioselectivities.

DFT Study on Photosensitizer-Free Visible-Light-Mediated Au-Catalyzed cis-Difunctionalization of Alkynes: Mechanism and Selectivities as Compared to Rh Catalysis.

Density functional theory (DFT) calculations were performed to investigate the photosensitizer-free visible-light-mediated gold-catalyzed cis-difunctionalization of alkynes with aryl diazonium salts. The detailed reaction mechanism is established, and the observed regio- and chemoselectivities are rationalized. The results are compared to those of the rhodium-catalyzed cis-difunctionalization of alkynes. It is indicated that the excitation of the aryl diazonium salt initiates the photocatalytic cycle, and the following single-electron transfer between the Au(I) catalyst and the excited aryl diazonium salt affords the key aryl radical. Both gold- and rhodium-catalyzed reactions involve two major steps: alkyne insertion into the M-N or M-C bond (M = Au, Rh), and C-C or C-N reductive elimination from the M(III) center. The cis-difunctionalized product can be obtained by the trimethylsilyl (TMS)-substituted alkyne through the gold catalysis or by the Ph-substituted alkyne through the rhodium catalysis. The catalyst-dependent reactivity switch of TMS- and Ph-substituted alkynes is attributed to the catalyst-induced shift of the rate-determining step.

Mechanistic Study on the Decarboxylative sp3 C-N Cross-Coupling between Alkyl Carboxylic Acids and Nitrogen Nucleophiles via Dual Copper and Photoredox Catalysis.

This work presents a density functional theory (DFT)-based theoretical study on the cross-coupling reaction of alkyl carboxylic acids and nitrogen nucleophiles via dual copper and photoredox catalysis developed by MacMillan et al. [Nature, 2018, 559, 83-87]. The calculations showed the mechanistic details of three subprocesses proposed in the experimental study, including production of alkyl radicals, iridium(III) photoredox cycle, and copper(I) thermalredox cycle. It is found that alkyl radicals can be easily produced from primary, secondary, or tertiary carboxylic acids through iodonium activation. The energetically most favorable cross-coupling pathway involves coordination, deprotonation, single electron transfer (SET), radical addition, and reductive elimination. For the chlorinated indazole nucleophile (R1), the preferred C-N coupling product from the 1H-tautomer is attributed to its higher stability relative to the 2H-tautomer and the high barrier involved in the tautomerism from the 1H-tautomer to the 2H-tautomer. Meanwhile, in the case of heterocycle (R2), the C-N cross-coupling preferentially occurs at the indazole nitrogen rather than at the primary amide nitrogen, which is confirmed to be due to the stronger acidity of the indazole N-H unit, in comparison with the primary amide N-H unit in the indazole side chain. The theoretical results provide help for understanding the molecular mechanism and regioselectivity of the title reaction.

The Dual Role of Gold(I) Complexes in Photosensitizer-Free Visible-Light-Mediated Gold-Catalyzed 1,2-Difunctionalization of Alkynes: A DFT Study.

Recently, a photosensitizer-free visible-light-mediated gold-catalyzed 1,2-difunctionalization of alkynes has been developed. However, mechanistic aspects of this unconventional photocatalytic reaction remain largely obscure. With the aid of density functional theory (DFT) and time-dependent (TD)DFT calculations, we mimicked the photosensitizer-free visible-light-mediated gold-catalyzed 1,2-difunctionalization of 1-phenyl-1-hexyne and focused on two fundamental questions: how does photoredox catalysis occur without assistance of an exogenous photosensitizer under visible light irradiation, and what is the detailed mechanism of the gold-catalyzed 1,2-difunctionalization of alkynes? The results reveal the dual role of the gold(I) complex in light-harvesting and catalysis, where a charge-transfer (CT) complex formed by the association of gold(I) catalyst with PhN2 BF4 acts as a photosensitizer, which can undergo an electronic transition between the gold(I) moiety and PhN2 BF4 of the CT complex into an excited electronic state and afford a charge-transfer exciplex. The oxidative quenching of the exciplex generates the gold(II) species and diazobenzene radical. The subsequent catalytic cycle proceeds via two parallel pathways, involving the radical addition to gold(II) and gold(I) centers, respectively, and in these two pathways the reductive elimination of gold(III) species is identified as the rate-determining step of the whole reaction. The present study could provide a new understanding for exogenous-photosensitizer-free visible-light-mediated gold-catalyzed processes.

Theoretical Insight into the Mechansim and Origin of Ligand-Controlled Regioselectivity in Homogenous Gold-Catalyzed Intramolecular Hydroarylation of Alkynes.

This work aims at understanding the mechanism and regioselectivity in ligand-controlled gold-catalyzed divergent intramolecular hydroarylation of alkynes reported by Jiang et al. ( J. Am. Chem. Soc. 2016 , 138 , 5218 - 5221 ). Focusing on a representative alkyne, N-propargyl-N-tosylaniline, we conducted a detailed computational study on the ortho- and para-position hydroarylation of the alkyne catalyzed by gold(I) catalysts with different ligands. Both the ortho- and para-position hydroarylation reactions are found to follow a similar three-stage mechanism: electrophilic cyclization, proton loss, and protiodeauration. The initial electrophilic cyclization was identified as the rate- and regiochemistry-determining step. With the flexible electron-deficient phosphite ligand, the ortho-position cyclization is identified as the energetically more favorable pathway, while with the rigid electron-abundant phosphine (Xphos) ligand, the dominant pathway turns to the para-position cyclization. The theoretical results are in good agreement with the experimental observations. The π-π interaction between alkynyl phenyl and the directing acylamino group are found to be mainly responsible for the observed ortho-selectivity, while a combination of favorable noncovalent CH···π interaction and steric repulsion between Xphos ligand and alkynyl group contributes to the observed exclusive para-selectivity. The present calculations provide deeper insight into the mechanism and origin of regioselectivity of the title reaction.

Theoretical insight into the mechanism, regioselectivity, and substituent group effect of Rh-catalyzed synthesis of 1,2-benzothiazines from NH-sulfoximines and diazo compounds.

This work presents a computational study of RhIII-catalyzed synthesis of 1,2-benzothiazines from NH-sulfoximines and diazo compounds reported by Bolm et al. (Angew. Chem., Int. Ed., 2015, 54, 12349). The reaction involves five sequent processes: elimination of dinitrogen, C-H activation, carbene insertion, protonation, and dehydration, and the C-H activation is identified as the rate-determining step with a barrier of 33.1 kcal mol-1. Phenyl sulfoximine is found to be the most favorable substrate with the lowest barrier in comparison with methoxybenzene sulfoximine and nitrobenzene sulfoximine. The noncovalent interaction is indicated to be mainly responsible for the experimentally observed regioselectivity. The theoretical results are expected to provide valuable guidance and assistance for the synthesis of 1,2-benzothiazines.

Modeling interactions between a ß-O-4 type lignin model compound and 1-allyl-3-methylimidazolium chloride ionic liquid.

Aiming at understanding the molecular mechanism of the lignin dissolution in imidazolium-based ionic liquids (ILs), this work presents a combined quantum chemistry (QC) calculation and molecular dynamics (MD) simulation study on the interaction of the lignin model compound, veratrylglycerol-ß-guaiacyl ether (VG) with 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The monomer of VG is shown to feature a strong intramolecular hydrogen bond, and its dimer is indicated to present important π-π stacking and intermolecular hydrogen bonding interactions. The interactions of both the cation and anion of [Amim]Cl with VG are shown to be stronger than that between the two monomers, indicating that [Amim]Cl is capable of dissolving lignin. While Cl- anion forms a hydrogen-bonded complex with VG, the imidazolium cation interacts with VG via both the π-π stacking and intermolecular hydrogen bonding. The calculated interaction energies between VG and the IL or its components (the cation, anion, and ion pair) indicate the anion plays a more important role than the cation for the dissolution of lignin in the IL. Theoretical results provide help for understanding the molecular mechanism of lignin dissolution in imidazolium-based IL. The theoretical calculations on the interaction between the lignin model compound and [Amim]Cl ionic liquid indicate that the anion of [Amim]Cl plays a more important role for lignin dissolution although the cation also makes a substantial contribution.

Theoretical Elucidation of the Mechanism and Kinetic Experimental Phenomena on the Esterification of α-Tocopherol with Succinic Anhydride: Catalysis of a Histidine Derivative vs an Imidazolium-Based Ionic Liquid.

DFT calculations have been conducted to gain insight into the mechanism and kinetics of the esterification of α-tocopherol with succinic anhydride catalyzed by a histidine derivative or an imidazolium-based ionic liquid (IL). The two catalytic reactions involve an intrinsically consistent molecular mechanism: a rate-determining, concerted nucleophilic substitution followed by a facile proton-transfer process. The histidine derivative or the IL anion is shown to play a decisive role, acting as a Brönsted base by abstracting the hydroxyl proton of α-tocopherol to favor the nucleophilic substitution of the hydroxyl oxygen of α-tocopherol on succinic anhydride. The calculated free energy barriers of two reactions (15.8 kcal/mol for the histamine-catalyzed reaction and 22.9 kcal/mol for the IL-catalyzed reaction) together with their respective characteristic features, the catalytic reaction with a catalytic amount of histamine vs the catalytic reaction with an excessed amount of the IL, rationalize well the experimentally observed kinetics that the former has faster initial rate but longer reaction time while the latter is initiated slowly but completed in a much shorter time.

The mechanism for the formation of OH radicals in condensed-phase water under ultraviolet irradiation.

Irradiation on liquid water and ice by ultraviolet light in the range of 150-200 nm can create volatile OH radicals which react with other organic and inorganic molecules actively. However, the mechanism for OH radical formation in the condensed-phase water in this energy range is still unclear. To uncover this mechanism we studied the excited-state behaviors of ice using first-principles calculations based on many-body Green's function theory. First, we showed that the long-wavelength optical absorption at the Urbach tail (190-300 nm) can be attributed to inherent hydroxide ions or transient structures formed in the autoionization process. Second, we revealed that creation of the OH radicals can be attributed to two mechanisms. Irradiation by the light at the Urbach tail excites an electron out of the hydroxide ion, leaving a neutral OH radical behind. By the light around 150 nm, OH radicals can be produced barrierlessly via direct water photolysis through concerted proton and electron transfer. Our results provide valuable insights into the excited-state dynamics of condensed-phase water, helping us understand in depth the photocatalytic reactions, radiation biology and chemistry.

New Insight into the Formation Mechanism of Imidazolium-Based Ionic Liquids from N-Alkyl Imidazoles and Halogenated Hydrocarbons: A Polar Microenvironment Induced and Autopromoted Process.

To illustrate the formation mechanism of imidazolium-based ionic liquids (ILs) from N-alkyl imidazoles and halogenated hydrocarbons, density functional theory calculations have been carried out on a representative system, the reaction of N-methyl imidazole with chloroethane to form 1-ethyl-3-methyl imidazolium chloride ([Emim]Cl) IL. The reaction is shown to proceed via an SN2 transition state with a free energy barrier of 34.4 kcal/mol in the gas phase and 27.6 kcal/mol in toluene solvent. The reaction can be remarkably promoted by the presence of ionic products and water molecules. The calculated barriers in toluene are 22.0, 21.7, and 19.9 kcal/mol in the presence of 1-3 ionic pairs of [Emim]Cl and 23.5, 21.3, and 19.4 kcal/mol in the presence of 1-3 water molecules, respectively. These ionic pairs and water molecules do not participate directly in the reaction but provide a polar environment that favors stabilizing the transition state with large charge separation. Hence, we propose that the synthesis of imidazolium-based ILs from N-alkyl imidazoles and halogenated hydrocarbons is an autopromoted process and a polar microenvironment induced reaction, and the existence of water molecules (a highly polar solvent) in the reaction may be mainly responsible for the initiation of reaction.

Spin-state energies of heme-related models from spin-flip TDDFT calculations.

Spin-state energies of heme-related models are of vital importance in biochemistry. To compute the energies of different spin states, the traditional ΔSCF method based on the density functional theory (DFT) is usually employed. In this work, the spin-flip TDDFT (SF-TDDFT) approach is investigated to compute the spin-state energies, with six different exchange-correlation (XC) functionals. With the present protocol, the spin contamination is fully avoided by choosing appropriate reference states. Additionally, multiple excited states can be obtained with SF-TDDFT. Compared with the CCSD(T) results, it is shown that the SF-TDDFT calculations with the BHandHLYP functional provide better accuracy than ΔSCF for D-Q (doublet-quartet) and Q-S (quartet-sextet) gaps and agree well with the experimental results. A possible solution for the precise calculation of spin-state energies is proposed to improve the performance of SF-TDDFT, on account of that the excitation energies show highly linear dependence on the amount of Hartree-Fock (HF) exchange in the XC functionals.

Tetraalkylammonium interactions with dodecyl sulfate micelles: a molecular dynamics study.

All-atom molecular dynamics (MD) simulations were performed to study the effects of different tetraalkylammonium (TAA(+)) counterions, including tetramethylammonium (TMA(+)), tetraethylammonium (TEA(+)), tetrapropylammonium (TPA(+)) and tetrabutylammonium (TBA(+)), on dodecyl sulfate (DS(-)) micelles. Structural properties, such as the radius of gyration (Rg), micelle radius (Rs), micelle size, solvent accessible surface area (SASA), carbon and sulfur distribution, hydration numbers, and distribution of polar heads on the micelle surface, were investigated. The simulation results show that the longer the carbon chains of the TAA(+) counterion, the greater the radius of the micelle formed. TMA(+) leads to the most compact structure of the DS(-) micelle among the five studied systems and DS(-) and TAA(+) formed mixed-micelles. There are mainly four interaction patterns between TAA(+) and DS(-) ions, and the pattern in which two alkyl chains of the TAA(+) ion penetrate into the DS(-) micelle is the most favorable one. Based on the preceding analysis, a model based on this MD method is proposed.

Origins of entropy change for the amphiphilic molecule in micellization: a molecular dynamics study.

The micellization of amphiphilic molecules is an important phenomenon in the natural world. However, the origin of entropy change during micellization is still unclear. Molecular dynamics simulation was applied to study configurational entropy change of amphiphilic molecules in micellization. The entropy change of polar heads, hydrophobic chains, vibration, translation and rotation are discussed. Analyses provide a clear physical picture of the entropy increase in micellization, and thus foundations for further study.

Optical properties of acene molecules and pentacene crystal from the many-body Green's function method.

Acene is a type of important organic semiconductor which has promising applications in various optoelectronic devices. The fission of a singlet to triplet in it has been expected to elevate the quantum efficiency of organic solar cells. However, the quantum efficiency is still very low and the fission process is still under debate. Controversies also exist on the energies of the singlet and triplet states in acene. Using the many-body Green's function theory, which includes the GW method and Bethe-Salpeter equation (BSE), we compared the electronic excited states of several kinds of acene molecules (naphthalene to pentacene) at geometries optimized by different approaches. The energies of both the singlet and triplet depend strongly on the geometries of the molecules and their stacking. The non-negligible contribution from the resonant and anti-resonant transition coupling can cause large errors of the Tamm-Dancoff approximation, and the full BSE is required to get accurate results which are consistent with experiments. We found that accurate ionization energies and exciton energies can only be obtained when the geometries optimized by the Hartree-Fock approach are used. Singlet fission may be realized in isolated molecules, clusters, and surfaces, but it is hard in perfect pentacene crystals energetically. We provide a methodology for future research on acene-based solar cells and other optoelectronic devices.