Palladium-Catalyzed Sequential Cross-Coupling/Annulation of ortho-Vinyl Bromobenzene with Aryl Bromide: Bimetallic Pathway versus Pd(II)-Pd(IV) Pathway: A DFT Investigation.

The palladium-catalyzed sequential cross-coupling/annulation of ortho-vinyl bromobenzenes with aryl bromides generating phenanthrenes was characterized by density functional theory (DFT). The Pd(II)-Pd(IV) pathway (Path V) is shown to be less probable than the bimetallic pathway (Path I), the latter proceeding via the following six steps: oxidative addition, vinyl-C(sp2)-H activation, Pd(II)-Pd(II) transmetalation, C-C coupling, aryl-C(sp2)-H activation, and reductive elimination. The aryl-C(sp2)-H activation process acts as the rate-determining step (RDS) of the entire chemical transformation, with an activation free energy barrier of ca. 27.4-28.8 kcal·mol-1, in good agreement with the corresponding experimental data (phenanthrenes' yields of ca. 65-90% at 130 °C after 5 h of reaction). The K2CO3 additive effectively reduces the activation free energy barrier of the RDS through direct participation in the reaction while preferentially modulating the charge distributions and increasing the stability of corresponding intermediates and complexes along the reaction path. Furthermore, bonding and electronic structure analyses of the key structures indicate that the chemo- and regioselectivities of the reaction are strongly influenced by both electronic effects and steric hindrance.

Pd-NHC catalysed regioselective activation of B(3,6)-H of o-carborane - a synergy between experiment and theory.

Regioselective B-H activation of o-carboranes is an effective way for constructing o-carborane derivatives, which have broad applications in medicine, catalysis and the wider chemical industry. However, the mechanistic basis for the observed selectivities remains unresolved. Herein, a series of density functional theory (DFT) calculations were employed to characterise the palladium N-heterocyclic carbene (Pd-NHC) catalysed regioselective B(3,6)-diarylation of o-carboranes. Computational results at the IDSCRF(ether)-LC-ωPBE/BS1 and IDSCRF(ether)-LC-ωPBE/BS2 levels showed that the reaction undergoes a Pd(0) → Pd(II) → Pd(0) oxidation/reduction cycle, with the regioselective B(3)-H activation being the rate-determining step (RDS) for the full reaction profile. The computed RDS free energy barrier of 24.3 kcal mol-1 agrees well with the 82% yield of B(3,6)-diphenyl-o-carborane in ether solution at 298 K after 24 hours of reaction. The Ag2CO3 additive was shown to play a crucial role in lowering the RDS free energy barrier and facilitating the reaction. Natural charge population (NPA) and molecular surface electrostatic potential (ESP) analyses successfully predicted the experimentally observed regioselectivities, with electronic effects being revealed to be the dominant contributors to product selectivity. Steric hindrance was also shown to impact the reaction rate, as revealed by experimental and computational characterisation studies of substituents and ligand effects. Furthermore, computational predictions aligned with the experimental findings that NHC ligands outperform the phosphine ones for this particular reaction. Overall, the observed trends reported in this work are expected to assist in the rational optimisation of the efficiency and regioselectivity of this and related reactions.

Electronic and Steric Control of Rates and Selectivities in Rhodium-Catalyzed [2+2+2] Cycloadditions for Constructing Fused Tricyclic Hydronaphthofurans: A Density Functional Theory Study.

Fused tricyclic hydronaphthofurans with multiple chiral centers are very important skeletons for constructing natural products; however, their synthesis is challenging, and a detailed understanding of the final formation mechanism remains elusive. In this work, density functional theory computations were employed to characterize rhodium-catalyzed [2+2+2] cycloaddition of enyne with terminal alkynes. The putative mechanism involves an initial ligand exchange, followed by oxidative cyclization, olefin insertion, and reductive elimination processes. Oxidative cyclization is shown to be the rate- and selectivity-determining step of the full chemical transformation, where the R substituent on terminal alkynes has a significant influence on the reaction selectivities. When R is an electron-donating group (OMe and Me), the ortho-substituted tricyclic hydronaphthofurans (P1) are predicted to be dominant; on the contrary, meta-substituted compounds P2 emerge as the main products when R is an electron-withdrawing group (NO2, CF3, and CN). Computational predictions for selectivity are in good agreement with experimental product ratios. Free energy barriers of the rate-determining step for P1 and P2 are ∼22.3-23.6 kcal mol-1, which align well with their experimental yields of ∼79-92% at 313 K after 0.5 h. The results also accurately reproduce experimentally observed regio-, chemo-, and enantioselectivities, with steric hindrance as well as electronic properties of the substrate and ligand markedly influencing the reaction rates and selectivities. The influence of computational methods is also explored and discussed in detail.

Electronic Effect-Guided, Palladium-Catalyzed Regioselective B-H Activation and Multistep Diarylation of o-Carboranes with Aryl Iodides.

Density functional theory calculations at IDSCRF-B3LYP/DZVP computational level were conducted on palladium-catalyzed regioselective B-H activation and diarylation of o-carboranes with aryl iodides in solution. Computational results indicate that this reaction follows a multistep mechanism and needs to get over several transition states before the final B(4,5)-diarylated o-carborane derivatives are formed. B-H activation, oxidation addition, and successive reduction of the Pd(II) catalyst involving a Pd(II)-Pd(IV)-Pd(II) catalytic cycle has been confirmed, in which AgOAc plays a crucial role. Electron-donating group on the cage carbon of o-carboranes is verified to be beneficial for its B-H activation and diarylation, while steric hindrance between the aryl and o-carboranyl groups retards it. Natural population analysis and Gibbs free energetic results predict consistent regioselectivities with experiments and manifest the pivotal role of electronic effect in controlling regioselective B-H activation of o-carboranes. These results are expected to shed some light on further improvement of experimental conditions and better controlling of regioselectivities.

The pivotal role of electronics in preferred alkene over alkyne Ni-carboryne insertions and absolute regioselectivities.

The in situ formation mechanisms of active Ni-carboryne species (COM1) and subsequent alkene/alkyne Ni-C bond insertion priorities, as well as relevant cycloaddition regioselectivities and kinetics, were investigated using the IDSCRF-B3LYP density functional theory (DFT) method, and all atoms were equitably treated at the DGDZVP level. The results reveal the o-carborane species to be energetically hedged into a four-step path (barrier heights 5.3, 19.7, 18.4 and 0.3 kcal mol-1, respectively) prior to being transferred into the active Ni-carboryne species (COM1) with the assistance of nBuLi and NiCl2(PPh3)2 at room temperature. In direct agreement with empirical trends, alkene insertion into Ni-C bonds on COM1 is exclusively favoured over the competing alkyne insertion. Electronic structure analyses of the corresponding transition structures showed that the preference of alkenes to alkynes is due to different bonding characteristics during this insertion process, namely, back donation for alkenes but donation for alkyne insertion, as evidenced by molecular graphics and NBO charge distributions. Subsequent alkyne additions (i.e. post alkene insertion) arise as the rate-determining step (RDS) for each of the five different reactions (a-e) explored. The solution free-energy barriers of these RDSs (30.5-38.5 kcal mol-1) were in quantitative agreement with their corresponding experimental yields, evidencing the reliability of the DFT results to reproduce chemical phenomena and energetic trends in real Ni-catalysed carboryne-alkene/alkyne cycloadditions.

Four Hybrid Flavan-Chalcones, Caesalpinnone A Possessing a 10,11-Dioxatricyclic [5.3.3.01,6]Tridecane-Bridged System and Caesalpinflavans A-C from Caesalpinia enneaphylla.

Caesalpinnone A (1), an unprecedented hybrid of flavan and chalcone, possessing a 10,11-dioxatricyclic [5.3.3.01,6]tridecane-bridged system, and caesalpinflavans A-C (2-4), three new hybrid flavan-chalcones, were isolated from the twigs and leaves of Caesalpinia enneaphylla. Their structures were elucidated by a combination of spectroscopic analyses and single-crystal X-ray diffraction. Caesalpinnone A showed the highest cytotoxicity against the HL-60, SMMC-7721, A-549, MCF-7, and SW-480 human tumor cell lines with an IC50 in the range of 0.54-0.87 µM.

Multi-Pathway Consequent Chemoselectivities of CpRuCl(PPh3 )2 /MeI-Catalysed Norbornadiene Alkyne Cycloadditions.

Chemoselectivities of five experimentally realised CpRuCl(PPh3 )2 /MeI-catalysed couplings of 7-azabenzo-norbornadienes with selected alkynes were successfully resolved from multiple reaction pathway models. Density functional theory calculations showed the following mechanistic succession to be energetically plausible: (1) CpRuI catalyst activation; (2) formation of crucial metallacyclopentene intermediate; (3) cyclobutene product (P2) elimination (ΔGRel(RDS) ≈11.9-17.6 kcal mol-1 ). Alternative formation of dihydrobenzoindole products (P1) by isomerisation to azametalla-cyclohexene followed by subsequent CpRuI release was much less favourable (ΔGRel(RDS) ≈26.5-29.8 kcal mol-1 ). Emergent stereoselectivities were in close agreement with experimental results for reactions a, b, e. Consequent investigations employing dispersion corrections similarly support the empirical findings of P1 dominating in reactions c and d through P2→P1 product transformations as being probable (ΔG≈25.3-30.1 kcal mol-1 ).

Competing Mechanisms, Substituent Effects, and Regioselectivities of Nickel-Catalyzed [2 + 2 + 2] Cycloaddition between Carboryne and Alkynes: A DFT Study.

Competing reaction mechanisms, substituent effects, and regioselectivities of Ni(PPh3)2-catalyzed [2 + 2 + 2] carboryne-alkyne cycloadditions were characterized by density functional theory using the real chemical systems and solvent effects considered. A putative mechanism involving the following steps was characterized: (1) exothermic carboryne-catalyst complexation and nucleophilic attack by the first alkyne; (2) insertion of the second alkyne, the rate-determining step (RDS) in all four reactions studied; (3) isomerization of reactant-bound complexes; and (4) product elimination and catalyst regeneration. The RDS in three reactions is mediated by free energy barriers of 27.2, 31.1, and 36.6 kcal·mol(-1), representative of the corresponding experimental yields of 67, 54, and 33%, respectively. A fourth reaction with 0% experimental yield showed representative RDS free energy barriers of 60.4 kcal·mol(-1), which are difficult to surmount even at 90 °C. Alternative pathways leading to differing isomers were similarly characterized and successfully reproduced experimentally determined product regioselectivities. Kinetic data derived from free energy barriers are in quantitative agreement (< ± 0.75-3.0 kcal·mol(-1)) of the experimental times, affirming the theoretical results as representative of the real chemical transformations. Complementary determinations show the use of truncated models (Ni(PMe3)2, Ni(PH3)2) causes the RDS to vary from step 2 (alkyne insertion) to step 1 (alkyne attack), highlighting the need to employ real chemical systems in modeling these reactions.

New members of fluorescent 1,8-naphthyridine-based BF2 compounds: selective binding of BF2 with terminal bidentate N

Intensely luminescent 1,8-naphthyridine-BF2 complexes 1-9 containing terminal bidentate N^N^O and/or N^C^O groups are synthesized and structurally characterized by X-ray diffraction, electrospray ionization mass spectrometry, (1)H and (19)F NMR spectroscopy and elemental analysis. Complexes 1-4 are synthesized from 2-acetamino-1,8-naphthyridine derivatives by a facile route. Selective bonding modes and the chemical stability of complexes 5 and 6 obtained by reacting BF3·Et2O with 1,8-naphthyridine derivatives bearing dual-functional groups (N^C^O and N^N^O) are investigated by crystal structure analysis and time-dependent density functional theory calculations. The products containing a BF2 core bound to a N^C^O chelating group are energetically favorable and can expand the range of derivatives by substitution at the 2-position. In this regard, a free -NH2 group at the 2-position of complex 7 obtained from 5 can be functionalized under a variety of pH conditions to generate complexes 8 and 9, which bear flexible coordination arms that can be used to recognize certain transition metals. The photophysical properties of the complexes are examined in solution and solid state at room temperature. Compared with those of the starting naphthyridine-based compounds, the naphthyridine-BF2 complexes display desirable light-absorbing properties and intense solution and solid-state emission with large Stokes shifts. Complex 4 in solution exhibited an emission quantum yield of 0.98. In complexes 5-9, the binding sites for the BF2 core change from N^N^O to N^C^O, which leads to red shifts of absorption and emission, excellent chemical stability and high emission quantum yields.

A new natural naphtho[1,2-b]furan from the leaves of Cassia fistula.

A new naphtho[1,2-b]furan, 2,9-dihydroxy-7-methoxy-4-methylnaphtha[1,2-b]furan-3(2H)-one (1), along with 10 known compounds vanillic acid (2), naringenin (3), glyceryl-1-tetracosanoate (4), moracin J (5), 1,3,8-trihydroxyanthraquinone (6), esculetin (7), mauritianin (8), kaempferol 3-neohesperidoside (9), ß-sitosterol (10), and ß-daucosterol (11), was isolated from the leaves of Cassia fistula. The structure of the new compound was determined by NMR and X-ray analysis. Compounds 1, 3, 5-9 were isolated from this plant for the first time. The naphtha[1,2-b]furan was firstly isolated from the natural resources.

Large Stokes shift induced by intramolcular charge transfer in N,O-chelated naphthyridine-BF2 complexes.

Novel N,O-chelated naphthyridine-BF(2) complexes with push-pull structures have been synthesized and characterized. Spectral investigations on these complexes reveal that photoinduced intramolecular charge transfer occurs and results in a large Stokes shift, which is further supported by density functional theory based theoretical calculations.

Cu(I) and Pb(II) complexes containing new tris(7-naphthyridyl)methane derivatives: synthesis, structures, spectroscopy and geometric conversion.

Two novel facial-capping tris-naphthyridyl compounds, 2-chloro-5-methyl-7-((2,4-dimethyl-1,8-naphthyridin-7(1H)-ylidene)(2,4-dimethyl-1,8-naphthyridin-7-yl))methyl-1,8-naphthyridine (L(1)) and 2-chloro-7-((2-methyl-1,8-naphthyridin-7(1H)-ylidene)(2-methyl-1,8-naphthyridin-7-yl))methyl-1,8-naphthyridine (L(2)), as well as their Cu(i) and Pb(ii) complexes, [CuL(a)(PPh(3))]BF(4) (1) (PPh(3) = triphenylphosphine, L(a) = bis(2,4-dimethyl-1,8-naphthyridin-7-yl)(2-chloro-5-methyl-1,8-naphthyridin-7-yl)methane), [CuL(b)(PPh(3))]BF(4) (2) (L(b) = bis(2-methyl-1,8-naphthyridin-7-yl)(2-chloro-1,8-naphthyridin-7-yl)methane), [Pb(OL(a))(NO(3))(2)] (3) (OL(a) = bis(2,4-dimethyl-1,8-naphthyridin-7-yl)(2-chloro-5-methyl-1,8-naphthyridin-7-yl)methanol) and [Pb(L(b))(2)][Pb(CH(3)OH)(NO(3))(4)] (4), have been synthesized and characterized by X-ray diffraction analysis, MS, NMR and elemental analysis. The structural investigations revealed that the transfer of the H-atom at the central carbon to an adjacent naphthyridine-N atom affords L(1) and L(2) possessing large conjugated architectures, and the central carbon atoms adopt the sp(2) hybridized bonding mode. The reversible hydrogen transfer and a geometric configuration conversion from sp(2) to sp(3) of the central carbon atom were observed when Pb(II) and Cu(I) were coordinated to L(1) or L(2). The molecular energy changes accompanying the hydrogen migration and titration of H(+) to different receptor-N at L(1) were calculated by density functional theory (DFT) at the SCRF-B3LYP/6-311++G(d,p) level in a CH(2)Cl(2) solution, and the observed lowest-energy absorption and emission for L(1) and L(2) can be tentatively assigned to an intramolecular charge transfer (ICT) transition in nature.

Intense one- and two-photon excited fluorescent bis(BF2) core complex containing a 1,8-naphthyridine derivative.

The first bis(BF(2)) core complex containing a 1,8-naphthyridin derivative (1,2-bis(5,7-dimethyl-1,8-naphthyridin-2-yl)hydrazine) and with yellow-green emission as well as a high quantum yield was synthesized and structurally characterized, and the compound exhibits two-photon absorption and excited fluorescence properties.

Synthesis, characterization, photoinduced isomerization, and spectroscopic properties of vinyl-1,8-naphthyridine derivatives and their copper(I) complexes.

A series of 1,8-naphthyridine derivatives containing vinyl, 2-(2-acetylamino-pyridine-6-ethylene)-4-methyl-7-acetylamino-1,8-naphthyridine (L(1)), 2-(2-acetylamino-pyridine-6-ethylene)-1,8-naphthyridine (L(2)), 2-(2-acetylamino-pyridinyl-6-ethylene)-4-methyl-7-hydroxyl-1,8-naphthyridine (L(3)), 2-(2-diacetylamino-pyridinyl-3-ethylene)-7-diacetylamino-1,8-naphthyridine (L(4)), and 7-(2-diacetylamino-pyridinyl-3-ethylene)-4'-acetyl-pyrrolo[1',5'-a]-1,8-naphthyridine (L(5)), as well as complexes [CuL(1)(PCy(3))](BF(4))(2) (1) (PCy(3) = tricyclohexylphosphine), [Cu(2)L(1)(PPh(3))(4)](BF(4))(2) (2) (PPh(3) = triphenylphosphine), [Cu(2)L(1)(dppm)](BF(4))(2) (3) (dppm = bis(diphenylphosphino)methane), and [Cu(2)(L(1))(dcpm)][BF(4)](2) (4) (dcpm = bis(dicyclohexylphosphino)methane, were synthesized. All these compounds, except for L(1) and L(2), were characterized by single crystal X-ray diffraction analysis, and a comprehensive study of their spectroscopic properties involving experimental theoretical studies is presented. We found an intramolecular 1,3-hydrogen transfer during the formation of L(3) and L(4), which in the case of the latter plays an important role in the 1,5-dipolar cyclization of L(5). The spectral changes that originate from an intramolecular charge transfer (ICT) in the form of a pi(py)-->pi*(napy) transition can be tuned through acid/base-controlled switching for L(1)-L(3). A photoinduced isomerization for L(1)-L(3), 1, and 2 having flexible structures was observed under 365 nm light irradiation. Quantum chemical calculations revealed that the dinuclear complexes with structural asymmetry exhibit different metal-to-ligand charge-transfer transitions.

Density functional theory investigation of the alkyl-alkyl Negishi cross-coupling reaction catalyzed by N-heterocyclic carbene (NHC)-Pd complexes.

A novel mechanism is proposed for the Pd-1,3-(2,6-diisopropylphenyl)imidazolyl-2-ylidene (1) catalyzed Negishi reaction. DFT computations supported by atoms-in-molecules (AIM) analyses of non-truncated models show that a "steric wall" created by the N-substituent on the ligand guides reactants to and from the Pd center. Notably, transmetalation and not oxidative addition is found to be rate-limiting. Additionally, a key Pd-Zn interaction (approximately = 2.4 A, rho(b) approximately = 0.0600 au) is identified in the mechanism. This interaction persists beyond reductive elimination and, in combination with the ligand, facilitates reductive elimination by creating a highly sterically crowded environment in the coordination sphere of the Pd center.

High level ab initio exploration on the conversion of carbon dioxide into oxazolidinones: the mechanism and regioselectivity.

Density functional theory (DFT) and second order Møller-Plesset perturbation (MP2) calculations, employing the 6-311++G(d,p) basis set, were carried out on alkyl-substituted aziridines to explore the reaction mechanisms and regioselectivity associated with their ring-opening conversions to oxazolidinones, in the presence of carbon dioxide. Computational results, employing the self-consistent reaction field polarizable continuum model (SCRF(PCM/Bader)), indicated that the conversions proceed with thermodynamic ease in THF solvent at room temperature. It is proposed that the N-alkylaziridine promotes ring opening through a SN2 attack of the iodide ion, of catalytic lithium iodide, on the preformed complex. The oxazolidinone regioisomer ratio is highly sensitive to aziridine ring-carbon substitution. Therein, monophenyl substitutions show preference to opening more highly substituted carbon-nitrogen bonds, providing rationale as to why experimental works result in an exclusive oxazolidinone regioisomer product.

Hydrothermal reaction of Cu(II)/pyrazine-2,3,5-tricarboxylic acid and characterization of the copper(II) complexes.

Four copper(II) complexes [Cu3(PZHD)2(2,2'-bpy)2(H2O)2].3H2O (1), [Cu3(DHPZA)2(2,2'-bpy)2] (2), [Cu(C2O4)phen(H2O)].H2O (3), and [Cu3(PZTC)2(2,2'-bpy)2].2H2O (4) were synthesized by hydrothermal reactions, in which the complexes 1-3 were obtained by the in situ Cu(II)/H3PZTC reactions (PZHD3- = 2-hydroxypyrazine-3,5-dicarboxylate, 2,2'-bpy = 2,2'-bipyridine, DHPZA3- = 2,3-dihydroxypyrazine-5-carboxylate, C2O42- = oxalate, phen = 1,10-phenanthroline, and H3PZTC = pyrazine-2,3,5-tricarboxylic acid). The Cu(II)/H3PZTC hydrothermal reaction with 2,2'-bpy, without addition of NaOH, results in the formation of complex 4. The complexes 1-4 and transformations from H3PZTC to PZHD3-, DHPZA3-, and C2O4(2-) were characterized by single-crystal X-ray diffraction and theoretical calculations. In the complexes 1, 2, and 4, the ligands PZHD3-, DPHZA3-, and PZTC3- all show pentadentate coordination to Cu(II) ion forming three different trinuclear units. The trinuclear units in 1 are assembled by hydrogen-bonding and pi-pi stacking to form a 3D supramolecular network. The trinuclear units in 2 acting as building blocks are connected by the carboxylate oxygen atoms forming a 2D metal-organic framework (MOF) with (4,4) topology. While the trinuclear units in 4 are linked together by the carboxylate oxygen atoms to form a novel 2D MOF containing right- and left-handed helical chains. The theoretical characterization testifies that electron transfer between OH- and Cu2+ and redox of Cu 2+ and Cu+ are the most important processes involved in the in situ copper Cu(II)/H3PZTC reactions, forming complexes of 1-3.