Realistic modelling of hydrogen bonding of 2-cyclohexenone with H2O and H3BO3 in the outer coordination sphere of a chiral diene/Rh(I) complex by ab initio molecular dynamics.

A full-DFT Born-Openheimer MD (BOMD) study of the potential hydrogen bonding of 2-cyclohexenone π-complexed to Rh(I) in explicit 1,4-dioxane is presented. The complex is a key intermediate in the academically and industrially important asymmetric Rh-catalysed 1,4-addition of arylboronic acids to α,ß-unsaturated ketones with the directing ligand phbod, a chiral bicyclic 1,4-diene. The ketone O atom (Ok) behaves as a single H-bond acceptor persistently throughout most of the simulation time while the donor is mobile and liable to exchange. Well-tempered metadynamics show that H-bonding with a (H2O)3 cluster is favorable by free energy but kinetically labile while with just H3BO3 is unfavorable but kinetically much more persistent. When both (H2O)3 cluster and H3BO3 are within H-bond distance from Ok, the non-H-bonded and the various H-bonded species are close in energy, implying the free energy surface is complex and quite flat. The most stable species features a H-bond with a water acceptor but not with H3BO3. The non-H-bonded state is 0.7 kcal mol-1 higher in free energy. Model static DFT studies reveal that H-bonding with both (H2O)3 cluster and H3BO3 is favorable by enthalpy, but unfavorable by free energy when the entropy term is added.

Characterization of the RhI /dppe-Catalyzed Ring Expansion of 2-Alkyl-Benzocyclobutenones by DFT Calculations.

The [(dppe)RhCl]-catalysed ring expansion of 2-methylbenzocyclobutenone has been proposed to occur by C-C oxidative addition to rhodaindanone, ß-hydride elimination, hydrorhodation and C-C reductive elimination. DFT calculations [IEFPCM(1,4-dioxane, 383.15 K)/PBE0/DGDZVP level of theory] here confirm this mechanism. As proposed, oxidative addition into CHMe-CO bond is preferred over the alternative CHMe-aryl insertion. The barriers of oxidative addition, ß-hydride elimination hydrorhodation, and reductive elimination are 23.6 (rate-determining), 8.9, 10.4, and 13.1 kcal mol-1 , respectively. Therefore, the ß-hydride elimination/hydrorhodation steps to/from an octahedral RhIII -hydride serve as a fast equilibrating hydrogen shuffle flanking the two slower C-C bond breaking/making steps. This is consistent with the weak kinetic isotope effect observed experimentally when 2-CH3 and 2-CD3 benzocyclobutenone react competitively in a 1:1 ratio. The reaction barriers calculated with more modern, dispersion interaction-corrected methods (SMD/M06 and IEFPCM/ωB97xD) follow identical trends.

A Bulky Disulfoxide Ligand for Pd-Catalyzed Oxidative Allylic C-H Amination with 2,2,2-Trichloroethyl Tosyl Carbamate.

Challenging substrates and conditions in homogeneous catalysis pose stringent demands on the ligands used. A novel, bulky, 1-adamantyl-substituted disulfoxide ligand designed after a systematic evaluation of the electronic and steric properties of disulfoxide substituents permits the allylic oxidative C-N coupling reaction to proceed at lower catalyst loading while requiring a smaller excess of reagents. Additionally, this ligand improves the yields when TsNHCOOCH2CCl3, a novel reagent that permits deprotection of the products under both acidic and basic conditions, is used.

Cooperativity of axial and centre chirality in the biaryl disulfoxide/Rh(i)-catalysed asymmetric 1,4-addition of arylboronic aids to 2-cyclohexenone: a DFT study.

Atropisomeric biaryl disulfoxides contain two independent chiral elements. Previously, the (M,S,S)-diastereomer showed very high catalytic activity and selectivity in the Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,ß-enones whereas the (M,R,R) counterpart - none. Herein, DFT computations on the key transmetallation (turnover-determining) and carborhodation (enantioselectivity-determining) steps of the catalytic cycle show that the (M,S,S)-ligand gives rise to lower reaction barriers for these elementary steps. However, the barriers for the (M,R,R)-ligand are not sufficiently high to explain the lack of reactivity. Hence, this phenomenon is most likely due to the failure of catalyst formation from the ligand and the dimeric Rh precatalyst complex. The hitherto unknown (M,S,R)-ligand shows predicted enantioselectivity similar to the (M,S,S)-ligand as a consequence of lower reaction barriers associated with those isomers whose key features resemble the (M,S,S)-ligand.

Copper-Catalyzed Regioselective 1,2-Alkylesterification of Dienes to Allylic Esters.

Copper catalyzed 1,2-alkylesterification of 1,3-dienes with diacyl peroxides affords branched allylic esters in excellent regioselectivity, including products with a newly generated fully substituted carbon center. The only byproduct is CO2. The reaction proceeds by a radical mechanism as suggested by spin trap and crossover experiments.

The challenge of linear (E)-enones in the Rh-catalyzed, asymmetric 1,4-addition reaction of phenylboronic acid: a DFT computational analysis.

Why are linear (E)-enones such challenging substrates in the Rh-catalyzed asymmetric arylation with boronic acids, which is one of the most important asymmetric catalysis methods? DFT computations show that these substrates adopt a specific conformation in which the largest substituent is antiperiplanar to Rh(I) π-complexed with the C = C bond within the enantioselectivity-determining carborhodation transition state. Additionally, for such structures, there is a strong, but not exclusive, preference for s-cis enone conformation. This folding minimizes steric interactions between the substrate and the ligand, and hence reduces the enantioselectivity. This idea is further confirmed by investigating three computation-only substrate "probes", one of which is capable of double asymmetric induction, and a recent computationally designed 1,5-diene ligand. On average, excellent agreement between predicted and experimental enantioselectivity was attained by a three-pronged approach: 1) thorough conformational search within ligand and substrate subunits to locate the most preferred carborhodation transition state; 2) including dispersion interaction and long-range corrections by SMD/ωB97xD/DGDZVP level of theory; and 3) full substrate and ligand modeling. Based on the results, a theory-enhanced enantioselectivity model that is applicable to both chiral diene and diphosphane ligands is proposed.

Transmetalation from B to Rh in the course of the catalytic asymmetric 1,4-addition reaction of phenylboronic acid to enones: a computational comparison of diphosphane and diene ligands.

Transmetalation is a key elementary reaction of many important catalytic reactions. Among these, 1,4-addition of arylboronic acids to organic acceptors such as α,ß-unsaturated ketones has emerged as one of the most important methods for asymmetric C-C bond formation. A key intermediate for the B-to-Rh transfer arising from quaternization on a boronic acid by a Rh-bound hydroxide (the active catalyst) has been proposed. Herein, DFT calculations (IEFPCM/PBE0/DGDZVP level of theory) establish the viability of this proposal, and characterize the associated pathways. The delivery of phenylboronic acid in the orientation suited for the B-to-Rh transfer from the very beginning is energetically preferable, and occurs with expulsion of Rh-coordinated water molecules. For the bulkier binap ligand, the barriers are higher (particularly for the phenylboronic acid activation step) due to a less favourable entropy term to the free energy, in accordance with the experimentally observed slower transmetalation rate.

DFT computations support the σ-complex assisted metathesis (σ-CAM) mechanism for the 1,4-Rh shift of Cp*Rh(III)-(η(1)-ß-styryl) complexes.

DFT calculations support the σ-complex assisted metathesis (σ-CAM) mechanism recently proposed for the first 1,4-Rh shift of a Rh(III) complex rather than the oxidative addition/reductive elimination pathway characteristic of Rh(i). A single, concerted TS (ΔG(‡) = 27-34 kcal mol(-1)) was found and its electronic structure characterized by Bader's AIM analysis. The 4-centered TS is characterized by a enhanced charge separation (Rh and H atoms - positive, both C atoms - negative) relative to the σ-vinyl Rh starting material and the σ-aryl-Rh product. The AIM topological analysis of the electron density reveals a network of interactions: Rh with H as well as both Rh and H with both C(vinyl) and C(aryl) in the TS and confirms the C(vinyl)-Rh agnostic interaction observed experimentally in the σ-aryl-Rh product.

First principles (DFT) characterization of Rh(I) /dppp-catalyzed C-H activation by tandem 1,2-addition/1,4-Rh shift reactions of norbornene to phenylboronic acid.

The C-H activation in the tandem, "merry-go-round", [(dppp)Rh]-catalyzed (dppp=1,3-bis(diphenylphosphino)propane), four-fold addition of norborene to PhB(OH)2 has been postulated to occur by a C(alkyl)H oxidative addition to square-pyramidal Rh(III) -H species, which in turn undergoes a C(aryl)-H reductive elimination. Our DFT calculations confirm the Rh(I) /Rh(III) mechanism. At the IEFPCM(toluene, 373.15 K)/PBE0/DGDZVP level of theory, the oxidative addition barrier was calculated to be 12.9 kcal mol(-1) , and that of reductive elimination was 5.0 kcal mol(-1) . The observed selectivity of the reaction correlates well with the relative energy barriers of the cycle steps. The higher barrier (20.9 kcal mol(-1) ) for norbornyl-Rh protonation ensures that the reaction is steered towards the 1,4-shift (total barrier of 16.3 kcal mol(-1) ), acting as an equilibration shuttle. The carborhodation (13.2 kcal mol(-1) ) proceeds through a lower barrier than the protonation (16.7 kcal mol(-1) ) of the rearranged aryl-Rh species in the absence of o- or m-substituents, ensuring multiple carborhodations take place. However, for 2,5-dimethylphenyl, which was used as a model substrate, the barrier for carborhodation is increased to 19.4 kcal mol(-1) , explaining the observed termination of the reaction at 1,2,3,4-tetra(exo-norborn-2-yl)benzene. Finally, calculations with (Z)-2-butene gave a carborhodation barrier of 20.2 kcal mol(-1) , suggesting that carborhodation of non-strained, open-chain substrates would be disfavored relative to protonation.

A first-principles examination of the asymmetric induction model in the binap/Rh(I)-catalysed 1,4-addition of phenylboronic acid to cyclic enones by density functional theory calculations.

First-principles modelling of the diastereomeric transition states in the enantiodiscrimination stage of the catalytic cycle can reveal intimate details about the mechanism of enantioselection. This information can be invaluable for further improvement of the catalytic protocols by rational design. Herein, we present a density functional theory (IEFPCM/PBE0/DGDZVP level of theory) modelling of the carborhodation step for the asymmetric 1,4-arylation of cyclic α,ß-unsaturated ketones mediated by a [(binap)Rh(I)] catalyst. The calculations completely support the older, qualitative, pictorial model predicting the sense of the asymmetric induction for both the chelating diphosphane (binap) and the more recent chiral diene (Phbod) ligands, while also permitting quantification of the enantiomeric excess (ee). The effect of dispersion interaction correction and basis sets has been also investigated. Dispersion-corrected functionals and solvation models significantly improve the predicted ee values.

Time-dependent density functional theory (TDDFT) modelling of Pechmann dyes: from accurate absorption maximum prediction to virtual dye screening.

The red Pechmann dye (λ(max) = 550 nm) is the exo-dimer of 4-phenyl-3-butenolide connected at the α-carbon by a double bond in a trans-fashion. The ring system is easily rearranged to the trans-endo-fused bicyclic 6-membered lactone dimer (yellow). Both lactones can be singly or doubly amidated with primary amines leading to further colour changes. The nature of the core heterocycle (exo- vs. endo-; 5- or 6-membered ring), core heteroatom (O vs. N) and additional substituents on the phenyl ring allows for exquisite control over colour achievable within a single dye family. Herein we present a detailed investigation of the modelling of the electronic spectra of the Pechmann dye family by time-dependent density functional theory (TDDFT). Whereas pure Hartree-Fock (TDHF) ab-initio calculation underestimates the UV/Vis absorption maximum, pure TDDFT leads to a large overestimation. The accuracy of the prediction is highly dependent on the mix of HF and DFT, with BMK (42% HF) and M06-2X (54% HF) giving the closest match with the experimental value. Among all basis sets evaluated, the computationally-efficient, DFT-optimized DGDZVP showed the best chemical accuracy/size profile. Finally, the dispersion interaction-corrected (SMD) implicit solvation model was found to be advantageous compared to the original IEFPCM. The absorption maxima of substituted Pechmann dyes and their rearranged lactone counterparts can be predicted with excellent accuracy (±6 nm) at the optimal SMD(toluene)/TD-BMK/DGDZVP//SMD(toluene)B3LYP/DGDZVP level of theory. Using this procedure, a small virtual library of novel, heterocycle-substituted Pechmann dyes were screened. Such substitution was shown to be a viable strategy for colour tuning, giving λ(max) from 522 (4-pyridyl) to 627 (2-indolyl) nm.

Tunable, dynamic and electrically stimulated lectin-carbohydrate recognition on a glycan-grafted conjugated polymer.

An electroactive platform for multivalent, reversible and electrically stimulated lectin-carbohydrate recognition based on mannose-functionalized conjugated polymer is reported and tuned by electrocopolymerization of mixture of tri(ethylene glycol)-functionalized EDOT and its α-mannose conjugate.

Thiophene-containing Pechmann dyes and related compounds: synthesis, and experimental and DFT characterisation.

Attaching 2-thienyl residues to the Pechmann dye core chromophore (5,5-exo-dilactone situated around a C-C double bond) results in a novel magenta-coloured compound (UV/Vis spectroscopy λ(max) =570 nm in CHCl(3)), which can be rearranged to a yellow 6,6-endo-dilactone (λ(max) =462 nm in CHCl(3)). Single and double amidation results in pronounced redshift in the 5,5-exo series (violet, λ(max) =570 nm and blue, λ(max) =606 nm in CHCl(3), respectively) but pronounced blueshift in the 6,6-endo series (yellow, λ(max) =424 nm and pale yellow bordering on colourless, λ(max) =395 nm in CHCl(3), respectively). Incorporation of a 3-alkyl substituent on the thiophene ring allows for sharp increase of solubility in organic solvents concomitant with fine-tuning of the colour: a redshift in 5,5-exo-dilactones but a blueshift in 5,5-exo-dilactams. DFT computations demonstrate that both lactone classes are planar regardless of the presence of a 3-alkyl group. The lactam derivatives are non-planar: the thiophene-core chromophore dihedral angles increase on going from 5,5-exo to 6,6-endo and from thiophene to 3-alkyl thiophene. Depending on the core heteroatom (O vs. N-alkyl), ring junction (5,5-exo vs. 6,6-endo) and 3-thiophene substituent (H vs. alkyl), two, three, four or six conformers are possible. All of these conformers were characterised by DFT and were found to be very close in energy at both IEFPCM/B3LYP/DGDZVP and SMD/M06/DGDZVP levels of theory. Within each conformer set, the HOMO and LUMO energies were within 0.05 eV and the predicted λ(max) values (TD-DFT) within 10 nm, and this implies low sensitivity of the optical and electronic properties to conformation. Cyclic voltammetry measurements of selected compounds demonstrated good matching to the HOMO and LUMO energies from IEFPCM/B3LYP/DGDZVP computations. M06-2X was the best DFT functional for TD-DFT, giving predicted λ(max) values within about 20 nm.

O,O'-Disubstituted N,N'-dihydroxynaphthalenediimides (DHNDI): first principles designed organic building blocks for materials science.

N,N'-Disubstituted naphthalenediimides (NDIs), planar, electron-deficient building blocks, play an important role in materials and biological sciences. Naphthalene core substituents control the HOMO and LUMO energies, whereas the N-alkyl or aryl substituents affect the solubility, aggregation, and packing propensity in condensed phases. N,N'-Dihydroxynaphthalenediimide (DHNDI) allows expanding the chemical diversity by O-alkylation, acylation, or sulfonylation; these derivatives also allow fine-tuning of the HOMO/LUMO levels. The synthesis, UV-vis, electrochemical, solid state, and computational prediction of the properties of such derivatives are presented.

The origin of regio- and enantioselectivity in the Rh/chiral 1,4-diene-catalyzed addition of phenylboronic acid to enones: insights from DFT.

A density functional theory study of the addition of phenylboronic acid to cyclohexenone catalyzed by chiral 1,4-diene-Rh(I) catalyst reveals that 1,4-addition is thermodynamically preferred. The enthalpy-driven enantioselection occurs during the carborhodation step and not the enone binding step, as previously proposed. The chiral ligand selectively destabilizes the disfavored transition state by making it "more early".

Electropolymerization of intercalator-grafted conducting polymer for direct and amplified DNA detection.

Efficient DNA intercalators comprising naphthalene diimide grafted with ethylenedioxythiophene monomer were successfully designed, synthesized and applied to mediate/promote conducting polymer growth electrochemically on biosensor electrodes for direct and amplified DNA detection.

Thiophene-containing Pechmann dye derivatives.

Thiophene-containing Pechmann dyes (unsaturated exo-5,5-dilactones) were easily prepared by Cu-catalyzed dehydration of the corresponding ß-aroylacrylic acids. Introduction of long alkyl chains greatly enhances solubility. Isomerization of an alkyl-substituted thiophene Pechmann dye (TPD) gave the corresponding endo-6,6-dilactone. The redox and electronic properties of these new dyes were investigated by CV, UV/vis, and fluorescence spectroscopy and DFT and TD-DFT computations. Strong absorption and emission in the visible region were recorded.

Structure-activity relationship analysis of Pd-PEPPSI complexes in cross-couplings: a close inspection of the catalytic cycle and the precatalyst activation model.

A series of Pd-N-heterocyclic carbene (Pd-NHC) complexes with various NHC, halide and pyridine ligands (PEPPSI (pyridine, enhanced, precatalyst, preparation, stabilisation and initiation) precatalysts) were prepared, and the effects of these ligands on catalyst activation and performance were studied in the Kumada-Tamao-Corriu (KTC), Negishi, and Suzuki-Miyaura cross-coupling reactions. The lowered reactivity of more hindered 2,6-dimethylpyridyl complex 4 in the Negishi and KTC reactions is consistent with slow reductive dimerisation of the organometallic reaction partner during precatalyst activation. Comparative rate studies of complexes 1, 4 and 5 in the KTC and Suzuki-Miyaura reactions verify that 4 activated more slowly than the others. A potential on/off mechanism of pyridine coordination to NHC-Pd(0) is also plausible, in which the more basic pyridine stays bound for longer.

The fine balance between one cross-coupling and two beta-hydride elimination pathways: a DFT mechanistic study of Ni(pi-allyl)(2)-catalyzed cross-coupling of alkyl halides and alkyl Grignard reagents.

The model cross-coupling of EtBr with EtMgCl mediated by Ni(pi-allyl)(2) proceeds by a catalytic cycle commencing with transmetalation establishing a novel Mg-allyl interaction, followed by Mg-assisted oxidative addition (the rate-determining step), followed by reductive elimination having much lower barrier than 2 competing beta-hydride elimination pathways, and completed by departure of MgBrCl.

Rational exploration of N-heterocyclic carbene (NHC) palladacycle diversity: a highly active and versatile precatalyst for Suzuki-Miyaura coupling reactions of deactivated aryl and alkyl substrates.

As less attention has been focussed on the design of highly efficient palladium precatalysts to ensure the smooth formation of the active catalyst for metal-mediated cross coupling reactions, we herein demonstrate that combining the bulky N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) with cyclopalladated acetanilide as the optimal palladium precatalyst leads to superior catalytic activity compared with the state-of-the-art NHC-Pd catalysts. The complex was discovered through the evaluation of a small, rationally designed library of NHC-palladacycles prepared by a novel, practical and atom-economic method, the direct reaction of IPrHCl with palladacycle acetate dimers.