Steric Effects Of Substituents Research Articles

Tuning the Stability and Kinetics of Dioxazaborocanes.

We investigated the equilibrium reaction of boronic acid (BA), diethanolamines (DEA), and 1,3,6,2-dioxazaborocanes (DOAB) in aqueous solutions, both theoretically and experimentally. Our findings show that the association constant can be adjusted by substituting BA and DEA derivatives, ranging from 100 to 103 M-1, exhibiting a bell-shaped pH dependency. The highest stability was achieved when the pKa values of DEA and BA were closely matched. This approach enabled the preparation of a highly stable DOAB under physiological conditions. Furthermore, the hydrolysis kinetics of DOABs were controllable over a range of five orders of magnitude based on the substituent's steric effect. In the slowest case, this resulted in quasi-static stability with only 1% cleavage in the first hour, followed by a week-long cleavage period to reach equilibrium. These insights could establish a unique chemistry platform for designing scheduled cleavability on a day-to-week timescale, relevant to protein engineering, immunotherapy, and other smart drug delivery applications.

Self-Assembly of Thienopyrrole-Fused Thiadiazoles Containing an Amide Linker: Control of Supramolecular Polymerization Mechanism and Chiroptical Properties by Trialkoxy Side Chains.

Three thienopyrrole-fused thiadiazole (TPT) fluorescent dyes featuring a common amide linker and different alkoxy substituents on peripheral trialkoxybenzene moieties were synthesized, and their self-assembly behavior in solution was investigated. The obtained results revealed a substantial steric effect of the alkoxy substituents on the supramolecular polymerization mechanism, which results from a combination of π-stacking and hydrogen (H)-bonding interactions. Detailed spectroscopic measurements revealed that with increasing steric demand of the substituents, the supramolecular polymerization processes in pure methylcyclohexane (MCH) or a mixture of MCH and toluene become temperature-sensitive and enthalpically favorable, resulting in a change from the isodesmic assembly mechanism to the cooperative mechanism. Theoretical calculations suggested that in TPTs with bulky substituents, steric hindrance causes the H-bonding array of the amide moieties to be aligned along the stacking axis of the π-systems; thus, the H-bonding interactions are strengthened compared to those in TPTs with less bulky substituents, compensating for the weakened π-stacking interactions. A chiral TPT derivative with (S) stereogenic centers was found to form homochiral helical supramolecular assemblies that generate discernible circularly polarized luminescence. Achiral TPTs also generate helical assemblies to which preferential helicity can be imparted through the external chiral bias of the solvents (R)- and (S)-limonene.

Catalytic Activity of 2-Imino-1,10-phenthrolyl Fe/Co Complexes via Linear Machine Learning.

In anticipation of the correlations between catalyst structures and their properties, the catalytic activities of 2-imino-1,10-phenanthrolyl iron and cobalt metal complexes are quantitatively investigated via linear machine learning (ML) algorithms. Comparatively, the Ridge Regression (RR) model has captured more robust predictive performance compared with other linear algorithms, with a correlation coefficient value of R2= 0.952 and a cross-validation value of Q2= 0.871. It shows that different algorithms select distinct types of descriptors, depending on the importance of descriptors. Through the interpretation of the RR model, the catalytic activity is potentially related to the steric effect of substituents and negative charged groups. This study refines descriptor selection for accurate modeling, providing insights into the variation principle of catalytic activity.

Nickel‐ and Palladium‐Catalyzed Copolymerizations of Norbornene with Polar α‐Olefins

AbstractRecent progress regarding the copolymerization of norbornene with various polar α‐olefins catalyzed by nickel and palladium catalysts is reviewed here with special attention paid to the diverse catalyst frameworks, polar monomer scopes as well as polymer microstructures. Both the influences of steric effect and electron property of ligand substituents and the type of polar monomers on the catalytic behaviors (activity, stability, polarity tolerance, etc.) and the polymer microstructures (molecular weight and distribution, comonomer contents, etc.) have been summarized. The introduction of noncyclic‐olefins, such as polar vinyl monomers, polar higher α‐olefins, and polar styrenes, into rigid cyclic‐based polynorbornene chain resulted in significant modifications on the polarity, compatibility, thermostability, processibility, transparency, and many other properties of the material, which has also been discussed in the review. The contents of this review have been classified according to the type of polar monomers involved in the norbornene copolymerization, and each section included nickel and palladium catalysts bearing different ligand structures, which will be meaningful for the development of new types of catalysts and new families of norbornene‐based cyclic olefin copolymer materials in the future.

Ethylene/Polar Monomer Copolymerization by [N, P] Ti Complexes: Polar Copolymers with Ultrahigh-Molecular Weight.

A series of novel titanium complexes (2a-2e) bearing [N, P] aniline-chlorodiphenylphosphine ligands (1a-1e) featuring CH3 and F substituents have been synthesized and characterized. Surprisingly, in the presence of polar additive, the complexes (2a-2e) all displayed high catalytic activities (up to 1.04 × 106 gPolymer (mol·Ti)-1·h-1 and produced copolymer with the ultrahigh molecular weight up to 1.37 × 106 g/mol. The catalytic activities are significantly enhanced by introducing electron-withdrawing group (F) into the aniline aromatic ring. Especially, the increase in activity based on different complexes followed the order of 2e > 2d > 2c > 2b > 2a. Simultaneously, density functional theory (DFT) calculations have been performed to probe the polymerization mechanism as well as the electronic and steric effects of various substituents on the catalyst backbone. DFT computation revealed that the polymerization behaviors could be adjusted by the electronic effect of ligand substituents; however, it has little to do with the steric hindrance of the substituents. Furthermore, theoretical calculation results keep well in accordance with experimental measurement results. The article provided an appealing design method that the employment of fluorine atom as electron-withdrawing to be studied is the promotive effect of transition-metal coordination polymerization.

Substituent effects on the selectivity of ambimodal [6+4]/[4+2] cycloaddition.

In this work, we report a density functional theory (DFT) study and a dynamical trajectory study of substituent effects on the ambimodal [6+4]/[4+2] cycloaddition proposed for 1,3,5,10,12-cycloheptadecapentaene, referred to as cycloheptadecapentaene. The proposed cycloaddition proceeds through an ambimodal transition state, which results in both a [6+4] adduct a [4+2] adduct directly. The [6+4] adduct can be readily converted to the [4+2] adduct via a Cope rearrangement. We study the selectivity of the reaction with regard to the position of substituents, steric effects of substituents, and electronic effects of substituents. In the dynamical trajectory study, we find that nitro-substituted reactants lead to a new product from the ambimodal transition state via the hetero Diels-Alder reaction, and this new product can then be converted to a [4+2] adduct by a hetero [3, 3]-sigmatropic rearrangement. These results may provide insights for designing more bridged heterocyclic compounds.

Tuning N-heterocyclic carbene wingtips to form electrochemically stable adlayers on metals.

Self-assembled monolayers (SAMs) are employed in electrochemical biosensors to passivate and functionalize electrode surfaces. These monolayers prevent the occurrence of undesired electrochemical reactions and act as scaffolds for coupling bioaffinity reagents. Thiols are the most common adlayer used for this application; however, the thiol-gold bond is susceptible to competitive displacement by naturally occurring solvated thiols in biological fluids, as well as to desorption under continuous voltage interrogation. To overcome these issues, N-heterocyclic carbene (NHC) monolayers have been proposed as an alternative for electrochemical biosensor applications due to the strong carbon-gold bond. To maximize the effectiveness of NHCs for SAMs, a thorough understanding of both the steric effects of wingtip substituents and NHC precursor type to the passivation of electrode surfaces is required. In this study, five different NHC wingtips as well as two kinds of NHC precursors were evaluated. The best performing NHC adlayers can be cycled continuously for four days (over 30 000 voltammetric cycles) without appreciably desorbing from the electrode surface. Benchmark thiol monolayers, in contrast, rapidly desorb after only twelve hours. Investigations also show NHC adlayer formation on other biosensor-relevant electrodes such as platinum and palladium.

Systematic investigations of ortho-aryl substitution effect on chain microstructure in nickel-catalyzed long chain α-olefin polymerization and copolymerization with methyl undecenoate

The tuning of branching density and branch-type distribution of the polyolefin through the ligand modification in “chain-walking”-type late transition metal catalysts is highly desired but remains a significant challenge in olefin polymerization. Herein, we performed a systematic investigation on the (co)polymerization of long chain α-olefin (1-octene and 1-decene) by a series of α-diimine Ni(II) catalysts with the varied ligand sterics arising from the number of the ortho-aryl (4-methylphenyl) substituents. The effects of structural variations, mainly including the steric tuning on the ortho-position of N-aryl ring and ligand backbone, steric distribution (ligand symmetry) tuning and electronic tuning, and polymerization conditions on catalytic activities, polymer molecular weight, polymer branching density, and branch-type distribution were described. The steric effect of ortho-methylphenyl substituents played a major role rather than the electronic effect in determining the preference of insertion fashion (1,2-insertion or 2,1-insertion) and chain walking in long chain α-olefin polymerization. As the bulk and number of ortho-methylphenyl substituents increased, the preferred 2,1-insertion and 1, ω-enchainment (chain straightening) were observed even at high monomer concentrations, thus leading to the decrease of branching density as well as the percentage of methyl branches, and eventually affording the semicrystalline “polyethylene-like” polymer with high Tm up to 121 °C and good mechanical properties. Moreover, the tuning of chain microstructure can be achieved over a very wide range through the modification of ligand sterics. Most importantly, these Ni(II) catalysts could copolymerize long chain α-olefin and polar monomer methyl undecenoate (MU) to generate the various functionalized semicrystalline copolymers with high incorporation ratios of MU up to 11% and Tm in a wide range of 5.6–93 °C.

Electronic and steric substituent effects on the fluorescence emission of 2-pyrazoline derivatives.

A series of substituted 2-pyrazolines were synthesized, and the steric and electronic effects of substituents on the C3 - and C5 -positions of the heterocyclic ring on their fluorescent ability were investigated. Two different conjugative intramolecular charge transfer (ICT) and intramolecular charge transfer through space (spiro-conjugation) affect the fluorescence intensity of these compounds. The extent of the ICT process and spiro-conjugation depends on the electronic nature of the additional substitution and its position on the attached aryl rings. In addition, the effects of the concentration and the solvent polarity on the fluorescence emission were studied. Density functional theory (DFT) calculations were carried out to gain insight into the geometric, electronic, and spectroscopic properties of the pyrazoline derivatives. The results of both experimental and computational studies explain the effects of the geometrical orientation of the C3 - and C5 -aryl rings toward the heterocyclic ring and also the electronic nature of their additional substitutions on the fluorescence intensity.

A new method for determining the intrinsic resistance energy of H‐atom transfer reaction and structure–activity relationship of H‐donating ability

AbstractThe intrinsic resistance energy ΔG≠XH/X of H‐donor XH in hydrogen atom transfer (HAT) reaction is usually used to evaluate the kinetic H‐donating ability. In this article, a new method for determining ΔG≠XH/X of H‐donor in HAT reaction was proposed by the definition of thermo‐kinetic parameter ΔG≠o (XH) = 1/2[ΔG≠XH/X + ΔGo (XH)]. ΔG≠o (XH) is the characteristic physical parameter of XH to describe the H‐donating ability in a chemical reaction during a certain reaction time, ΔGo (XH) is the bond dissociation free energy. The kinetic studies of HATs between 20 alcohols, ethers, alkanes and amines (XH) with cumyloxyl radical [PhC (CH3)2O•, CumO•] were researched, and ΔGo (XH), ΔG≠XH/X, and ΔG≠o (XH) were used to investigate the H‐donating abilities of the studied substrates in thermodynamics, kinetics, and HAT reaction. The effect of structures of XH on these three parameters, the structure–activity relationship, such as the influence of electronic, steric, polar and stereoelectronic effects of substituents, heteroatoms insertion in cycloalkanes, and cis–trans configurational isomerism on the H‐donating abilities were discussed in detail. This study not only provides a new method for determining ΔG≠XH/X but also systematically studies the factors affecting the H‐donating ability, laying a foundation for the selection, design, and synthesis of more efficient antioxidants.

Schlenk-Type Equilibria of Grignard-Analogous Arylberyllium Complexes: Steric Effects.

The presence of complex Schlenk equilibria is a central property of synthetically invaluable Grignard reagents substantially affecting their reactivity and selectivity in chemical transformations. In this work, the steric effects of aryl substituents on the Schlenk-type equilibria of their lighter congeners, arylberyllium bromides, are systematically studied. Combination of diarylberyllium complexes Ar2 Be(OEt2 ) (1Ar, Ar=Tip, Tcpp; Tip=2,4,6-iPr3 C6 H3 , Tcpp=2,4,6-Cyp3 C6 H3 , Cyp=c-C5 H9 ), containing sterically demanding aryl groups, and BeBr2 (OEt2 )2 (2) affords the Grignard-analogous arylberyllium bromides ArBeBr(OEt2 ) (3Ar, Ar=Tip, Tcpp). In contrast, Mes2 Be(OEt2 ) (1Mes, Mes=2,4,6-Me3 C6 H3 ) and 2 exist in a temperature-dependent equilibrium with MesBeBr(OEt2 ) (3Mes) and free OEt2 . Ph2 Be(OEt2 ) (1Ph) reacts with 2 to afford dimeric [PhBeBr(OEt2 )]2 ([3Ph]2 ). Moreover, the influence of replacing the OEt2 donor by an N-heterocyclic carbene, IPr2 Me2 (IPr2 Me2 =C(iPrNCMe)2 ), on the redistribution reactions was investigated. The solution- and solid-state structures of the diarylberyllium and arylberyllium bromide complexes were comprehensively characterized using multinuclear (1 H, 9 Be, 13 C) NMR spectroscopic methods and single-crystal X-ray diffraction, while DFT calculations were employed to support the experimental findings.

Computational Insights into the Influence of Ligands on Hydrogen Generation with [Cp*Rh] Hydrides.

This work reports a computational investigation of the effect of ancillary ligands on the activity of an Rh catalyst for hydrogen evolution based on the [Cp*Rh] motif (Cp* = η5-pentamethylcyclopentadienyl). Specifically, we investigate why a bipyridyl (bpy) ligand leads to H2 generation but diphenylphosphino-based (dpp) ligands do not. We compare the full ligands to simplified models and systematically vary structural features to ascertain their effect on the reaction energy of each catalytic step. The calculations based on density functional theory show that the main effect on reactivity is the choice of linker atom, followed by its coordination. In particular, P stabilizes the intermediate Rh-hydride species by donating electron density to the Rh, thus inhibiting the reaction toward H2 generation. Conversely, N, a more electron-withdrawing center, favors H2 generation at the price of destabilizing the hydride intermediate, which cannot be isolated experimentally and makes determining the mechanism of this reaction more difficult. We also find that the steric effects of bulky substituents on the main ligand scaffold can lead to large effects on the reactivity, which may be challenging to fine-tune. On the other hand, structural features like the bite angle of the bidentate ligand have a much smaller impact on reactivity. Therefore, we propose that the choice of linker atom is key for the catalytic activity of this species, which can be further fine-tuned by a proper choice of electron-directing groups on the ligand scaffold.

Selective photocatalytic oxidation of aromatic alcohols using B-g-C3N4/Bi2WO6 composites

In this work, B-g-C3N4/Bi2WO6 composites were synthesized by simple hydrothermal reaction and calcination, and their morphology, composition and physicochemical properties were characterized. The results show that the composite can selectively oxidize aromatic alcohols to aromatic aldehydes under visible light. The conversion rate of benzyl alcohol can reach 98.9% and the selectivity can reach 99% in 4 h, which are 1.59 times and 5.03 times that of Bi2WO6 alone, respectively. Further photoelectric performance investigation revealed that the recombination of B-g-C3N4 with Bi2WO6 effectively enhanced the separation of photogenerated carriers of B-g-C3N4 and suppressed the generation of holes on Bi2WO6, thereby improving the photocatalytic activity and the selectivity of the catalytic reaction of p-benzyl alcohol. In addition, the electronic effect and steric hindrance effect of substituents on the benzene ring on the selective catalytic oxidation of aromatic alcohols were also explored. Our work also reveals that the bandgap structure of the composites and the efficient separation of photogenerated electron transport are key factors to improve the photocatalytic reactivity and selectivity of organic reactions.

Mo(VI)-catalyzed conversion of nitriles to amides with hydrogen peroxide in ethanol

A method for the preparation of primary amides from nitriles using hydrogen peroxide and a catalytic amount of sodium molybdate in ethanol is described. Using this method, nitriles including aromatic nitriles, aromatic heterocyclic nitriles and aliphatic nitriles were converted into the corresponding amides in moderate to high yields. Electronic and steric effects of substituent have a significant effect on the reactivity of nitrile, nitriles with electron-withdrawing group at the para or meta position show high reactivities and they can be converted into the corresponding amide in good to high yield at room temperature.

Electronic and Steric Effects on the Reactivity of Seleniranium Ions with Alkenes in the Gas Phase.

Gas phase ion-molecule reactions between seleniranium ions, R-c-SeCH2CH2+, and cis-cyclooctene were used to probe electronic and steric effects of substituents on kinetics and branching ratios. The second-order rate coefficients increased in the order p-OMeC6H4 < C6H5 < p-BrC6H4 < p-CF3C6H4 < m-NO2C6H4, giving a Hammett plot with R2 = 0.98 and ρ = +1.66. The two main pathways include direct transfer of the selenium moiety to the incoming alkene (π-ligand exchange) and the less favored ring-opening by attack at an iranium carbon to give a cis-bicyclic selenonium ion as supported by density functional theory (DFT) calculations. Branching ratios of each pathway indicated that electron-withdrawing groups directed more attack at carbon than selenium in agreement with previous solution-phase results. Increased steric bulk on selenium was investigated by changing the R group from a methyl to t-butyl, which not only shut down π-ligand exchange but also significantly reduced the overall reactivity. Finally, the reactivity of the iranium ion derived from Se-methylselenocysteine was investigated and shown to react faster and favor π-ligand exchange as the leaving group was changed from ethene to acrylic acid.

Vanadium complexes bearing 8-anilide-5,6,7-trihydroquinoline ligands for ethylene (co-)polymerization.

Several trivalent and pentavalent vanadium complexes bearing 8-anilide-5,6,7-trihydroquinoline ligands were synthesized. These vanadium complexes were identified by elemental analysis, FTIR spectroscopy and NMR. Single crystals of trivalent vanadium complexes V2, V3', and V4 and pentavalent vanadium complexes V5 and V7 were further obtained and identified by X-ray single crystal diffraction. In addition, the catalytic performance of these catalysts was adjusted by controlling the electronic and steric effects of substituents in the ligands. In the presence of diethylaluminium chloride, complexes V5-V7 displayed high activity (up to 82.8 × 106 g molV-1 h-1) and good thermal stability toward ethylene polymerization. In addition, the copolymerization ability of complexes V5-V7 was evaluated, and complexes V5-V7 displayed high activity (up to 105.6 × 106 g molV-1 h-1) and high copolymerization ability toward ethylene/norbornene copolymerization. By adjusting the polymerization conditions, copolymers with norbornene insertion ratios of 8.1%-30.9% can be obtained. Complex V7 was further studied for ethylene/1-hexene copolymerization, and the obtained copolymer displayed a moderate 1-hexene insertion ratio of 1.2%. Complex V7 displayed high activity and high copolymerization ability while having thermal stability. The results showed that 8-anilide-5,6,7-trihydroquinoline ligands with fused rigid-flexible rings were beneficial for vanadium catalysts.

Iron(ii) carboxylates and simple carboxamides: an inexpensive and modular catalyst system for the synthesis of PLLA and PLLA-PCL block copolymers.

The combination of inexpensive Fe(ii) acetate with low molecular weight aliphatic carboxamides in situ generates an effective catalyst system for the ring opening polymerisation of lactones. PLLAs were produced in melt conditions with molar masses of up to 15 kg mol-1, narrow dispersity (Đ = 1.03), and without racemisation. The catalytic system was investigated in detail with regard to Fe(ii) source, and steric and electronic effects of the amide's substituents. Furthermore, the synthesis of PLLA-PCL block copolymers of very low randomness was achieved. This commercially available, inexpensive, modular, and user-friendly catalyst mixture may be suitable for polymers with biomedical applications.

Tuning catalytic activity with steric and electron-withdrawing effects of a porphyrin substituent

The reactivity, spectroscopic, and kinetic studies of the catalytic reactions showed that the catalytic activity is determined by the balance of the rates of the formation, reaction, and decomposition reactions of the reactive intermediate.

Iridium-catalyzed regioselective B(3,6)-dialkenylation or B(4)-alkenylation of o-carboranes via B-H activation and 1,2-carbon migration of alkynes.

An efficient Ir-catalyzed cage boron alkenylation of 1-(2'-picolyl)-o-carboranes with diarylacetylenes has been developed, leading to a wide variety of B-H geminal addition products via 1,2-carbon migration of alkynes. The steric effect of cage carbon substituents has a great impact on the regioselectivity of such alkenylation reactions.

Iridium‐Catalysed C−H Borylation of Fluoroarenes: Insights into the Balance between Steric and Electronic Control of Regioselectivity

AbstractThe iridium catalysed C−H borylation of polyfluorinated arenes and heteroarenes occurs rapidly and efficiently. As with other borylation reactions, whilst steric parameters dominate, an underlying electronic influence on reaction selectivity can be observed. Notably borylation regioselectivity in fluorinated (hetero)arenes is determined by purely electronic effects except for ortho‐borylation between two fluorine atoms where steric effects of fluorine substituents become apparent. Borylation at the para position with respect to fluorine is disfavoured whereas a strong electronic preference for borylation para to the azinyl nitrogen of pyridine is observed. When these features co‐operate high selectivity can be expected. For these reactions, computations based on transition state, rather than intermediate, energies in iridium geometries showed excellent agreement between predicted and observed selectivities.