Reactivities Of Substrates Research Articles

Directional Construction of the Highly Stable Active-Site Ensembles at Sub-2nm to Enhance Catalytic Activity and Selectivity.

Precise control over the size, species, and breakthrough of the activity-selectivity trade-off are great challenges for sub-nano non-noble metal catalysts. Here, for the first time, a "multiheteroatom induced SMSI + in situ P activation" strategy that enables high stability and effective construction of sub-2nm metal sites for optimizing selective hydrogenation performance is developed. It is synthesized the smallest metal phosphide clusters (<2 nm) including from unary to ternary non-noble metal systems, accompanied by unprecedented thermal stability. In the proof-of-concept demonstration, further modulation of size and species results in the creation of a sub-2nm site platform, directionally achieving single atom (Ni1), Ni1+metal cluster (Ni1+Nin), or novel Ni1+metal phosphide cluster synergistic sites (Ni1+Ni2Pn), respectively. Based on thorough structure and mechanism investigation, it is found the Ni1+Ni2Pn site is motivated to achieve electronic structure self-optimizing through synergistic SMSI and site coupling effect. Therefore, it speeds up the substrate adsorption-desorption kinetics in semihydrogenation of alkyne and achieves superior catalytic activity that is 56 times higher than the Ni1 site under mild conditions. Compared to traditional active sites, this may represent the highly effective integration of atom utilization, thermal stability, and favorable site requirements for chemisorption properties and reactivities of substrates.

Synergistic Visible Light Photocatalysis with Organocatalysis.

In recent years, the strategy of merging visible light photocatalysis and organocatalysis has been utilized and applied in a wide range of reactions. Taking advantage of synergistic visible light photocatalysis with organocatalysis, remarkable progress has recently been achieved in modern chemical synthesis. In these dual catalytic systems, photocatalysts or photosensitizers absorb visible light to induce their photo-excited states which can activate unreactive substrates via electron or energy transfer mechanisms, and organocatalysts are usually employed to control the chemical reactivities of the other substrates. This review mainly focuses on the recent development of cooperative catalysis by the combination of organocatalysis and photocatalysis in recent organic synthesis.

Cesium-Fluoride-Promoted Synthesis of Stable Organocesium Reagents and Their Ambident Reactivities with Arynes.

Described are the diverse reactivities of novel, stable, ambident thio-organocesium reagents (bearing electron withdrawing groups) against benzynes. Reactions at reflux temperature predominantly led to the generation of various functionalized stable sulfonium ylides and at 40 °C the same reaction underwent direct c-arylation. Furthermore, lack of internal hydrogen on the cesium reagent helped to produce different ortho-bifunctional arynes in both the reactions. Interestingly, depending on the reactivities of substrates, the one-pot tri-component procedure generated either ylides or σ-bond insertion products.

Catalytic Enantioselective Construction of 6‐4 Ring‐Junction All‐Carbon Stereocenters and Mechanistic Insights

Comprehensive SummaryDeveloping reactions for the synthesis of 6‐6‐4 and 6‐4 carbocyclic scaffolds with a chiral quaternary center at the bridgehead position is highly desired, considering the existence of such skeletons in natural products with biological activities and the potential of using these molecules for downstream studies in chemical biology and medicinal chemistry. Report here is accessing these target skeletons with high chemo‐, regio‐ and enantio‐selectivities through Pd(II)/chiral N,N’‐disulfonyl bisimidazoline (Bim) ligand‐catalyzed asymmetric reaction of yne‐allenones and arylboronic acids. Realization of 6‐6‐4 skeleton with a ring‐junction all‐carbon stereocenter is a one‐step process while synthesizing 6‐4 skeleton is a two‐step process, which begins with intramolecular [2 + 2] reaction of allenes with alkynes, followed by Pd‐catalyzed asymmetric addition of arylboronic acids to cyclic enones generated in the first step. Noteworthy is that chiral Bim ligand as a C2‐symmetric N,N’‐bidentateanionic ligand, designed by us, in coordinating with Pd catalyst was first applied to catalyze asymmetric 1,4‐conjugate addition reaction with the high catalytic performance (the reaction can be carried out in air). DFT calculations have been applied to understand how these reactions take place, the origins of enantioselectivity, and relative reactivities of different substrates.

An Adaptive Auto‐Synthesizer using Online PAT Feedback to Flexibly Perform a Multistep Reaction

AbstractAutomated chemical synthesizers have become more common in recent years but struggle to apply rigid procedures to broad substrate scopes. We have developed an adaptive auto‐synthesizer that uses online HPLC and FTIR measurements to adapt to the changing reactivities of different substrates, allowing precise control of reaction conditions. To do so, we designed a flexibly‐timed procedure consisting of specific actions performed by our platform when specific reaction‐monitoring checkpoints are met. Online HPLC allowed our system to autonomously separate, label and quantify most reaction components, with orthogonal FTIR enabling non‐UV active species to be additionally tracked. We tested our platform with CDI‐mediated multistep amidation reactions using a variety of different acid and amine substrates. To demonstrate the high reproducibility and control afforded by our system, we determined the relative rates of both acid activation and subsequent amidation, providing insight into substrate reactivities and the reaction mechanism.

PdII-Catalyzed Site-selective β- and γ-C(sp3)-H Arylation of Primary Aldehydes Controlled by Transient Directing Groups.

Pd(II)-catalyzed site-selective β- and γ-C(sp3)-H arylation of primary aldehydes is developed by rational design of L,X-type transient directing groups (TDG). External 2-pyridone ligands are identified to be crucial for the observed reactivity. By minimizing the loading of acid additives, the ligand effect is enhanced to achieve high reactivities of the challenging primary aldehyde substrates. Site selectivity can be switched from the proximate to the relatively remote position by changing the bite angle of TDG to match the desired palladacycle size. Experimental and computational investigations support this rationale for designing TDG to potentially achieve remote site-selective C(sp3)-H functionalizations.

Computational exploration of copper catalyzed vinylogous aerobic oxidation of unsaturated compounds

Selective oxidation is one of the most important and challenging transformations in both academic research and chemical industry. Recently, a highly selective and efficient way to synthesize biologically active γ-hydroxy-α,β-unsaturated molecules from Cu-catalyzed vinylogous aerobic oxidation of α,β- and β,γ-unsaturated compounds has been developed. However, the detailed reaction mechanism remains elusive. Herein, we report a density functional theory study on this Cu-catalyzed vinylogous aerobic oxidation of γ,γ-disubstituted α,β- and β,γ-unsaturated isomers. Our computational study unveils detailed mechanism for each elementary step, i.e. deprotonation, O2 activation, and reduction. Besides, the origin of regioselectivity, divergent reactivities of substrates as well as reducing agents, and the byproduct generation have also been investigated. Notably, the copper catalyst retains the + 2 oxidation state through the whole catalytic cycle and plays essential roles in multiple steps. These findings would provide hints on mechanistic studies and future development of transition metal-catalyzed aerobic oxidation reactions.

Mechanism, reactivity, and selectivity of the iridium-catalyzed C(sp3)-H borylation of chlorosilanes.

The iridium-catalyzed C(sp3)-H borylation of methylchlorosilanes is investigated by means of density functional theory, using the B3LYP and M06 functionals. The calculations establish that the resting state of the catalyst is a seven-coordinate Ir(v) species that has to be converted into an Ir(iii)tris(boryl) complex in order to effect the oxidative addition of the C-H bond. This is then followed by a C-B reductive elimination to yield the borylated product, and the catalytic cycle is finally completed by the regeneration of the active catalyst over two facile steps. The two employed functionals give somewhat different conclusions concerning the nature of the rate-determining step, and whether reductive elimination occurs directly or after a prior isomerization of the Ir(v) hydride intermediate complex. The calculations reproduce quite well the experimentally-observed trends in the reactivities of substrates with different substituents. It is demonstrated that the reactivity can be correlated to the Ir-C bond dissociation energies of the corresponding Ir(v) hydride intermediates. The effect of the chlorosilyl group is identified to originate from the α-carbanion-stabilizing effect of the silicon, which is further reinforced by the presence of an electron-withdrawing chlorine substituent. Furthermore, the source of selectivity for the borylation of primary over secondary C(sp3)-H can be explained on a steric basis, by repulsion between the alkyl group and the Ir/ligand moiety. Finally, the difference in the reactivity between C(sp3)-H and C(sp2)-H borylation is investigated and rationalized in terms of distortion/interaction analysis.

Relative reactivities of bromine-substituted substrates toward bromophilic attack by a carbanion

Relative reactivities of bromine-substituted substrates toward bromophilic attack by a carbanion

Highly Efficient and Reusable Copper-Catalyzed N-Arylation of Nitrogen-Containing Heterocycles with Aryl Halides

CuO/AB was found to be a simple and efficient catalyst for the N-arylation of a variety of nitrogen-containing heterocycles, giving the products in excellent yields.

Radiolysis Studies on the Destruction of Microcystin-LR in Aqueous Solution by Hydroxyl Radicals

In this study, steady-state and time-resolved radiolysis methods were used to determine the primary reaction pathways and kinetic parameters for the reactions of hydroxyl radical with microcystin-LR (MC-LR). The fundamental kinetic data is critical for the accurate evaluation of hydroxyl-radical based technologies for the destruction of this problematic class of cyanotoxins. The bimolecular rate constant for the reaction of hydroxyl radical with MC-LR is 2.3 (+/-0.1) x 10(10) M(-1)s(-1) based on time-resolved competition kinetics with SCN-at low conversions using pulsed radiolysis experiments. The reaction of hydroxyl radical with MC-LR can occur via a number of competing reaction pathways, including addition to the benzene ring and diene and abstraction of aliphatic hydrogen atoms. LC-MS analyses indicate the major products from the reaction of hydroxyl radicals with MC-LR involve addition of hydroxyl radical to the benzene ring and diene moieties of the Adda side chain. Transient absorption spectroscopy monitored between 260-500 nm, following pulsed hydroxyl radical generation, indicate the formation of a transient species with absorption maxima at 270 and 310 nm. The absorption maxima and lifetime of the transient species are characteristic of hydroxycyclohexadienyl radicals resulting from the addition of hydroxyl radical to the benzene ring. The rate constant for the formation of hydroxycyclohexadienyl radical is 1.0 (+/-0.1) x 10(10) M(-1)s(-1) accounting for approximately 40% of the primary reaction pathways. Representative rate constants and partitioning of hydroxyl radical reactions were assessed based on the reactivities of surrogate substrates and individual amino acids. Summation of the individual reactivities of hydroxyl radical at the different reactive sites (amino acids) leads to a rate constant of 2.1 x 10(10) M(-1) s(-1) in good agreementwith the rate constant determined in our studies. The relative magnitude of the rate constants for the reactions of hydroxyl radical with the individual amino acids and appropriate surrogates, suggest 60-70% reactions of hydroxyl radical occur at the benzene and diene functional groups of the Adda moiety.

Computational Study of Reactivity and Transition Structures in Nucleophilic Substitutions on Benzyl Bromides

AbstractDFT computations on the mechanisms of nucleophilic substitutions on benzyl bromides were performed and the calculated activation parameters were compared with experimentally acquired data. In vacuo, the presence of electron‐withdrawing (e‐w) groups on the benzyl bromides accelerated the reactions and the calculated ΔG‡/ΔH‡/ΔS‡ vs. σ plots were linear, while in solvents there were breaks in the calculated and measured ΔG‡/ΔH‡ vs. σ+ plots of the reactions between the benzyl bromides and Br–, both with electron‐donating (e‐d) and with e‐w substituents accelerating the reactions. The calculated ΔS‡ values appeared to be independent of the substituents. In solvents, the calculated ΔG‡/ΔH‡/ΔS‡ vs. σ+ plots for the reactions between benzyl bromides and pyridine were linear, whereas breaks were observed in the plots of the measured data. These reactions were promoted by e‐d substituents, but the measured reactivities of substrates bearing e‐w groups were higher than expected. No breaks in the ΔG‡/ΔH‡/ΔS‡ vs. σ plots were observed when the substituents on the pyridine nucleophile were changed. The best agreement between the calculated and measured values was obtained for the least solvent‐dependent ΔG‡ parameter. The experimentally measured ΔS‡ and ΔH‡ data were influenced by the rearrangement of the solvent molecules. The calculated structural parameters of the transition states (TSs) varied linearly with the substituent constants, with loose and tight distorted trigonal‐bipyramidal TSs being formed by benzyl bromides bearing e‐d and e‐w groups, respectively. The reactions proceeded by SN2 mechanisms; only the transition structures were changed with the substituents and the media. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)

Quantitative Structure−Activity Relationship Based Quantification of the Impacts of Enzyme−Substrate Binding on Rates of Peroxidase-Mediated Reactions of Estrogenic Phenolic Chemicals

The initial rates of horseradish peroxidase (HRP)-mediated enzymatic reactions of 15 assorted aqueous phase phenolic chemicals were studied. The associated reaction rate constants were found to correlate quantitatively with two independent variables: the highest-occupied molecular orbital energy (E(HOMO)) defining the intrinsic redox reactivities of the phenolic substrates and the distance between a substrate and the deltaN of HIS42's imidazole ring in an HRP/substrate binding complex, obtained through molecular simulations. Highly correlated quantitative structure-activity relationship (QSAR) equations were thus developed. This work provides insights into the impacts that HRP/substrate binding may have on HRP-mediated reactions. Additionally, the QSAR equations developed in the work may serve as a basis to further explore the potential use of HRP-mediated reactions in the treatment of estrogenic contaminants, and they constitute an important tool for redesign and screening of potential proteomic modifications to the wild-type HRP structure intended to enhance reactivity toward selected substrates.

Synthesis of Cyclic Peroxides by Chemo- and Regioselective Peroxidation of Dienes with Co(II)/O2/Et3SiH

In the competitive peroxidation of mixtures of two alkenes with Co(II)/O(2)/Et(3)SiH, it was found that the relative reactivities of the alkene substrates are influenced by three major factors:. (1) relative stability of the intermediate carbon-centered radical formed by the reaction of the alkene with HCo(III) complex, (2) steric effects around the C=C double bond, and (3) electronic factors associated with the C=C double bond. Consistent with results from simple alkenes, the chemo- and regioselective peroxidation of dienes was also realized. Depending on the diene structure, the product included not only the expected acyclic unsaturated triethylsilyl peroxides but also 1,2-dioxolane and 1,2-dioxane derivatives via intramolecular cyclization of the unsaturated peroxy radical intermediates.

Aminophosphonate inhibitors of dialkylglycine decarboxylase: structural basis for slow binding inhibition.

The kinetics of inhibition of dialkylglycine decarboxylase by five aminophosphonate inhibitors are presented. Two of these [(R)-1-amino-1-methylpropanephosphonate and (S)-1-aminoethanephosphonate] are slow binding inhibitors. The inhibitors follow a mechanism in which a weak complex is rapidly formed, followed by slow isomerization to the tight complex. Here, the tight complexes are bound 10-fold more tightly than the weak, initial complexes. The slow onset inhibition occurs with t(1/2) values of 1.3 and 0.55 min at saturating inhibitor concentrations for the AMPP and S-AEP inhibitors, respectively, while dissociation of these inhibitor complexes occurs with t(1/2) values of 13 and 4.6 min, respectively. The X-ray structures of four of the inhibitors in complex with dialkylglycine decarboxylase have been determined to resolutions ranging from 2.6 to 2.0 A, and refined to R-factors of 14.5-19.5%. These structures show variation in the active site structure with inhibitor side chain size and slow binding character. It is proposed that the slow binding behavior originates in an isomerization from an initial complex in which the PLP pyridine nitrogen-D243 OD2 distance is approximately 2.9 A to one in which it is approximately 2.7 A. The angles that the C-P bonds make with the p orbitals of the aldimine pi system are correlated with the reactivities of the analogous amino acid substrates, suggesting a role for stereoelectronic effects in Schiff base reactivity.

Relative reactivities of halogen-substituted substrates (R-Br, R-Cl) toward the halophilic attack by a carbanion

Relative reactivities of bromine-substituted substrates (R-Br) or chlorine-substituted subsrates (R-Cl) toward bromophilic or chlorophilic attack by a carbanion have been evaluated by the intermolecular competition kinetics. Relative reactivity orders are CF^3CFBr^2＞CF^3CBr^3 CBr^4＞CHBr^3＞CF^3CFBrCF^2Br＞CF^2Br^2＞BrCF^2CF^2Br＞BrCH^2CO^2Et≥BrCF^2CFHBr＞CH^2Br^2＞BrCH^2CH^2Br, and Cl^3CNO^2＞Cl^3CCN＞CL^3CCOPh＞cyclo-C^5Cl^6＞Cl^3CCOCl＞CCl^3CF^2Cl＞CCl^3CF^3≥CCl^4＞CCl^3CCl^3≥CCl^3(CF^2)Cl＞Cl^3CCOCCl^3CCl^3(CF^2)Cl＞ClCCO^2Et＞Cl^3CF＞Cl^3CPh＞Cl^3CCH^2O^2CCH^3

Longitudinal distribution of ozone and chlorine in the human respiratory tract: simulation of nasal and oral breathing with the single-path diffusion model.

In the single-path model of the respiratory system, gas transport occurs within a conduit of progressively increasing cross-sectional and surface areas by a combination of flow, longitudinal dispersion, and lateral absorption. The purpose of this study was to use bolus inhalation data previously obtained for chlorine (Cl(2)) and for ozone (O(3)) to test the predictive capability of the single-path model and to adjust input parameters for applying the model to other exposure conditions. The data, consisting of uptake fraction as a function of bolus penetration volume, were recorded on 10 healthy nonsmokers breathing orally as well as nasally at alternative air flows of 150, 250, and 1000 ml/s. By employing published data for airway anatomy, gas-phase dispersion coefficients, and gas-phase mass transfer coefficients while neglecting diffusion limitations in the mucus phase, the single-path model was capable of predicting the uptake distribution for O(3) but not the steeper distribution that was observed for Cl(2). To simultaneously explain the data for these two gases, it was necessary to increase gas-phase mass transfer coefficients and to include a finite diffusion resistance of O(3) within the mucous layer. The O(3) reaction rate constants that accounted for this diffusion resistance, 2 x 10(6) s(-1) in the mouth and 8 x 10(6) s(-1) in the nose and lower airways, were much greater than previously reported reactivities of individual substrates found in mucus.

Relative reactivities of halogen-substituted substrates (R-Br, R-Cl) toward the halophilic attack by a carbanion

Relative reactivities of bromine-substituted substrates (R-Br) or chlorine-substituted substrates (R-Cl) toward bromophilic or chlorophilic attack by a carbanion have been evaluated by the intermolecular competition kinetics. Relative reactivity orders are CF 3 CFBr 2 ＞CF 3 CBr 3 ≥CBr 4 ＞CHBr 3 ＞CF 3 CFBrCF 2 Br＞CF 2 Br 2 ＞ BrCF 2 CF 2 Br＞BrCH 2 CO 2 Et≥BrCF 2 CFHBr＞CH 2 Br 2 ＞BrCH 2 CH 2 Br, and Cl 3 CNO 2 ＞ Cl 3 CCN＞Cl 3 CCOPh ＞cyclo-C 5 Cl 6 ＞Cl 3 CCOCl＞CCl 3 CF2Cl＞CCl 3 CF 3 ≥CCl 4 ＞ CCl 3 CCl 3 ≥CCl 3 (CF 2 ) 2 Cl＞Cl 3 CCOCCl 3 ＞CCl 3 (CF 2 ) 6 Cl＞Cl 3 CCO 2 Et＞Cl 3 CF ＞Cl 3 CPh＞Cl 3 CCH 2 O 2 CCH 3 .

Asymmetric synthesis of chiral amines with ?-transaminase

The asymmetric synthesis of chiral amines using prochiral ketones was carried out with (S)-specific omega-transaminase (omega-TA) from Vibrio fluvialis JS17. This reaction is inhibited severely by both products, (S)-amine and deaminated ketone. In addition, thermodynamic equilibrium strongly favored the reverse reaction. L-Alanine proved to be the best amino donor based on easy removal of the products. Optimal pH of the reactions with both whole cells and cell-free extract was 7. Amino acceptor reactivities of ketone substrates and reaction profiles of the asymmetric synthesis showed that the initial rate as well as the reaction yield were lower when the resulting (S)-amine from a prochiral ketone substrate was a more reactive amino donor. The yield could be increased dramatically by removing pyruvate, which is a more inhibitory product than (S)-alpha-methylbenzylamine [(S)-alpha-MBA] when acetophenone and L-alanine are used as an amino acceptor and donor, respectively. The removal of pyruvate was carried out by incorporating lactate dehydrogenase (LDH) in cell-free extract or by using whole cells. The whole cell reaction yielded a much better result. When 25 mM benzylacetone and 30 mM acetophenone were used as an amino acceptor with 300 mM L-alanine, 90.2% and 92.1% of the reaction yields after 1 day were obtained with whole cells, respectively. Enantiomeric excesses of both (S)-alpha-MBA and (S)-1-methyl-3-phenylpropylamine [(S)-MPPA] were all above 99%.

Quantitative Sorption Experiments on Ti-Zeolites and Relation with α-Olefin Oxidation by H2O2

A tracer chromatographic method is used to study liquid-phase adsorption on TS-1, Ti-β, and Ti-MCM-41. Partition coefficients for alkenes, alkanes, epoxides, and other polar products are strongly dependent on the carrier solvent. Linear α-olefins are concentrated inside the TS-1 micropores, particularly when methanol is the solvent. This agrees well with the superior initial rates of olefin epoxidation with TS-1 in methanol. Sorption also governs the relative reactivities of olefin substrates, especially in competitive experiments. Thus, under truly initial conditions, 1-hexene is less reactive than 1-octene or 1-nonene. For the latter substrates, however, deactivation is fast, especially in methanol. This process is related to the strong adsorption of higher 1,2-epoxyalkanes in TS-1 in methanol. Deactivation due to competitive epoxide adsorption is slower in acetone, making this a more suitable solvent than methanol for 1-nonene epoxidation with TS-1. Overall, physisorption effects play a dominant role in the small pore TS-1 catalyst, due to the close interaction of substrates such as alkenes with the pore wall. Wider-pore catalysts such as Ti-β and especially Ti-MCM-41 do not adsorb olefins as selectively and hence intraporous olefin concentrations are much lower.