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Stephen L Buchwald - One of the best experts on this subject based on the ideXlab platform.
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a neophyl palladacycle as an air and thermally stable precursor to Oxidative Addition complexes
Organic Letters, 2021Co-Authors: Ryan P King, Shane W Krska, Stephen L BuchwaldAbstract:The utilization of isolated Palladium Oxidative Addition Complexes (OACs) has had a significant impact on Pd-catalyzed and Pd-mediated cross-coupling reactions. Despite their importance, widespread utility of OACs has been limited by the instability of their precursor complexes. Herein, we report the use of Campora's palladacycle as a new, more stable precursor to Pd OACs. Using this palladacycle, a series of biarylphosphine ligated OACs, including those with pharmaceutical-derived aryl halides and relevance to bioconjugation, were prepared.
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a ligand exchange process for the diversification of palladium Oxidative Addition complexes
Organic Letters, 2021Co-Authors: Ryan P King, Shane W Krska, Stephen L BuchwaldAbstract:Palladium Oxidative Addition complexes (OACs) have recently emerged as useful tools to enable challenging bond connections. However, each OAC can only be formed with one dative ligand at a time. As no one ligand is optimal for every cross-coupling reaction, we herein disclose a ligand exchange protocol for the preparation of a series of OACs bearing a variety of ancillary ligands from one common complex. These complexes were further applied to cross-coupling transformations.
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palladium protein Oxidative Addition complexes by amine selective acylation
Journal of the American Chemical Society, 2020Co-Authors: Heemal H Dhanjee, Ivan Buslov, Bradley L Pentelute, I W Windsor, Ronald T Raines, Stephen L BuchwaldAbstract:Palladium Oxidative Addition complexes (OACs) are traditionally accessed by treating an aryl halide-containing substrate with a palladium(0) source. Here, a new strategy to selectively prepare stable OACs from amino groups on native proteins is presented. The approach relies on an amine-selective acylation reaction that occurs without modification of a preformed palladium(II)-aryl group. Once transferred onto a protein substrate, the palladium(II)-aryl group facilitates conjugation by undergoing reaction with a second, cysteine-containing protein. This operationally simple method is applicable to native, nonengineered enzymes as well as antibodies and is carried out in an aqueous setting and open to air. The resulting Pd-protein OACs are stable, storable reagents that retain biological activity and can be used to achieve protein-protein cross-coupling at nanomolar concentrations within hours.
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protein protein cross coupling via palladium protein Oxidative Addition complexes from cysteine residues
Journal of the American Chemical Society, 2020Co-Authors: Heemal H Dhanjee, Azin Saebi, Ivan Buslov, Alexander R Loftis, Stephen L Buchwald, Bradley L PenteluteAbstract:Few chemical methods exist for the covalent conjugation of two proteins. We report the preparation of site-specific protein-protein conjugates that arise from the sequential cross-coupling of cysteine residues on two different proteins. The method involves the synthesis of stable palladium-protein Oxidative Addition complexes (Pd-protein OACs), a process that converts nucleophilic cysteine residues into an electrophilic S-aryl-Pd-X unit by taking advantage of an intramolecular Oxidative Addition strategy. This process is demonstrated on proteins up to 83 kDa in size and can be conveniently carried out in water and open to air. The resulting Pd-protein OACs can cross-couple with other thiol-containing proteins to arrive at homogeneous protein-protein bioconjugates.
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pharmaceutical diversification via palladium Oxidative Addition complexes
Science, 2019Co-Authors: Ryan P King, Mycah R Uehling, Shane W Krska, Tim Cernak, Stephen L BuchwaldAbstract:Palladium-catalyzed cross-coupling reactions have transformed the exploration of chemical space in the search for materials, medicines, chemical probes, and other functional molecules. However, cross-coupling of densely functionalized substrates remains a major challenge. We devised an alternative approach using stoichiometric quantities of palladium Oxidative Addition complexes (OACs) derived from drugs or drug-like aryl halides as substrates. In most cases, cross-coupling reactions using OACs proceed under milder conditions and with higher success than the analogous catalytic reactions. OACs exhibit remarkable stability, maintaining their reactivity after months of benchtop storage under ambient conditions. We demonstrated the utility of OACs in a variety of experiments including automated nanomole-scale couplings between an OAC derived from rivaroxaban and hundreds of diverse nucleophiles, as well as the late-stage derivatization of the natural product k252a.
Alan F Heyduk - One of the best experts on this subject based on the ideXlab platform.
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group iv imino semiquinone complexes obtained by Oxidative Addition of halogens
Inorganic Chemistry, 2008Co-Authors: Karen J Blackmore, Mason R Haneline, Joseph W Ziller, Alan F HeydukAbstract:An isostructural series of titanium, zirconium, and hafnium complexes, M[ap]2L2 (M = Ti, Zr, Hf; L = THF, pyridine), of the redox-active 4,6-di-tert-butyl-2-tert-butylamidophenolate ligand ([ap]2−) have been prepared. The zirconium and hafnium derivatives react readily with halogen oxidants such as XeF2, PhICl2, and Br2, leading to products in which one-electron oxidation of each [ap]2− ligand accompanies halide Addition to the metal center. Iodine proved to be too weak of an oxidant to yield the corresponding Oxidative Addition product, and under no conditions could halogen Oxidative Addition products be obtained for titanium. According to X-ray crystallographic studies, the zirconium and hafnium oxidation products are best formulated as MX2[isq·]2 ([isq·]− = 4,6-di-tert-butyl-2-tert-butylimino-semiquinonate; M = Zr, Hf; X = F, Cl, Br) species, in which the molecule is symmetric with each redox-active ligand in the semiquinone oxidation state. Temperature-dependent magnetization measurements suggest a si...
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group iv imino semiquinone complexes obtained by Oxidative Addition of halogens
Inorganic Chemistry, 2008Co-Authors: Karen J Blackmore, Mason R Haneline, Joseph W Ziller, Michael B Sly, Alan F HeydukAbstract:An isostructural series of titanium, zirconium, and hafnium complexes, M[ap] 2L 2 (M = Ti, Zr, Hf; L = THF, pyridine), of the redox-active 4,6-di- tert-butyl-2- tert-butylamidophenolate ligand ([ap] (2-)) have been prepared. The zirconium and hafnium derivatives react readily with halogen oxidants such as XeF 2, PhICl 2, and Br 2, leading to products in which one-electron oxidation of each [ap] (2-) ligand accompanies halide Addition to the metal center. Iodine proved to be too weak of an oxidant to yield the corresponding Oxidative Addition product, and under no conditions could halogen Oxidative Addition products be obtained for titanium. According to X-ray crystallographic studies, the zirconium and hafnium oxidation products are best formulated as MX 2[isq.] 2 ([isq.] (-) = 4,6-di- tert-butyl-2- tert-butylimino-semiquinonate; M = Zr, Hf; X = F, Cl, Br) species, in which the molecule is symmetric with each redox-active ligand in the semiquinone oxidation state. Temperature-dependent magnetization measurements suggest a singlet ( S = 0) ground-state for the diradical complexes with a thermally accessible triplet ( S = 1) excited state. Solution electron paramagnetic resonance (EPR) spectra are consistent with this assignment, showing both Delta m s = 1 and Delta m s = 2 transitions for the antiferromagnetically coupled electrons.
Bradley L Pentelute - One of the best experts on this subject based on the ideXlab platform.
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palladium protein Oxidative Addition complexes by amine selective acylation
Journal of the American Chemical Society, 2020Co-Authors: Heemal H Dhanjee, Ivan Buslov, Bradley L Pentelute, I W Windsor, Ronald T Raines, Stephen L BuchwaldAbstract:Palladium Oxidative Addition complexes (OACs) are traditionally accessed by treating an aryl halide-containing substrate with a palladium(0) source. Here, a new strategy to selectively prepare stable OACs from amino groups on native proteins is presented. The approach relies on an amine-selective acylation reaction that occurs without modification of a preformed palladium(II)-aryl group. Once transferred onto a protein substrate, the palladium(II)-aryl group facilitates conjugation by undergoing reaction with a second, cysteine-containing protein. This operationally simple method is applicable to native, nonengineered enzymes as well as antibodies and is carried out in an aqueous setting and open to air. The resulting Pd-protein OACs are stable, storable reagents that retain biological activity and can be used to achieve protein-protein cross-coupling at nanomolar concentrations within hours.
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protein protein cross coupling via palladium protein Oxidative Addition complexes from cysteine residues
Journal of the American Chemical Society, 2020Co-Authors: Heemal H Dhanjee, Azin Saebi, Ivan Buslov, Alexander R Loftis, Stephen L Buchwald, Bradley L PenteluteAbstract:Few chemical methods exist for the covalent conjugation of two proteins. We report the preparation of site-specific protein-protein conjugates that arise from the sequential cross-coupling of cysteine residues on two different proteins. The method involves the synthesis of stable palladium-protein Oxidative Addition complexes (Pd-protein OACs), a process that converts nucleophilic cysteine residues into an electrophilic S-aryl-Pd-X unit by taking advantage of an intramolecular Oxidative Addition strategy. This process is demonstrated on proteins up to 83 kDa in size and can be conveniently carried out in water and open to air. The resulting Pd-protein OACs can cross-couple with other thiol-containing proteins to arrive at homogeneous protein-protein bioconjugates.
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palladium Oxidative Addition complexes for peptide and protein cross linking
Journal of the American Chemical Society, 2018Co-Authors: Koji Kubota, Bradley L Pentelute, Peng Dai, Stephen L BuchwaldAbstract:A new method for cysteine–lysine cross-linking in peptides and proteins using palladium Oxidative Addition complexes is presented. First, a biarylphosphine-supported palladium reagent is used to transfer an aryl group bearing an O-phenyl carbamate substituent to a cysteine residue. Next, this carbamate undergoes chemoselective acyl substitution by a proximal lysine to form a cross-link. The linkage so formed is stable toward acid, base, oxygen, and external thiol nucleophiles. This method was applied to cross-link cysteine with nearby lysines in sortase A*. Furthermore, we used this method for the intermolecular cross-linking between a peptide and a protein based on the p53-MDM2 interaction. These studies demonstrate the potential for palladium-mediated methods to serve as a platform for the development of future cross-linking techniques for peptides and proteins with natural amino acid residues.
Matthew S Sigman - One of the best experts on this subject based on the ideXlab platform.
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pd quinox catalyzed allylic relay suzuki reactions of secondary homostyrenyl tosylates via alkene assisted Oxidative Addition
ChemInform, 2014Co-Authors: Benjamin J Stokes, Amanda J Bischoff, Matthew S SigmanAbstract:Mechanistic studies suggest that the Oxidative Addition requires direct alkene involvement.
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pd quinox catalyzed allylic relay suzuki reactions of secondary homostyrenyl tosylates via alkene assisted Oxidative Addition
Chemical Science, 2014Co-Authors: Benjamin J Stokes, Amanda J Bischoff, Matthew S SigmanAbstract:Pd-catalyzed allylic relay Suzuki cross-coupling reactions of secondary alkyl tosylates, featuring a sterically-hindered Oxidative Addition and precise control of β-hydride elimination, are reported. The identification of a linear free energy relationship between the relative rates of substrate consumption and the electronic nature of the substrate alkene suggests that the Oxidative Addition requires direct alkene involvement. A study of the effect of alkyl chain length on the reaction outcome supports a chelation-controlled Oxidative Addition.
Richard J. Puddephatt - One of the best experts on this subject based on the ideXlab platform.
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stereochemistry of Oxidative Addition of methyl iodide and hydrogen peroxide to organoplatinum ii complexes having an appended phenol group and the supramolecular chemistry of the platinum iv products
Journal of Organometallic Chemistry, 2019Co-Authors: Ava Behnia, Mahmood Azizpoor Fard, Richard J. PuddephattAbstract:Abstract The Oxidative Addition chemistry of cycloneophylplatinum (II) complexes containing ligands with an appended phenol group is reported. The platinum (II) complexes [Pt (CH2CMe2C6H4) (L)] with L = 2-C6H4NCH N-2-C6H4OH (L1) or 2-C6H4NCH2–NH-n-C6H4OH (L2, n = 2; L3, n = 3; L4, n = 4) react with MeI or H2O2 to give the corresponding platinum (IV) complexes [PtIMe(CH2CMe2C6H4) (L)] or [Pt (OH)2(CH2CMe2C6H4) (L)], respectively. NMR studies indicate that methyl iodide initially gives trans Oxidative Addition, but the initial products isomerize rapidly, often to give complex mixtures. The crystalline products all have structures with cis orientation of the PtIMe unit, whose formation is thought to require two isomerization steps after the initial Oxidative Addition. In contrast, the Oxidative Addition of H2O2 occurs with trans stereochemistry and no subsequent isomerization is observed. The iodoplatinum (IV) complexes [PtIMe(CH2CMe2C6H4) (L)] form intramolecular OH.I hydrogen bonds (L1) or intermolecular OH.I hydrogen bonds to give head-to-tail dimers (L2 or L4), or a hydrogen bond to solvent (L3). The complex [Pt (OH)2(CH2CMe2C6H4) (L4)] forms an unusual racemic supramolecular polymer with multiple OH.O and NH O hydrogen bonds.
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stereochemistry of Oxidative Addition reactions of cycloneophyl complexes of platinum ii a methylene insertion reaction from dichloromethane
Journal of Organometallic Chemistry, 2019Co-Authors: Mahmood Azizpoor Fard, Ava Behnia, Richard J. PuddephattAbstract:Abstract Unusual features are observed in studies of Oxidative Addition to cycloneophylplatinum(II) complexes [Pt(CH2CMe2C6H4)(NN)], 2, NN = 3,4,7,8-tetramethyl-1,10-phenanthroline (phen*) or 3, NN = 4,4′-di-t-butyl-2,2′-bipyridine (bubipy). The Oxidative Addition of 4-nitrobenzyl bromide to 2 or of HgCl2 to 3 occurs with cis stereochemistry to give [PtBr(CH2-4-C6H4NO2)(CH2CMe2C6H4)(phen*)] or [PtCl(HgCl)(CH2CMe2C6H4)(bubipy)], whereas similar reactions with dimethylplatinum(II) complexes occur with trans stereochemistry. The reaction of 2 with CH2Cl2 occurs, with formal insertion of methylene into the arylplatinum bond, to give [PtCl2(CH2CMe2C6H4CH2)(phen*)], the first time such a reaction has been observed with the reagent CH2Cl2. Hydrogen peroxide reacts with 2 to give Oxidative Addition with trans stereochemistry to give [Pt(OH)2(CH2CMe2C6H4)(phen*)] and reaction with chlorinated solvent then gives [PtCl(OH)(CH2CMe2C6H4)(phen*)]. Depending on the reaction conditions, the peroxyacid m-ClC6H4CO3H reacts with 2 to give [Pt(OH2)2(CH2CMe2C6H4)(phen*)](m-ClC6H4CO2)2, [{Pt(OH2)2(CH2CMe2C6H4)(phen*)}.{Pt(OH)(OH2)(CH2CMe2C6H4)(phen*)}](m-ClC6H4CO2)3, or [PtCl{OOC(=O)C6H4Cl-m}(CH2CMe2C6H4)(phen*)]. Computational studies indicate that the stereochemistry of Oxidative Addition may be determined by kinetic or thermodynamic factors in different cases, and that the unique CH2 insertion reaction with CH2Cl2 occurs by a radical mechanism. X-ray structure determinations are reported for eight of the platinum(IV) complexes.
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Oxidative Addition of Ethyl Iodide to a Dimethylplatinum(II) Complex: Unusually Large Kinetic Isotope Effects and Their Transition-State Implications
Organometallics, 2010Co-Authors: S. Masoud Nabavizadeh, Mehdi Rashidi, Sepideh Habibzadeh, Richard J. PuddephattAbstract:The mechanism of Oxidative Addition of ethyl iodide to [PtMe2(2,2′-bipyridine)], 1, has been investigated by product analysis and by study of secondary deuterium kinetic isotope effects (KIEs), usi...
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rapid reversible Oxidative Addition of group 14 halide bonds to platinum ii rates equilibria and bond energies
Journal of the American Chemical Society, 1997Co-Authors: Christopher J. Levy, Richard J. PuddephattAbstract:The reversible Oxidative Addition reactions of methyl(halogeno)tin and methyl(halogeno)germanium compounds to electron-rich platinum(II) complexes of the type [PtMe2(diimine)] have been studied. Complete kinetic and thermodynamic parameters have been obtained by VT 1H NMR for the reversible Oxidative Addition of Me3EX (E = Sn, X = Cl, Br, I) to [PtMe2(bpy-tbu2)] (bpy-tbu2 = 4,4‘-di-tert-butyl-2,2‘-bipyridyl) and related compounds, while partial data have been obtained for the reductive elimination of Me2SnCl2 from [PtClMe2(Me2SnCl)(bpy-tbu2)] and for the Oxidative Addition of Me3GeCl to [PtMe2(bpy-tbu2)]. UV−visible spectroscopic studies have also yielded equilibrium constants and ΔG° for the reversible Oxidative Addition reactions of Me3SnX (X = Cl, Br, I) to [PtMe2(diimine)]. Thermodynamic studies quantitatively establish the halogen effect on the Oxidative Addition reactions studied according to the favorability series I > Br > Cl. Kinetic studies clearly point to an SN2 mechanism for the reactions stu...
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energy profile of rapid reversible Oxidative Addition reaction
Journal of The Chemical Society Chemical Communications, 1995Co-Authors: Christopher J. Levy, Richard J. PuddephattAbstract:The trimethyltin undergo a very fast, reversible Oxidative Addition reaction with [PtMe2(Bu2bipy)], Bu2bipy = 4,4′-di-tert-butyl-2,2′-bipyridine, to give [PtXMe2(SnMe3)(Bu2bipy)] for which a complete energy profile can be obtained by using variable-temperature NMR methods; the reaction with X = I is the fastest known Oxidative Addition and activation energies when X = Cl suggest detailed structure for the transition state.
