225931-80-6Relevant articles and documents
Water-Soluble Palladium Reagents for Cysteine S-Arylation under Ambient Aqueous Conditions
Rojas, Anthony J.,Pentelute, Bradley L.,Buchwald, Stephen L.
, p. 4263 - 4266 (2017)
We report the use of a sulfonated biarylphosphine ligand (sSPhos) to promote the chemoselective modification of cysteine containing proteins and peptides with palladium reagents in aqueous medium. The use of sSPhos allowed for the isolation of several air-stable and water-soluble mono- and bis-palladium reagents, which were used in an improved protocol for the rapid S-arylation of cysteines under benign and physiologically relevant conditions. The cosolvent-free aqueous conditions were applied to the conjugation of a variety of biomolecules with affinity tags, heterocycles, fluorophores, and functional handles. Additionally, bis-palladium reagents were used to perform macrocyclization of peptides bearing two cysteine residues.
Palladium Oxidative Addition Complexes for Peptide and Protein Cross-linking
Kubota, Koji,Dai, Peng,Pentelute, Bradley L.,Buchwald, Stephen L.
, p. 3128 - 3133 (2018)
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.
A Neophyl Palladacycle as an Air- And Thermally Stable Precursor to Oxidative Addition Complexes
Buchwald, Stephen L.,King, Ryan P.,Krska, Shane W.
supporting information, p. 7927 - 7932 (2021/10/25)
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 Cámpora'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.
Palladium-Catalyzed Synthesis of α-Carbonyl-α′-(hetero)aryl Sulfoxonium Ylides: Scope and Insight into the Mechanism
Janot, Christopher,Chagnoleau, Jean-Baptiste,Halcovitch, Nathan R.,Muir, James,A?ssa, Christophe
, p. 1126 - 1137 (2019/12/30)
Despite recent advances, a general method for the synthesis of α-carbonyl-α′-(hetero)aryl sulfoxonium ylides is needed to benefit more greatly from the potential safety advantages offered by these compounds over the parent diazo compounds. Herein, we report the palladium-catalyzed cross-coupling of aryl bromides and triflates with α-carbonyl sulfoxonium ylides. We also report the use of this method for the modification of an active pharmaceutical ingredient and for the synthesis of a key precursor of antagonists of the neurokinin-1 receptor. In addition, the mechanism of the reaction was inferred from several observations. Thus, the oxidative addition complex [(XPhos)PhPdBr] and its dimer were observed by 31P{1H} NMR, and these complexes were shown to be catalytically and kinetically competent. Moreover, a complex resulting from the transmetalation of [(XPhos)ArPdBr] (Ar = p-CF3-C6H4) with a model sulfoxonium ylide was observed by mass spectrometry. Finally, the partial rate law suggests that the transmetalation and the subsequent deprotonation are rate-determining in the catalytic cycle.
Carboxylation of Aryl Triflates with CO2 Merging Palladium and Visible-Light-Photoredox Catalysts
Bhunia, Samir Kumar,Das, Pritha,Nandi, Shantanu,Jana, Ranjan
supporting information, p. 4632 - 4637 (2019/06/27)
We report herein a visible-light-promoted, highly practical carboxylation of readily accessible aryl triflates at ambient temperature and a balloon pressure of CO2 by the combined use of palladium and photoredox Ir(III) catalysts. Strikingly, the stoichiometric metallic reductant is replaced by a nonmetallic amine reductant providing an environmentally benign carboxylation process. In addition, one-pot synthesis of a carboxylic acid directly from phenol and modification of estrone and concise synthesis of pharmaceutical drugs adapalene and bexarotene have been accomplished via late-stage carboxylation reaction. Furthermore, a parallel decarboxylation-carboxylation reaction has been demonstrated in an H-type closed vessel that is an interesting concept for the strategic sector. Spectroscopic and spectroelectrochemical studies indicated electron transfer from the Ir(III)/DIPEA combination to generate aryl carboxylate and Pd(0) for catalytic turnover.
Photoaffinity palladium reagents for capture of protein-protein interactions
Zheng, Qizhen,Pang, Zhengyuan,Liu, Jingwei,Zhou, Yi,Sun, Yang,Yin, Zheng,Lou, Zhiyong
supporting information, p. 6369 - 6373 (2019/07/09)
Protein-protein interactions (PPIs) are indispensable in almost all cellular processes. Probing of complex PPIs provides new insights into the biological system of interest and paves the way for the development of therapeutics. Herein, we report a strategy for the capture of protein-protein interactions using photoaffinity palladium reagents. First, the palladium-mediated reagent site specifically transferred a photoaffinity modified aryl group to the designated cysteine residue. Next, the photoaffinity group was activated by UV radiation to trap the proximal protein residue for the formation of a crosslink. This strategy was used to capture the PYL-ABA-PP2C interaction, which is at the core of the abscisic acid (ABA) signalling pathway. Our results indicated that this palladium-mediated strategy can serve as an alternative for incorporating an increasing number of diverse substrates for protein crosslinking through cysteine modifications and can be explored for use in mapping protein-peptide or protein-protein interaction surfaces and in trapping potential interacting partners.
Evidence for single-electron pathways in the reaction between palladium(II) dialkyl complexes and alkyl bromides under thermal and photoinduced conditions
Andersen, Thomas L.,Kramer, S?ren,Overgaard, Jacob,Skrydstrup, Troels
supporting information, p. 2058 - 2066 (2017/06/19)
Palladium(II) dialkyl complexes have previously been studied for their formation of alkanes through reductive elimination. More recently, these complexes, especially L2Pd(CH2TMS)2 derived from Pd(COD)(CH2TMS)2, have found general use as palladium(0) precursors for stoichiometric formation of oxidative addition complexes through a two-electron reductive elimination/oxidative addition sequence. Herein, we report evidence for an alternative pathway, proceeding through single-electron elementary steps, when DPEPhosPd(CH2TMS)2 is treated with an α-bromo-α,α-difluoroacetamide. This new pathway does not take place through a palladium(0) intermediate, neither does it afford the expected oxidative addition complexes. Instead, stoichiometric amounts of carbon-centered alkyl radicals are formed, which can be trapped in high yields either by TEMPO or by an arene, leading to α-aryl-α,α-difluoroacetamides. The same overall transformation takes place under both thermal conditions (70 °C) and irradiation with a household light bulb (at 30 °C). It is also demonstrated that DPEPhosPdMe2, made in situ from Pd(TMEDA)Me2, displays a similar initial reactivity. Finally, electronically and structurally different alkyl bromides were evaluated as reaction partners.
An improved catalyst system for the Pd-catalyzed fluorination of (hetero)aryl triflates
Lee, Hong Geun,Milner, Phillip J.,Buchwald, Stephen L.
supporting information, p. 5602 - 5605 (2013/11/19)
The stable Pd(0) species [(1,5-cyclooctadiene)(L·Pd)2] (L = AdBrettPhos) has been prepared and successfully evaluated as a precatalyst for the fluorination of aryl triflates derived from biologically active and heteroaryl phenols, challenging substrates for our previously reported catalyst system. Additionally, this precatalyst activates at room temperature under neutral conditions, generates 1,5-cyclooctadiene as the only byproduct, and leads to overall cleaner reaction profiles.
Syntheses and spectroscopic characteristics of dialkylpalladium(II) complexes; PdR2(cod) as precursors for derivatives with N- or P-donor ligands
Pan, Yi,Young, G. Brent
, p. 257 - 264 (2007/10/03)
Cycloocta-1,5-diene dialkylpalladium(II) derivatives, PdR2(cod), (R=CH2SiMe3, CH2SiMe2Ph) have been isolated and used conveniently as precursors in the preparation of dialkylpalladium complexes, PdRs
