scholarly journals (DMP)DAB–Pd–MAH: A Versatile Pd(0) Source for Precatalyst Formation, Reaction Screening, and Preparative-Scale Synthesis

2021 ◽  
Author(s):  
Jingjun Huang ◽  
Matthew Isaac ◽  
Ryan Watt ◽  
Joseph Becica ◽  
Emma Dennis ◽  
...  
Keyword(s):  
Room Temperature ◽  
Cone Angle ◽  
Phosphine Ligands ◽  
Coupling Reactions ◽  
Preparative Scale ◽  
Formation Reaction ◽  
Phosphine Complexes ◽  
High Throughput Experimentation ◽  
Large Cone Angle

We report an easily prepared and bench-stable mononuclear Pd(0) source stabilized by a chelating <i>N</i>,<i>N</i>’-diaryldiazabutadiene ligand and maleic anhydride: <sup>DMP</sup>DAB–Pd–MAH. Phosphine ligands of all types, including bidentate phosphines and large cone angle biarylphosphines, rapidly and completely displace the diazabutadiene ligand at room temperature to give air-stable Pd(0) phosphine complexes. <sup>DMP</sup>DAB–Pd–MAH itself is readily soluble and stable in several organic solvents, making it an ideal Pd source for <i>in situ</i> catalyst preparation during reaction screening, as well as solution-dispensing to plate-based reaction arrays for high-throughput experimentation. Evaluation of <sup>DMP</sup>DAB–Pd–MAH alongside other common Pd(0) and Pd(II) sources in microscale reaction screens reveals that <sup>DMP</sup>DAB–Pd–MAH is superior at identifying hits across six different C–N, C–C, and C–O coupling reactions. <sup>DMP</sup>DAB–Pd–MAH, and the phosphine precatalysts derived therefrom, are also effective in preparative-scale cross couplings at low Pd loadings.

scholarly journals (DMP)DAB–Pd–MAH: A Versatile Pd(0) Source for Precatalyst Formation, Reaction Screening, and Preparative-Scale Synthesis

2021 ◽  
Author(s):  
Jingjun Huang ◽  
Matthew Isaac ◽  
Ryan Watt ◽  
Joseph Becica ◽  
Emma Dennis ◽  
...  
Keyword(s):  
Room Temperature ◽  
Cone Angle ◽  
Phosphine Ligands ◽  
Coupling Reactions ◽  
Preparative Scale ◽  
Formation Reaction ◽  
Phosphine Complexes ◽  
High Throughput Experimentation ◽  
Large Cone Angle

We report an easily prepared and bench-stable mononuclear Pd(0) source stabilized by a chelating <i>N</i>,<i>N</i>’-diaryldiazabutadiene ligand and maleic anhydride: <sup>DMP</sup>DAB–Pd–MAH. Phosphine ligands of all types, including bidentate phosphines and large cone angle biarylphosphines, rapidly and completely displace the diazabutadiene ligand at room temperature to give air-stable Pd(0) phosphine complexes. <sup>DMP</sup>DAB–Pd–MAH itself is readily soluble and stable in several organic solvents, making it an ideal Pd source for <i>in situ</i> catalyst preparation during reaction screening, as well as solution-dispensing to plate-based reaction arrays for high-throughput experimentation. Evaluation of <sup>DMP</sup>DAB–Pd–MAH alongside other common Pd(0) and Pd(II) sources in microscale reaction screens reveals that <sup>DMP</sup>DAB–Pd–MAH is superior at identifying hits across six different C–N, C–C, and C–O coupling reactions. <sup>DMP</sup>DAB–Pd–MAH, and the phosphine precatalysts derived therefrom, are also effective in preparative-scale cross couplings at low Pd loadings.

AdBippyPhos Promotes Pd-Catalyzed C–N Coupling Between Weakly Nucleophilic Sulfonamides and Heteroaryl Halides

2019 ◽  
Author(s):  
Joseph Becica ◽  
Damian Hruszkewycz ◽  
Janelle Steves ◽  
Jennifer Elward ◽  
David Leitch ◽  
...  
Keyword(s):  
High Throughput ◽  
Medicinal Chemistry ◽  
Cone Angle ◽  
Catalyst System ◽  
Coupling Reactions ◽  
Potential Importance ◽  
High Throughput Experimentation ◽  
Large Cone Angle ◽  
General Method

Sulfonamides are poor nucleophiles in Pd C-N coupling catalysis, hindering synthesis of densely-functionalized N,N-diaryl sulfonamide motifs relevant to medicinal chemistry. Through targeted high-throughput experimentation (HTE), we have identified the Pd/AdBippyPhos catalyst system as an effective and general method to construct this difficult to access moiety. In particular, AdBippyPhos is critical for the installation of heteroaromatic groups. Computational steric parameterization of the investigated ligands reveals the potential importance of remote steric demand, where a large cone angle combined with an accessible Pd center is correlated to successful catalysts for C-N coupling reactions.<br>

scholarly journals High-Throughput Discovery and Evaluation of a General Catalytic Method for N-Arylation of Weakly Nucleophilic Sulfonamides

2019 ◽  
Author(s):  
Joseph Becica ◽  
Damian Hruszkewycz ◽  
Janelle Steves ◽  
Jennifer Elward ◽  
David Leitch ◽  
...  
Keyword(s):  
High Throughput ◽  
Medicinal Chemistry ◽  
Cone Angle ◽  
Catalyst System ◽  
Coupling Reactions ◽  
Potential Importance ◽  
Catalytic Method ◽  
High Throughput Experimentation ◽  
Large Cone Angle ◽  
General Method

Sulfonamides are poor nucleophiles in Pd C-N coupling catalysis, hindering synthesis of densely-functionalized N,N-diaryl sulfonamide motifs relevant to medicinal chemistry. Through targeted high-throughput experimentation (HTE), we have identified the Pd/AdBippyPhos catalyst system as an effective and general method to construct this difficult to access moiety. In particular, AdBippyPhos is critical for the installation of heteroaromatic groups. Computational steric parameterization of the investigated ligands reveals the potential importance of remote steric demand, where a large cone angle combined with an accessible Pd center is correlated to successful catalysts for C-N coupling reactions.<br>

scholarly journals High-Throughput Discovery and Evaluation of a General Catalytic Method for N-Arylation of Weakly Nucleophilic Sulfonamides

2019 ◽  
Author(s):  
Joseph Becica ◽  
Damian Hruszkewycz ◽  
Janelle Steves ◽  
Jennifer Elward ◽  
David Leitch ◽  
...  
Keyword(s):  
High Throughput ◽  
Medicinal Chemistry ◽  
Cone Angle ◽  
Catalyst System ◽  
Coupling Reactions ◽  
Potential Importance ◽  
Catalytic Method ◽  
High Throughput Experimentation ◽  
Large Cone Angle ◽  
General Method

Sulfonamides are poor nucleophiles in Pd C-N coupling catalysis, hindering synthesis of densely-functionalized N,N-diaryl sulfonamide motifs relevant to medicinal chemistry. Through targeted high-throughput experimentation (HTE), we have identified the Pd/AdBippyPhos catalyst system as an effective and general method to construct this difficult to access moiety. In particular, AdBippyPhos is critical for the installation of heteroaromatic groups. Computational steric parameterization of the investigated ligands reveals the potential importance of remote steric demand, where a large cone angle combined with an accessible Pd center is correlated to successful catalysts for C-N coupling reactions.<br>

An easily prepared palladium-hydrogel nanocomposite catalyst for C–C coupling reactions

2014 ◽  
Vol 2 (44) ◽  
pp. 18952-18958 ◽  
Author(s):  
Mitasree Maity ◽  
Uday Maitra
Keyword(s):  
Palladium Nanoparticles ◽  
Room Temperature ◽  
Coupling Reaction ◽  
Coupling Reactions ◽  
Sodium Cyanoborohydride ◽  
Efficient Catalyst ◽  
Suzuki Coupling Reaction ◽  
Reaction In Water ◽  
Hydrogel Nanocomposite

Palladium nanoparticles were efficiently prepared in situ by sodium cyanoborohydride reduction of Pd(ii) at room temperature using calcium-cholate hydrogel fibers as templates. The PdNPs self-organize on the gel fibers, which supports the controlled growth as well as stabilization of PdNPs. The hybrid xerogel was used as an efficient catalyst for the Suzuki coupling reaction in water.

Monophosphine Ligands Promote Pd-Catalyzed C–S Cross-Coupling Reactions at Room Temperature with Soluble Bases

2019 ◽  
Author(s):  
Jessica Xu ◽  
Richard Liu ◽  
Charles Yeung ◽  
Stephen L. Buchwald
Keyword(s):  
Transition Metals ◽  
Room Temperature ◽  
Reliable Method ◽  
Cross Coupling ◽  
Phosphine Ligands ◽  
Coupling Reactions ◽  
Late Transition Metals ◽  
Cross Coupling Reactions ◽  
Agricultural Applications ◽  
Late Transition

<div> <p>The Pd-catalyzed cross-coupling of thiols with aromatic electrophiles is a reliable method for the synthesis of aryl thioethers, which are important compounds for pharmaceutical and agricultural applications. Since thiols and thiolates strongly bind late transition metals, previous research has focused on catalysts supported by chelating, bisphosphine ligands, which were considered less likely to be displaced during the course of the reaction. We show that by using monophosphine ligands instead, more effective catalysis can be achieved. Notably, compared to previous methods, this increased reactivity allows for the use of much lower reaction temperature, soluble bases, and base-sensitive substrates. In contrast to conventional wisdom, our mechanistic data suggest that the extent of displacement of phosphine ligands by thiols is, firstly, not correlated with the ligand bulk or thiol nucleophilicity, and secondly, not predictive of the effectiveness of a given ligand in combination with palladium.</p> </div>

Monophosphine Ligands Promote Pd-Catalyzed C–S Cross-Coupling Reactions at Room Temperature with Soluble Bases

2019 ◽  
Author(s):  
Jessica Xu ◽  
Richard Liu ◽  
Charles Yeung ◽  
Stephen L. Buchwald
Keyword(s):  
Transition Metals ◽  
Room Temperature ◽  
Reliable Method ◽  
Cross Coupling ◽  
Phosphine Ligands ◽  
Coupling Reactions ◽  
Late Transition Metals ◽  
Cross Coupling Reactions ◽  
Agricultural Applications ◽  
Late Transition

<div> <p>The Pd-catalyzed cross-coupling of thiols with aromatic electrophiles is a reliable method for the synthesis of aryl thioethers, which are important compounds for pharmaceutical and agricultural applications. Since thiols and thiolates strongly bind late transition metals, previous research has focused on catalysts supported by chelating, bisphosphine ligands, which were considered less likely to be displaced during the course of the reaction. We show that by using monophosphine ligands instead, more effective catalysis can be achieved. Notably, compared to previous methods, this increased reactivity allows for the use of much lower reaction temperature, soluble bases, and base-sensitive substrates. In contrast to conventional wisdom, our mechanistic data suggest that the extent of displacement of phosphine ligands by thiols is, firstly, not correlated with the ligand bulk or thiol nucleophilicity, and secondly, not predictive of the effectiveness of a given ligand in combination with palladium.</p> </div>

scholarly journals Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

2016 ◽  
Vol 12 ◽  
pp. 1040-1064 ◽  
Author(s):  
Takashi Nishikata ◽  
Alexander R Abela ◽  
Shenlin Huang ◽  
Bruce H Lipshutz
Keyword(s):  
Room Temperature ◽  
Plant Pathogens ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
Arylboronic Acid ◽  
Aryl Iodide ◽  
Horticultural Crops ◽  
Cross Coupling Reactions ◽  
Cationic Palladium

Cationic palladium(II) complexes have been found to be highly reactive towards aromatic C–H activation of arylureas at room temperature. A commercially available catalyst [Pd(MeCN)4](BF4)2 or a nitrile-free cationic palladium(II) complex generated in situ from the reaction of Pd(OAc)2 and HBF4, effectively catalyzes C–H activation/cross-coupling reactions between aryl iodides, arylboronic acids and acrylates under milder conditions than those previously reported. The nature of the directing group was found to be critical for achieving room temperature conditions, with the urea moiety the most effective in promoting facile coupling reactions at an ortho C–H position. This methodology has been utilized in a streamlined and efficient synthesis of boscalid, an agent produced on the kiloton scale annually and used to control a range of plant pathogens in broadacre and horticultural crops. Mechanistic investigations led to a proposed catalytic cycle involving three steps: (1) C–H activation to generate a cationic palladacycle; (2) reaction of the cationic palladacycle with an aryl iodide, arylboronic acid or acrylate, and (3) regeneration of the active cationic palladium catalyst. The reaction between a cationic palladium(II) complex and arylurea allowed the formation and isolation of the corresponding palladacycle intermediate, characterized by X-ray analysis. Roles of various additives in the stepwise process have also been studied.

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