“Homeopathic” Palladium Nanoparticle Catalysis of Cross Carbon-Carbon Coupling Reactions

Homeopathic Palladium
“Homeopathic” Palladium Nanoparticle Catalysis Deraedt and Astruc Stabilization of a PdNP by a supramolecular assembly of several G0 27-TEG dendrimers after reduction of PdII by NaBH4. The SuzukiMiyaura reaction of various bromoarenes has been carried out in H2O/EtOH media with Pd amount between 10 ppm to 0.3 ppm. Turnover numbers reached 2.7  106.71

Catalysis by palladium derivatives is now one of the most important tools in organic synthesis.

Whether researchers design palladium nanoparticles (NPs) or nanoparticles occur as palladium complexes decompose, these structures can serve as central precatalysts in common carbon-carbon bond formation.

Palladium NPs are also valuable alternatives to molecular catalysts because they do not require costly and toxic ligands. In this Account, we review the role of “homeopathic” palladium catalysts in carbon-carbon coupling reactions. Seminal studies from the groups of Beletskaya, Reetz, and de Vries showed that palladium NPs can catalyze Heck and Suzuki-Miyaura reactions with aryl iodides and, in some cases, aryl bromides at part per million levels. As a result, researchers coined the term “homeopathic” palladium catalysis. Industry has developed large-scale applications of these transformations.

In addition, chemists have used Crooks’ concept of dendrimer encapsulation to set up efficient nanofilters for Suzuki-Miyaura and selective Heck catalysis, although these transformations required high PdNP loading. With arene-centered, ferrocenyl-terminated dendrimers containing triazolyl ligands in the tethers, we designed several generations of dendrimers to compare their catalytic efficiencies, varied the numbers of Pd atoms in the PdNPs, and examined encapsulation vs stabilization. The catalytic efficiencies achieved “homeopathic” (TON = 540 000) behavior no matter the PdNP size and stabilization type. The TON increased with decreasing the Pd/substrate ratio, which suggested a leaching mechanism. Recently, we showed that water-soluble arene-centered dendrimers with tri(ethylene glycol) (TEG) tethers stabilized PdNPs involving supramolecular dendritic assemblies because of the interpenetration of the TEG branches.

Such PdNPs are stable and retain their “homeopathic” catalytic activities for Suzuki-Miyaura reactions for months. (TONs can reach 2.7 × 10(6) at 80 °C for aryl bromides and similar values for aryl iodides at 28 °C.) Sonogashira reactions catalyzed by these PdNPs are quantitative with only 0.01% Pd/mol substrate. Kato’s group has reported remarkable catalytic efficiencies for mesoporous catalysts formed by polyamidoamine (PAMAM) dendrimer polymerizations.

These and other mesoporous structures could allow for catalyst recycling, with efficiencies approaching the “homeopathic” behavior.

In recent examples of Suzuki-Miyaura reactions of aryl chlorides, chemists achieved truly “homeopathic” catalysis when a surfactant such as a tetra-n-butylammonium halide or an imidazolium salt was used in stoichiometric quantities with substrate. These results suggest that the reactive halide anion of the salt attacks the neutral Pd species to form a palladate. In the case of aryl chlorides, the reaction may occur through the difficult, rate-limiting oxidative-addition step.

“Homeopathic” Palladium Nanoparticle Catalysis of Cross Carbon-Carbon Coupling Reactions (PDF Download Available). The original article is here.

  • Nancy Siciliana

    Just writing to say what a blessing that “hide comment” key is, particularly when professional trolls pop up on your page to try and dominate the discussion. Bonus: you can block those fools from trying the same nonsense on your own page! Win win all around.

  • Nancy Siciliana

    Yes, now that we DO have the instruments to measure quantities that are much smaller (and we have the instruments to understand the importance of energy rather than simple biochemistry) the skeptics can all just shut up.

  • Christine Les Newman

    Homeopathy is like religion “have faith it is true” but all without any facts or hard evidence to support the claims but dead bodies of their adherents pile up around the world

  • Neil Kennedy

    They will never do that. They would have to find a unicorn first 🙂

  • Christine Les Newman

    Show me the peer reviewed proof backed by double blind trials

  • Neil Kennedy

    Sits well with fairy dust and unicorn spit.

  • Jonathan Light

    This is proof again that homepathic dilutions can produce scientifically measurable reactions.

  • Sundar Dias

    Palladium. Absorbs. 800 times it’s weight in hydrogen.


    HI Marie McLoughlin, this research shows that it is possible for elements to act even in the sub ppm state. As of now others claim that there is no part of the original element after the avogadro number. This disproves just that.

  • Marie McLoughlin

    “Homeopathic” in this article is misleading, where is the similar suffering? All I see is scientists utilising nanotechnology, which generally means weaponised medicine. Forgive me if I’m being thick.

  • Judith Spolander

    Doses of homeopathic remedies do not have to be high, to create a therapeutic, immune stimulating reaction in the human body!

  • Matt Zorn


  • Drmdripon Molla

    banglla nnewg pata chi