Heterogeneous metal catalyzed cross-coupling

Last updated

Heterogeneous metal catalyzed cross-coupling is a subset of metal catalyzed cross-coupling in which a heterogeneous metal catalyst is employed. Generally heterogeneous cross-coupling catalysts consist of a metal dispersed on an inorganic surface or bound to a polymeric support with ligands. Heterogeneous catalysts provide potential benefits over homogeneous catalysts in chemical processes in which cross-coupling is commonly employed—particularly in the fine chemical industry—including recyclability and lower metal contamination of reaction products. [1] However, for cross-coupling reactions, heterogeneous metal catalysts can suffer from pitfalls such as poor turnover and poor substrate scope, which have limited their utility in cross-coupling reactions to date relative to homogeneous catalysts. [2] Heterogeneous metal catalyzed cross-couplings, as with homogeneous metal catalyzed ones, most commonly use Pd as the cross-coupling metal.

Contents


Reaction mechanism and implications

Pd-catalyzed cross-coupling reactions catalyzed by a heterogeneous catalyst are thought to generally proceed, not on the surface of the solid catalyst, but in the solution phase. [3] The solution-phase intermediates are not necessarily distinguishable from those obtained during homogeneous cross-couplings – for example, a heterogeneous Pd-catalyzed Suzuki reaction still proceeds via oxidative addition of the electrophile by Pd(0), transmetallation of a boronate, and reductive elimination to give product and regenerate Pd(0) (Figure 1A). The activity of heterogeneous catalysts in cross-coupling seems to be tied to the ability of the electrophile (usually an aryl halide) to undergo oxidative addition with an atom of Pd(0), whether on the solid catalyst surface or already in solution, after which the rest of the catalytic cycle will take place – in solution.

Figure 1. Mechanism for a generic cross-coupling reaction with A) homogenous Pd in the presence of a ligand and B) heterogeneous, ligandless Pd as the Pd source. Fig1final homovshetero.png
Figure 1. Mechanism for a generic cross-coupling reaction with A) homogenous Pd in the presence of a ligand and B) heterogeneous, ligandless Pd as the Pd source.

The role of the solid phase in heterogeneous metal catalyzed cross-coupling, then, is more subtle than one might expect. Rather than enabling the productive catalytic cycle, the solid phase acts as a reservoir of Pd that is accessible to the productive catalytic cycle. For heterogeneous catalytic cross-coupling which involves unligated Pd (for example, when Pd/C is used as the catalyst), there exists a significant equilibrium that partitions Pd(0) between atomic, solution-phase monomers, surface-bound Pd, colloidal Pd and higher order Pd aggregates (Figure 1B). Aggregation of Pd atoms into clusters ultimately leads to irreversible precipitation of insoluble metallic Pd, which limits the maximum turnover number that can be achieved. An effective heterogeneous cross-coupling catalyst will recapture monomeric Pd or lower order oligomers and colloids onto the solid phase in order to maintain low concentrations of these species in solution, disfavouring aggregation and favouring instead the productive elementary steps of cross-coupling. [4] This may explain the (perhaps counterintuitive) observation that lower catalyst loadings can improve turnover number for a heterogeneous cross-coupling catalyst system (Pd on porous glass, in the Heck reactions of 4-bromoacetophenone at 180 °C). [5]

The solid-phase to solution-phase mass transfer requirement for Pd in most heterogeneous cross-couplings has further implications. Because the supported ligand for a polymer-supported catalyst is not optimized for reactivity, and because the productive catalytic cycle usually ignores the supported ligand entirely even if present, “difficult” cross-coupling reactions which require fine tuning of the electronic and steric properties of the Pd catalyst – via expensive, designer ligands – are scarcely reported in a heterogeneous context. A 2021 survey of heterogeneous metal catalyzed cross-couplings in the fine chemical industry reported, out of 22 examples, 19 Suzuki or Heck reactions, which included only 2 examples with N-basic heterocycles, and only 4 examples with a singly-ortho-substituted electrophile (representative example in Scheme 1). [1] In nearly all these cases, reactions were initially developed with a homogeneous Pd catalyst (typically Pd(OAc)2 with either no exogenous ligand or PPh3 as ligand) on smaller scale, and only evaluated with heterogeneous Pd catalysts, (typically Pd/C or Pd black) for scaleup to decagram to multi-hundred-kilo scales, once process considerations such as process mass intensity and separation costs became significant. Notably, no polymer-supported catalysts were used; for these real-world examples of heterogeneous catalytic cross-coupling on scale, inorganic heterogeneous catalysts (such as Pd/C) are far cheaper and more robust than polymer-supported ligated Pd catalysts, and thus more commonly employed.

Scheme 1. Pd/C catalyzed cross coupling performed on 2.5 kg scale in 85% yield with <10 ppm residual Pd following filtration and DMF washing. Fig10 scheme.png
Scheme 1. Pd/C catalyzed cross coupling performed on 2.5 kg scale in 85% yield with <10 ppm residual Pd following filtration and DMF washing.

When designing a polymer-ligand solid support for Pd, the ligands should not simply be immobilized variants of homogeneous ligands which effect catalysis in the presence of Pd. Rather, immobilized ligands should optimize the redeposition of Pd onto the solid phase at the end of each catalytic cycle in a catalytically active form that is ready for a subsequent catalytic cycle. [6] Ligand sets which are rarely seen in homogeneous cross-coupling, then, appear in heterogeneous ligand-containing Pd catalysts. For example, Buchmeiser et al. have reported high turnover N,N-bidentate ligands (Figure 2) which achieve turnover numbers (TONs) of >105 in the Heck reactions of iodobenzene, and TON ca. 103 in the amination of bromobenzene. [7] These TONs are competitive with even the best solution TONs, giving clear advantages for this system for separation of the product from catalyst post-reaction.

Figure 2. A high-turnover N,N-supported Pd complex. Fig2final nnbidentateligand.png
Figure 2. A high-turnover N,N-supported Pd complex.

Kinetics

The “shuttling” kinetics of Pd mass transfer (from solid phase to solution phase and back to solid phase) have been verified by three-phase test experiments, [8] while the solution-phase catalytic activity which characterizes most heterogeneous cross-coupling has been verified by TEM, hot filtration, and poisoning experiments. [9] [10] However, truly heterogeneous cross-coupling systems may exist. Poyatos et al. immobilized a Pd pincer carbene complex (Figure 3) on MK-10 clay and observed that while high TON (ca. 103) and TOF was maintained relative to the soluble catalyst, no activity was found in the solution for the supported catalyst – a strong indicator of a fully heterogeneous catalytic mechanism. [11]

Figure 3. A Pd pincer carbene complex which may operate via a fully heterogeneous mechanism when immobilized. Fig3final pincer.png
Figure 3. A Pd pincer carbene complex which may operate via a fully heterogeneous mechanism when immobilized.

Heterogeneous metal catalyzed cross-coupling in flow vs batch

For batch cross-couplings which use immobilized Pd, the concentration of solution-phase Pd increases dramatically when the reaction commences (as Pd is transferred out of the solid phase), and has decreased dramatically by the time full conversion has been achieved (by readsorption or precipitation onto the solid support). [12] [13] Such a kinetic profile matches the processing requirements of a batch process – although some amount of metal remains in solution post-reaction, the supported Pd catalyst can usually be recycled several times, despite the limitations described above.

In contrast, continuous flow systems do not allow for effective metal redeposition on the solid support; the reaction stream will transport the Pd through the support due to continuous metal leaching/readsorption (Figure 4). Cumulative periods of operation inevitably result in significant metal leaching from the flow system, depleting the supported catalyst's activity and giving low recyclability, with – typically – no particular benefit for reactivity. [14]

Figure 4. Heterogeneous Pd catalyzed cross-couplings in A) batch vs B) flow. Fig4final batch vs flow.png
Figure 4. Heterogeneous Pd catalyzed cross-couplings in A) batch vs B) flow.

In principle, it is possible for the metal leaching inherent to continuous flow cross-coupling to be avoided. Plucinkski and coworkers developed a continuous Mizoroki-Heck and hydrogenation sequence consisting of two separated packed-bed reactors containing Pd/C. [15] Because the Pd/C-catalyzed hydrogenation proceeds via a heterogeneous mechanism, [16] metal leaching due to the second hydrogenation step is minimal, and Pd leached from the first part of the reactor during the Heck coupling can be recaptured by the second packed bed during the hydrogenation. By cycling the direction of flow between forward and reverse, catalytic activity could be maintained over two consecutive experiments, although a greater number of cycles would be desirable in order to vindicate this strategy for increasing turnover in solid-supported flow catalysts for cross-coupling.

Separation

Heterogeneous catalysts are easily removed from a reaction mixture by filtration. Although some amount of metal catalyst typically remains in the product from leaching, these amounts tend to be lower than those remaining after workup of a homogenous metal-catalyzed cross-coupling. [1]

Magnetic removal

A heterogeneous catalyst consisting of Pd supported by silica-coated Fe2O3/Fe3O4 nanoparticles allows the reaction to be heated by electrical induction, and also allows facile magnetic separation of catalyst and product post-reaction. [17] Copper ferrite has been reported as a heterocycle arylation catalyst and can be similarly separated from the reaction with a magnet. [18]

Recycling

Heterogeneous cross-coupling catalysts typically lose some portion of activity to metal leaching between different runs as a result of the solution-phase catalytic cycle (see above), and hence can only be recycled a finite number of times. [19]

Multiple groups [19] [20] have pointed out that the need for recycling is obviated at extremely high turnover and low catalyst loading, since in these cases the catalyst cost is negligible relative to the cost of other reaction components. As a result, for most cross-coupling reactions, in which heterogeneous catalysts generally require higher loadings than equivalent homogeneous ones, the benefits of heterogeneous catalysts afforded by the greater ease of recycling may be outweighed by the disadvantages – higher catalyst loadings, and the additional process costs. Additionally, when catalyst loadings are lower than 10 ppm – the regulatory limit for several metals including Pd in pharmaceutical APIs – separation of the metal following the reaction does not even need to be performed. This nullifies another of the commonly perceived advantages of heterogeneous catalysts over their homogeneous counterparts.

Related Research Articles

<span class="mw-page-title-main">Catalysis</span> Process of increasing the rate of a chemical reaction

Catalysis is the process of change in rate of a chemical reaction by adding a substance known as a catalyst. Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quickly, very small amounts of catalyst often suffice; mixing, surface area, and temperature are important factors in reaction rate. Catalysts generally react with one or more reactants to form intermediates that subsequently give the final reaction product, in the process of regenerating the catalyst.

<span class="mw-page-title-main">Hydrogenation</span> Chemical reaction between molecular hydrogen and another compound or element

Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic compounds. Hydrogenation typically constitutes the addition of pairs of hydrogen atoms to a molecule, often an alkene. Catalysts are required for the reaction to be usable; non-catalytic hydrogenation takes place only at very high temperatures. Hydrogenation reduces double and triple bonds in hydrocarbons.

The Heck reaction is the chemical reaction of an unsaturated halide with an alkene in the presence of a base and a palladium catalyst to form a substituted alkene. It is named after Tsutomu Mizoroki and Richard F. Heck. Heck was awarded the 2010 Nobel Prize in Chemistry, which he shared with Ei-ichi Negishi and Akira Suzuki, for the discovery and development of this reaction. This reaction was the first example of a carbon-carbon bond-forming reaction that followed a Pd(0)/Pd(II) catalytic cycle, the same catalytic cycle that is seen in other Pd(0)-catalyzed cross-coupling reactions. The Heck reaction is a way to substitute alkenes.

The Suzuki reaction is an organic reaction, classified as a cross-coupling reaction, where the coupling partners are a boronic acid and an organohalide and the catalyst is a palladium(0) complex. It was first published in 1979 by Akira Suzuki, and he shared the 2010 Nobel Prize in Chemistry with Richard F. Heck and Ei-ichi Negishi for their contribution to the discovery and development of palladium-catalyzed cross-couplings in organic synthesis. This reaction is also known as the Suzuki–Miyaura reaction or simply as the Suzuki coupling. It is widely used to synthesize polyolefins, styrenes, and substituted biphenyls. Several reviews have been published describing advancements and the development of the Suzuki reaction. The general scheme for the Suzuki reaction is shown below, where a carbon-carbon single bond is formed by coupling a halide (R1-X) with an organoboron species (R2-BY2) using a palladium catalyst and a base. The organoboron species is usually synthesized by hydroboration or carboboration, allowing for rapid generation of molecular complexity.

The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vinyl halide.

<span class="mw-page-title-main">Transition metal pincer complex</span>

In chemistry, a transition metal pincer complex is a type of coordination complex with a pincer ligand. Pincer ligands are chelating agents that binds tightly to three adjacent coplanar sites in a meridional configuration. The inflexibility of the pincer-metal interaction confers high thermal stability to the resulting complexes. This stability is in part ascribed to the constrained geometry of the pincer, which inhibits cyclometallation of the organic substituents on the donor sites at each end. In the absence of this effect, cyclometallation is often a significant deactivation process for complexes, in particular limiting their ability to effect C-H bond activation. The organic substituents also define a hydrophobic pocket around the reactive coordination site. Stoichiometric and catalytic applications of pincer complexes have been studied at an accelerating pace since the mid-1970s. Most pincer ligands contain phosphines. Reactions of metal-pincer complexes are localized at three sites perpendicular to the plane of the pincer ligand, although in some cases one arm is hemi-labile and an additional coordination site is generated transiently. Early examples of pincer ligands were anionic with a carbanion as the central donor site and flanking phosphine donors; these compounds are referred to as PCP pincers.

<span class="mw-page-title-main">Palladium(II) acetate</span> Chemical compound

Palladium(II) acetate is a chemical compound of palladium described by the formula [Pd(O2CCH3)2]n, abbreviated [Pd(OAc)2]n. It is more reactive than the analogous platinum compound. Depending on the value of n, the compound is soluble in many organic solvents and is commonly used as a catalyst for organic reactions.

Nanomaterial-based catalysts are usually heterogeneous catalysts broken up into metal nanoparticles in order to enhance the catalytic process. Metal nanoparticles have high surface area, which can increase catalytic activity. Nanoparticle catalysts can be easily separated and recycled. They are typically used under mild conditions to prevent decomposition of the nanoparticles.

The Negishi coupling is a widely employed transition metal catalyzed cross-coupling reaction. The reaction couples organic halides or triflates with organozinc compounds, forming carbon-carbon bonds (C-C) in the process. A palladium (0) species is generally utilized as the metal catalyst, though nickel is sometimes used. A variety of nickel catalysts in either Ni0 or NiII oxidation state can be employed in Negishi cross couplings such as Ni(PPh3)4, Ni(acac)2, Ni(COD)2 etc.

In organic chemistry, the Kumada coupling is a type of cross coupling reaction, useful for generating carbon–carbon bonds by the reaction of a Grignard reagent and an organic halide. The procedure uses transition metal catalysts, typically nickel or palladium, to couple a combination of two alkyl, aryl or vinyl groups. The groups of Robert Corriu and Makoto Kumada reported the reaction independently in 1972.

Asymmetric hydrogenation is a chemical reaction that adds two atoms of hydrogen to a target (substrate) molecule with three-dimensional spatial selectivity. Critically, this selectivity does not come from the target molecule itself, but from other reagents or catalysts present in the reaction. This allows spatial information to transfer from one molecule to the target, forming the product as a single enantiomer. The chiral information is most commonly contained in a catalyst and, in this case, the information in a single molecule of catalyst may be transferred to many substrate molecules, amplifying the amount of chiral information present. Similar processes occur in nature, where a chiral molecule like an enzyme can catalyse the introduction of a chiral centre to give a product as a single enantiomer, such as amino acids, that a cell needs to function. By imitating this process, chemists can generate many novel synthetic molecules that interact with biological systems in specific ways, leading to new pharmaceutical agents and agrochemicals. The importance of asymmetric hydrogenation in both academia and industry contributed to two of its pioneers — William Standish Knowles and Ryōji Noyori — being awarded one half of the 2001 Nobel Prize in Chemistry.

In organic chemistry, a cross-coupling reaction is a reaction where two different fragments are joined. Cross-couplings are a subset of the more general coupling reactions. Often cross-coupling reactions require metal catalysts. One important reaction type is this:

Organogold chemistry is the study of compounds containing gold–carbon bonds. They are studied in academic research, but have not received widespread use otherwise. The dominant oxidation states for organogold compounds are I with coordination number 2 and a linear molecular geometry and III with CN = 4 and a square planar molecular geometry.

<span class="mw-page-title-main">Catalyst support</span> Porous material with a high specific surface area supporting a catalyst

In chemistry, a catalyst support is the material, usually a solid with a high surface area, to which a catalyst is affixed. The activity of heterogeneous catalysts is mainly promoted by atoms present at the accessible surface of the material. Consequently, great effort is made to maximize the specific surface area of a catalyst. One popular method for increasing surface area involves distributing the catalyst over the surface of the support. The support may be inert or participate in the catalytic reactions. Typical supports include various kinds of activated carbon, alumina, and silica.

<span class="mw-page-title-main">PEPPSI</span> Group of chemical compounds

PEPPSI is an abbreviation for pyridine-enhanced precatalyst preparation stabilization and initiation. It refers to a family of commercially available palladium catalysts developed around 2005 by Prof. Michael G. Organ and co-workers at York University, which can accelerate various carbon-carbon and carbon-heteroatom bond forming cross-coupling reactions. In comparison to many alternative palladium catalysts, Pd-PEPPSI-type complexes are stable to air and moisture and are relatively easy to synthesize and handle.

Decarboxylative cross coupling reactions are chemical reactions in which a carboxylic acid is reacted with an organic halide to form a new carbon-carbon bond, concomitant with loss of CO2. Aryl and alkyl halides participate. Metal catalyst, base, and oxidant are required.

<span class="mw-page-title-main">Palladium–NHC complex</span>

In organometallic chemistry, palladium-NHC complexes are a family of organopalladium compounds in which palladium forms a coordination complex with N-heterocyclic carbenes (NHCs). They have been investigated for applications in homogeneous catalysis, particularly cross-coupling reactions.

Dialkylbiaryl phosphine ligands are phosphine ligands that are used in homogeneous catalysis. They have proved useful in Buchwald-Hartwig amination and etherification reactions as well as Negishi cross-coupling, Suzuki-Miyaura cross-coupling, and related reactions. In addition to these Pd-based processes, their use has also been extended to transformations catalyzed by nickel, gold, silver, copper, rhodium, and ruthenium, among other transition metals.

Palladacycle, as a class of metallacycles, refers to complexes containing at least one carbon-palladium bond. Palladacycles are invoked as intermediates in catalytic or palladium mediated reactions. They have been investigated as pre-catalysts for homogeneous catalysis and synthesis.

Heterobimetallic catalysis is an approach to catalysis that employs two different metals to promote a chemical reaction. Included in this definition are cases where: 1) each metal activates a different substrate, 2) both metals interact with the same substrate, and 3) only one metal directly interacts with the substrate(s), while the second metal interacts with the first.

References

  1. 1 2 3 Vásquez-Céspedes, Suhelen; Betori, Rick C.; Cismesia, Megan A.; Kirsch, Janelle K.; Yang, Qiang (2021-04-16). "Heterogeneous Catalysis for Cross-Coupling Reactions: An Underutilized Powerful and Sustainable Tool in the Fine Chemical Industry?". Organic Process Research & Development. 25 (4): 740–753. doi:10.1021/acs.oprd.1c00041. ISSN   1083-6160. S2CID   233613527.
  2. ↑ Hübner, Sandra; de Vries, Johannes G.; Farina, Vittorio (2016-01-07). "Why Does Industry Not Use Immobilized Transition Metal Complexes as Catalysts?". Advanced Synthesis & Catalysis. 358 (1): 3–25. doi:10.1002/adsc.201500846.
  3. ↑ Biffis, Andrea; Zecca, Marco; Basato, Marino (September 2001). "Palladium metal catalysts in Heck CC coupling reactions". Journal of Molecular Catalysis A: Chemical. 173 (1–2): 249–274. doi:10.1016/S1381-1169(01)00153-4.
  4. ↑ de Vries, André H. M.; Mulders, Jan M. C. A.; Mommers, John H. M.; Henderickx, Huub J. W.; de Vries, Johannes G. (2003-09-01). "Homeopathic Ligand-Free Palladium as a Catalyst in the Heck Reaction. A Comparison with a Palladacycle". Organic Letters. 5 (18): 3285–3288. doi:10.1021/ol035184b. ISSN   1523-7060. PMID   12943408.
  5. ↑ Li, Jintong; Mau, Albert W.-H.; Strauss, Christopher R. (1997). "The use of palladium on porous glass for catalytic coupling reactions". Chemical Communications (14): 1275–1276. doi:10.1039/a702457f.
  6. ↑ Zhao, Fengyu; Shirai, Masayuki; Ikushima, Yutaka; Arai, Masahiko (March 2002). "The leaching and re-deposition of metal species from and onto conventional supported palladium catalysts in the Heck reaction of iodobenzene and methyl acrylate in N-methylpyrrolidone". Journal of Molecular Catalysis A: Chemical. 180 (1–2): 211–219. doi:10.1016/S1381-1169(01)00436-8.
  7. ↑ Buchmeiser, Michael R.; Wurst, K. (December 1999). "Access to Well-Defined Heterogeneous Catalytic Systems via Ring-Opening Metathesis Polymerization (ROMP): Applications in Palladium(II)-Mediated Coupling Reactions". Journal of the American Chemical Society. 121 (48): 11101–11107. doi:10.1021/ja991501r. ISSN   0002-7863.
  8. ↑ Davies, Ian W.; Matty, Louis; Hughes, David L.; Reider, Paul J. (October 2001). "Are Heterogeneous Catalysts Precursors to Homogeneous Catalysts?". Journal of the American Chemical Society. 123 (41): 10139–10140. doi:10.1021/ja016877v. ISSN   0002-7863. PMID   11592910.
  9. ↑ Aksın, Özge; Türkmen, Hayati; Artok, Levent; Çetinkaya, Bekir; Ni, Chaoying; Büyükgüngör, Orhan; Özkal, Erhan (June 2006). "Effect of immobilization on catalytic characteristics of saturated Pd-N-heterocyclic carbenes in Mizoroki–Heck reactions". Journal of Organometallic Chemistry. 691 (13): 3027–3036. doi:10.1016/j.jorganchem.2006.03.012. hdl: 11147/2119 .
  10. ↑ Batail, Nelly; Bendjeriou, Anissa; Djakovitch, Laurent; Dufaud, Véronique (November 2010). "Larock indole synthesis using palladium complexes immobilized onto mesoporous silica". Applied Catalysis A: General. 388 (1–2): 179–187. doi:10.1016/j.apcata.2010.08.046.
  11. ↑ Poyatos, Macarena; Márquez, Francisco; Peris, Eduardo; Claver, Carmen; Fernandez, Elena (2003-01-20). "Preparation of a new clay-immobilized highly stable palladium catalyst and its efficient recyclability in the Heck reaction". New Journal of Chemistry. 27 (2): 425–431. doi:10.1039/b204911b.
  12. ↑ Conlon, David A.; Pipik, Brenda; Ferdinand, Simone; LeBlond, Carl R.; Sowa, John R.; Izzo, Bill; Collins, Paul; Ho, Guo-Jie; Williams, J. Michael; Shi, Yao-Jun; Sun, Yongkui (August 2003). "Suzuki–Miyaura Cross-Coupling With Quasi-Heterogeneous Palladium". Advanced Synthesis & Catalysis. 345 (8): 931–935. doi:10.1002/adsc.200303036. ISSN   1615-4150.
  13. ↑ MacQuarrie, Stephanie; Horton, J. Hugh; Barnes, Jack; McEleney, Kevin; Loock, Hans-Peter; Crudden, Cathleen M. (2008-04-14). "Visual Observation of Redistribution and Dissolution of Palladium during the Suzuki–Miyaura Reaction". Angewandte Chemie International Edition. 47 (17): 3279–3282. doi:10.1002/anie.200800153. hdl: 1974/14138 . PMID   18381727.
  14. ↑ Cantillo, David; Kappe, C. Oliver (December 2014). "Immobilized Transition Metals as Catalysts for Cross-Couplings in Continuous Flow-A Critical Assessment of the Reaction Mechanism and Metal Leaching". ChemCatChem. 6 (12): 3286–3305. doi:10.1002/cctc.201402483. S2CID   97784933.
  15. ↑ Fan, Xiaolei; Manchon, Maria Gonzalez; Wilson, Karen; Tennison, Steve; Kozynchenko, Alexander; Lapkin, Alexei A.; Plucinski, Pawel K. (2009-10-25). "Coupling of Heck and hydrogenation reactions in a continuous compact reactor". Journal of Catalysis. 267 (2): 114–120. doi:10.1016/j.jcat.2009.07.019.
  16. ↑ Gallezot, Pierre (2003). "Hydrogenation - Heterogeneous" in Encyclopedia of Catalysis. John Wiley & Sons.
  17. ↑ Ceylan, Sascha; Friese, Carsten; Lammel, Christian; Mazac, Karel; Kirschning, Andreas (2008-11-03). "Inductive Heating for Organic Synthesis by Using Functionalized Magnetic Nanoparticles Inside Microreactors". Angewandte Chemie International Edition. 47 (46): 8950–8953. doi: 10.1002/anie.200801474 . PMID   18924199.
  18. ↑ Panda, Niranjan; Jena, Ashis Kumar; Mohapatra, Sasmita; Rout, Smruti Ranjan (April 2011). "Copper ferrite nanoparticle-mediated N-arylation of heterocycles: a ligand-free reaction". Tetrahedron Letters. 52 (16): 1924–1927. doi:10.1016/j.tetlet.2011.02.050.
  19. 1 2 Roy, David; Uozumi, Yasuhiro (2018-02-15). "Recent Advances in Palladium-Catalyzed Cross-Coupling Reactions at ppm to ppb Molar Catalyst Loadings". Advanced Synthesis & Catalysis. 360 (4): 602–625. doi: 10.1002/adsc.201700810 .
  20. ↑ Farina, Vittorio (December 2004). "High-Turnover Palladium Catalysts in Cross-Coupling and Heck Chemistry: A Critical Overview". Advanced Synthesis & Catalysis. 346 (13–15): 1553–1582. doi:10.1002/adsc.200404178.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.