Project description:A protocol has been developed that not only simplifies the preparation of nanoparticles (NPs) containing ppm levels of ligated palladium that affect heterogeneous catalysis but also ensures that they afford products of cross-couplings reproducibly due to the freshly prepared nature of each reagent. Four different types of couplings are studied: Suzuki-Miyaura, Sonogashira, Mizoroki-Heck, and Negishi reactions, all performed under mild aqueous micellar conditions. The simplified process relies on the initial formation of stable, storable Pd- and ligand-free NPs, to which is then added the appropriate amount of Pd(OAc)2 and ligand-matched to the desired type of coupling, in water.
Project description:A 1 : 1 Pd : ligand complex, [t-BuXPhos(Pd-π-cinnamyl)]OTf, has been identified as a highly robust pre-catalyst for amination reactions leading to diarylamines, where loadings of metal are typically at 1000 ppm Pd, run in water at temperatures between rt and 45 °C. The protocol is exceptionally simple, is readily scaled, and compares very favorably vs. traditional amination conditions. It has also been shown to successfully lead to key intermediates associated with several physiologically active compounds.
Project description:A new catalyst that derives from commercially available precursors for copper-free, Pd-catalyzed Sonogashira reactions at the sustainable ppm level of precious metal palladium under mild aqueous micellar conditions has been developed. Both the palladium pre-catalyst and ligand are commercially available, bench stable, and highly cost-effective. The catalyst is applicable to both aryl- and heteroaryl-bromides as educts. A wide range of functional groups are tolerated and the aqueous reaction medium can be recycled. An application to a key intermediate associated with an active pharmaceutical ingredient (ponatinib) is discussed.
Project description:A newly engineered palladacycle that contains substituents on the biphenyl rings along with the ligand HandaPhos is especially well-matched to an aqueous micellar medium, enabling valued Suzuki-Miyaura couplings to be run not only in water under mild conditions, but at 300 ppm of Pd catalyst. This general methodology has been applied to several targets in the pharmaceutical area. Multiple recyclings of the aqueous reaction mixture involving both the same as well as different coupling partners is demonstrated. Low temperature microscopy (cryo-TEM) indicates the nature and size of the particles acting as nanoreactors. Importantly, given the low loadings of Pd invested per reaction, ICP-MS analyses of residual palladium in the products shows levels to be expected that are well within FDA allowable limits.
Project description:The palladium-catalyzed enantioselective allylic substitution by carbon or nitrogen nucleophiles is a key transformation that is particularly useful for the synthesis of bioactive compounds. Unfortunately, the selection of a suitable ligand/substrate combination often requires significant screening effort. Here, we show that a transition state force field (TSFF) derived by the quantum-guided molecular mechanics (Q2MM) method can be used to rapidly screen ligand/substrate combinations. Testing of this method on 77 literature reactions revealed several cases where the computationally predicted major enantiomer differed from the one reported. Interestingly, experimental follow-up led to a reassignment of the experimentally observed configuration. This result demonstrates the power of mechanistically based methods to predict and, where necessary, correct the stereochemical outcome.
Project description:Several ppm level gold-catalyzed reactions enabled by the ligand HandaPhos can be performed at room temperature in aqueous nanoreactors composed of the surfactant Nok. Variously substituted allenes undergo cycloisomerization leading to heterocyclic products in good yields. Likewise, cyclodehydration is also illustrated under similar conditions, as is an intermolecular variant, hydration of terminal alkynes. Recycling of the catalyst and reaction medium is also illustrated. A low E factor associated with limited solvent use and therefore, waste generation, documents the greenness of this process.
Project description:A new biaryl phosphine-containing ligand from an active palladium catalyst for ppm level Suzuki-Miyaura couplings, enabled by an aqueous micellar reaction medium. A wide array of functionalized substrates including aryl/heteroaryl bromides are amenable, as are, notably, chlorides. The catalytic system is both general and highly effective at low palladium loadings (1000-2500 ppm or 0.10-0.25 mol%). Density functional theory calculations suggest that greater steric congestion in N2Phos induces increased steric crowding around the Pd center, helping to destabilize the 2 : 1 ligand-Pd(0) complex more for N2Phos than for EvanPhos (and less bulky ligands), and thereby favoring formation of the 1 : 1 ligand-Pdo complex that is more reactive in oxidative addition to aryl chlorides.
Project description:Herein, we describe the use of Pd nanoparticles immobilized on an amino-functionalized siliceous mesocellular foam for the catalytic oxidation of H2O. The Pd nanocatalyst proved to be capable of mediating the four-electron oxidation of H2O to O2, both chemically and photochemically. The Pd nanocatalyst is easy to prepare and shows high chemical stability, low leaching, and recyclability. Together with its promising catalytic activity, these features make the Pd nanocatalyst of potential interest for future sustainable solar-fuel production.
Project description:This Review examines parts per million (ppm) palladium concentrations in catalytic cross-coupling reactions and their relationship with mole percentage (mol %). Most studies in catalytic cross-coupling chemistry have historically focused on the concentration ratio between (pre)catalyst and the limiting reagent (substrate), expressed as mol %. Several recent papers have outlined the use of "ppm level" palladium as an alternative means of describing catalytic cross-coupling reaction systems. This led us to delve deeper into the literature to assess whether "ppm level" palladium is a practically useful descriptor of catalyst quantities in palladium-catalyzed cross-coupling reactions. Indeed, we conjectured that many reactions could, unknowingly, have employed low "ppm levels" of palladium (pre)catalyst, and generally, what would the spread of ppm palladium look like across a selection of studies reported across the vast array of the cross-coupling chemistry literature. In a few selected examples, we have examined other metal catalyst systems for comparison with palladium.
Project description:This report describes a two-phase synthesis of water-soluble carboxylate-functionalized alkanethiolate-capped Pd nanoparticles from ω-carboxyl-S-alkanethiosulfate sodium salts. The two-phase methodology using the thiosulfate ligand passivation protocol allowed a highly specific control over the surface ligand coverage of these nanoparticles, which are lost in a one-phase aqueous system because of the base-catalyzed hydrolysis of thiosulfate to thiolate. Systematic synthetic variations investigated in this study included the concentration of ω-carboxyl-S-alkanethiosulfate ligand precursors and reducing agent, NaBH4, and the overall ligand chain length. The resulting water-soluble Pd nanoparticles were isolated and characterized by transmission electron microscopy (TEM), thermogravimetric analysis (TGA), (1)H NMR, UV-vis, and FT-IR spectroscopy. Among different variations, a decrease in the molar equivalent of NaBH4 resulted in a reduction in the surface ligand density while maintaining a similar particle core size. Additionally, reducing the chain length of the thiosulfate ligand precursor also led to the formation of stable nanoparticles with a lower surface coverage. Since the metal core size of these Pd nanoparticle variations remained quite consistent, direct correlation studies between ligand properties and catalytic activities against hydrogenation/isomerization of allyl alcohol could be performed. Briefly, Pd nanoparticles dissolved in water favored the hydrogenation of allyl alcohol to 1-propanol whereas Pd nanoparticles heterogeneously dispersed in chloroform exhibited a rather high selectivity towards the isomerization product (propanal). The results suggested that the surrounding ligand environments, such as the ligand structure, conformation, and surface coverage, were crucial in determining the overall activity and selectivity of the Pd nanoparticle catalysts.