Multi-Catalytic Metal-Based Homogeneous-Heterogeneous Systems in Organic Chemistry.

The combination of metal-based homogeneous and heterogeneous catalysts in the same reaction media is a powerful, yet relatively unexplored approach in organic chemistry. This strategy can address important limitations associated with purely homogeneous or heterogeneous catalysis such as the incompatibility of different catalytic species in solution, or the limited tunability of solid catalysts, respectively. Moreover, the facile reusability of the solid catalyst, contributes to increase the overall sustainability of the process. As a result, this semi-heterogeneous multi-catalytic approach has unlocked significant advances in organic chemistry, improving existing reactions and even enabling the discovery of novel transformations, exemplified by the formal alkane metathesis. This concept article aims to showcase the benefits of this strategy through exploration of diverse relevant examples from the literature, hoping to spur research on new metal-based homogeneous-heterogeneous catalyst combinations that will result in reactivity challenging to achieve by conventional homogeneous or heterogeneous catalysis alone.

Mechanistic Investigation of the Rhodium-Catalyzed Transfer Hydroarylation Reaction Involving Reversible C-C Bond Activation.

Carbon-carbon (C-C) bonds are ubiquitous but are among the least reactive bonds in organic chemistry. Recently, catalytic approaches to activate C-C bonds by transition metals have demonstrated the synthetic potential of directly reorganizing the skeleton of small molecules. However, these approaches are usually restricted to strained molecules or rely on directing groups, limiting their broader impact. We report a detailed mechanistic study of a rare example of catalytic C-C bond cleavage of unstrained alcohols that enables reversible ketone transfer hydroarylation under Rh-catalysis. Combined insight from kinetic analysis, in situ nuclear magnetic resonance (NMR) monitoring, and density functional theory (DFT) calculations supports a symmetric catalytic cycle, including a key reversible ß-carbon elimination event. In addition, we provide evidence regarding the turnover-limiting step, the catalyst resting state, and the role of the sterically encumbered NHC ligand. The study further led to an improved catalytic system with the discovery of two air-stable precatalysts that showed higher activity for the transformation in comparison to the original conditions.

Mechanistic Investigation of the Nickel-Catalyzed Metathesis between Aryl Thioethers and Aryl Nitriles.

Functional group metathesis is an emerging field in organic chemistry with promising synthetic applications. However, no complete mechanistic studies of these reactions have been reported to date, particularly regarding the nature of the key functional group transfer mechanism. Unraveling the mechanism of these transformations would not only allow for their further improvement but would also lead to the design of novel reactions. Herein, we describe our detailed mechanistic studies of the nickel-catalyzed functional group metathesis reaction between aryl methyl sulfides and aryl nitriles, combining experimental and computational results. These studies did not support a mechanism proceeding through reversible migratory insertion of the nitrile into a Ni-Ar bond and provided strong support for an alternative mechanism involving a key transmetalation step between two independently generated oxidative addition complexes. Extensive kinetic analysis, including rate law determination and Eyring analysis, indicated the oxidative addition complex of aryl nitrile as the resting state of the catalytic reaction. Depending on the concentration of aryl methyl sulfide, either the reductive elimination of aryl nitrile or the oxidative addition into the C(sp2)-S bond of aryl methyl sulfide is the turnover-limiting step of the reaction. NMR studies, including an unusual 31P-2H HMBC experiment using deuterium-labeled complexes, unambiguously demonstrated that the sulfide and cyanide groups exchange during the transmetalation step, rather than the two aryl moieties. In addition, Eyring and Hammett analyses of the transmetalation between two Ni(II) complexes revealed that this central step proceeds via an associative mechanism. Organometallic studies involving the synthesis, isolation, and characterization of all putative intermediates and possible deactivation complexes have further shed light on the reaction mechanism, including the identification of a key deactivation pathway, which has led to an improved catalytic protocol.

Activity-Based Approach for Selective Molecular CO2 Sensing.

Carbon dioxide (CO2) impacts every aspect of life, and numerous sensing technologies have been established to detect and monitor this ubiquitous molecule. However, its selective sensing at the molecular level remains an unmet challenge, despite the tremendous potential of such an approach for understanding this molecule's role in complex environments. In this work, we introduce a unique class of selective fluorescent carbon dioxide molecular sensors (CarboSen) that addresses these existing challenges through an activity-based approach. Besides the design, synthesis, and evaluation of these small molecules as CO2 sensors, we demonstrate their utility by tailoring their reactivity and optical properties, allowing their use in a broad spectrum of multidisciplinary applications, including atmospheric sensing, chemical reaction monitoring, enzymology, and live-cell imaging. Collectively, these results showcase the potential of CarboSen sensors as broadly applicable tools to monitor and visualize carbon dioxide across multiple disciplines.

Preparation of Recyclable and Versatile Porous Poly(aryl thioether)s by Reversible Pd-Catalyzed C-S/C-S Metathesis.

Porous organic materials (polymers and COFs) have shown a number of promising properties; however, the lability of their linkages often limits their robustness and can hamper downstream industrial application. Inspired by the outstanding chemical, mechanical, and thermal resistance of the 1D polymer poly(phenylene sulfide) (PPS), we have designed a new family of porous poly(aryl thioether)s, synthesized via a mild Pd-catalyzed C-S/C-S metathesis-based method, that merges the attractive features common to porous polymers and PPS in a single material. In addition, the method is highly modular, allowing to easily introduce application-oriented functionalities in the materials for a series of environmentally relevant applications including metal capture, metal sensing, and heterogeneous catalysis. Moreover, despite their extreme chemical resistance, the polymers can be easily recycled to recover the original monomers, offering an attractive perspective for their sustainable use. In a broader context, these results clearly demonstrate the untapped potential of emerging single-bond metathesis reactions in the preparation of new, recyclable materials.

Acid Catalysis with Alkane/Water Microdroplets in Ionic Liquids.

Ionic liquids are composed of an organic cation and a highly delocalized perfluorinated anion, which remain tight to each other and neutral across the extended liquid framework. Here we show that n-alkanes in millimolar amounts enable a sufficient ion charge separation to release the innate acidity of the ionic liquid and catalyze the industrially relevant alkylation of phenol, after generating homogeneous, self-stabilized, and surfactant-free microdroplets (1-5 µm). This extremely mild and simple protocol circumvents any external additive or potential ionic liquid degradation and can be extended to water, which spontaneously generates microdroplets (ca. 3 µm) and catalyzes Brönsted rather than Lewis acid reactions. These results open new avenues not only in the use of ionic liquids as acid catalysts/solvents but also in the preparation of surfactant-free, well-defined ionic liquid microemulsions.

Cyclic metal(oid) clusters control platinum-catalysed hydrosilylation reactions: from soluble to zeolite and MOF catalysts.

The Pt-catalysed addition of silanes to functional groups such as alkenes, alkynes, carbonyls and alcohols, i.e. the hydrosilylation reaction, is a fundamental transformation in industrial and academic chemistry, often claimed as the most important application of Pt catalysts in solution. However, the exact nature of the Pt active species and its mechanism of action is not well understood yet, particularly regarding regioselectivity. Here, experimental and computational studies together with an ad hoc graphical method show that the hydroaddition of alkynes proceeds through Pt-Si-H clusters of 3-5 atoms (metal(oid) association) in parts per million amounts (ppm), which decrease the energy of the transition state and direct the regioselectivity of the reaction. Based on these findings, new extremely-active (ppm) microporous solid catalysts for the hydrosilylation of alkynes, alkenes and alcohols have been developed, paving the way for more environmentally-benign industrial applications.

Intermolecular Carbonyl-olefin Metathesis with Vinyl Ethers Catalyzed by Homogeneous and Solid Acids in Flow.

The carbonyl-olefin metathesis reaction has experienced significant advances in the last seven years with new catalysts and reaction protocols. However, most of these procedures involve soluble catalysts for intramolecular reactions in batch. Herein, we show that recoverable, inexpensive, easy to handle, non-toxic, and widely available simple solid acids, such as the aluminosilicate montmorillonite, can catalyze the intermolecular carbonyl-olefin metathesis of aromatic ketones and aldehydes with vinyl ethers in-flow, to give alkenes with complete trans stereoselectivity on multi-gram scale and high yields. Experimental and computational data support a mechanism based on a carbocation-induced Grob fragmentation. These results open the way for the industrial implementation of carbonyl-olefin metathesis over solid catalysts in continuous mode, which is still the origin and main application of the parent alkene-alkene cross-metathesis.

Few layer 2D pnictogens catalyze the alkylation of soft nucleophiles with esters.

Group 15 elements in zero oxidation state (P, As, Sb and Bi), also called pnictogens, are rarely used in catalysis due to the difficulties associated in preparing well-structured and stable materials. Here, we report on the synthesis of highly exfoliated, few layer 2D phosphorene and antimonene in zero oxidation state, suspended in an ionic liquid, with the native atoms ready to interact with external reagents while avoiding aerobic or aqueous decomposition pathways, and on their use as efficient catalysts for the alkylation of nucleophiles with esters. The few layer pnictogen material circumvents the extremely harsh reaction conditions associated to previous superacid-catalyzed alkylations, by enabling an alternative mechanism on surface, protected from the water and air by the ionic liquid. These 2D catalysts allow the alkylation of a variety of acid-sensitive organic molecules and giving synthetic relevancy to the use of simple esters as alkylating agents.

Lattice Opening upon Bulk Reductive Covalent Functionalization of Black Phosphorus.

The chemical bulk reductive covalent functionalization of thin-layer black phosphorus (BP) using BP intercalation compounds has been developed. Through effective reductive activation, covalent functionalization of the charged BP by reaction with organic alkyl halides is achieved. Functionalization was extensively demonstrated by means of several spectroscopic techniques and DFT calculations; the products showed higher functionalization degrees than those obtained by neutral routes.

Base-Controlled Heck, Suzuki, and Sonogashira Reactions Catalyzed by Ligand-Free Platinum or Palladium Single Atom and Sub-Nanometer Clusters.

The assumption that oxidative addition is the key step during the cross-coupling reaction of aryl halides has led to the development of a plethora of increasingly complex metal catalysts, thereby obviating in many cases the exact influence of the base, which is a simple, inexpensive, and necessary reagent for this paramount transformation. Here, a combined experimental and computational study shows that the oxidative addition is not the single kinetically relevant step in different cross-coupling reactions catalyzed by sub-nanometer Pt or Pd species, since the reactivity control is shifted toward subtle changes in the base. The exposed metal atoms in the cluster cooperate to enable an extremely easy oxidative addition of the aryl halide, even chlorides, and allow the base to bifurcate the coupling. With sub-nanometer Pd species, amines drive to the Heck reaction, carbonate drives to the Sonogahira reaction, and phosphate drives to the Suzuki reaction, while for Pt clusters and single atoms, good conversion is only achieved using acetate as a base. This base-controlled orthogonal reactivity with ligand-free catalysts opens new avenues in the design of cross-coupling reactions in organic synthesis.

Confined Pt1 1+ Water Clusters in a MOF Catalyze the Low-Temperature Water-Gas Shift Reaction with both CO2 Oxygen Atoms Coming from Water.

The synthesis and reactivity of single metal atoms in a low-valence state bound to just water, rather than to organic ligands or surfaces, is a major experimental challenge. Herein, we show a gram-scale wet synthesis of Pt1 1+ stabilized in a confined space by a crystallographically well-defined first water sphere, and with a second coordination sphere linked to a metal-organic framework (MOF) through electrostatic and H-bonding interactions. The role of the water cluster is not only isolating and stabilizing the Pt atoms, but also regulating the charge of the metal and the adsorption of reactants. This is shown for the low-temperature water-gas shift reaction (WGSR: CO + H2 O → CO2 + H2 ), where both metal coordinated and H-bonded water molecules trigger a double water attack mechanism to CO and give CO2 with both oxygen atoms coming from water. The stabilized Pt1+ single sites allow performing the WGSR at temperatures as low as 50 °C.

Synthesis of Densely Packaged, Ultrasmall Pt02 Clusters within a Thioether-Functionalized MOF: Catalytic Activity in Industrial Reactions at Low Temperature.

The gram-scale synthesis, stabilization, and characterization of well-defined ultrasmall subnanometric catalytic clusters on solids is a challenge. The chemical synthesis and X-ray snapshots of Pt02 clusters, homogenously distributed and densely packaged within the channels of a metal-organic framework, is presented. This hybrid material catalyzes efficiently, and even more importantly from an economic and environmental viewpoint, at low temperature (25 to 140 °C), energetically costly industrial reactions in the gas phase such as HCN production, CO2 methanation, and alkene hydrogenations. These results open the way for the design of precisely defined catalytically active ultrasmall metal clusters in solids for technically easier, cheaper, and dramatically less-dangerous industrial reactions.

Generation and Reactivity of Electron-Rich Carbenes on the Surface of Catalytic Gold Nanoparticles.

The reactive nature of carbenes can be modulated, and ultimately reversed, by receiving additional electron density from a metal. Here, it is shown that Au nanoparticles (NPs) generate an electron-rich carbene on surface after transferring electron density to the carbonyl group of an in situ activated diazoacetate, as assessed by Fourier transformed infrared (FT-IR) spectroscopy, magic angle spinning nuclear magnetic resonance (MAS NMR), and Raman spectroscopy. Density functional theory (DFT) calculations support the observed experimental values and unveil the participation of at least three different Au atoms during carbene stabilization. The surface stabilized carbene shows an extraordinary stability against nucleophiles and reacts with electrophiles to give new products. These findings showcase the ability of catalytic Au NPs to inject electron density in energetically high but symmetrically allowed valence orbitals of sluggish molecules.

A Ligand-Free Pt3 Cluster Catalyzes the Markovnikov Hydrosilylation of Alkynes with up to 106 Turnover Frequencies.

The Pt-catalyzed hydrosilylation of alkynes is the procedure of choice to obtain vinylsilanes, and is claimed to be the most relevant application of Pt in organic synthesis. More than half a century after its discovery, only ß-vinylsilanes (anti-Markovnikov addition) are obtained with simple Pt catalysts, whereas α-vinylsilanes (Markovnikov addition) remain elusive compounds. Here the catalysis of the Markovnikov hydrosilylation of terminal alkynes by Pt3 clusters, in parts-per-million amounts, to give a wide variety of α-vinylsilanes in reasonable isolated yields and with turnover frequencies that can reach up to one million per hour is reported. Moreover, these α-vinylsilanes are reactive in well-stablished C-C bond-forming cascade reactions, in which the corresponding ß-isomers are unreactive. Besides its efficiency and synthetic usefulness, this catalytic system is an excellent example of how the atom-by-atom aggregation of a catalytic metal leads to a different selectivity for a given reaction.

Well-Defined Noble Metal Single Sites in Zeolites as an Alternative to Catalysis by Insoluble Metal Salts.

Insoluble precious metal chlorides in polymeric form (i.e., PtCl2, PdCl2, AuCl, RhCl3) are commonly used as catalysts for a plethora of organic reactions in solution. Here we show that only the minor soluble fraction of these precious metal chlorides (typically 5-30%) is catalytically active for the hydroamination, hydroalkoxylation, hydrosilylation, and cycloisomerization of alkynes and alkenes, and that the resting insoluble metal is catalytically useless. To circumvent this waste of precious metal and follow a rational design, we generate here well-dispersed Pt(II) and Pd(II) single sites on zeolite Y, with an exquisite control of the Lewis acidity, to catalyze different hydroaddition reactions to alkynes and alkenes with up to 10(4) catalytic cycles (at least 2 orders of magnitude superior to precious metal chlorides) and with high isolated yields (82-99%, >15 examples).