Antonio Leyva-Pérez

Gold-Catalyzed Carbon−Heteroatom Bond-Forming Reactions

4.1.2. Intramolecular C-OH Formation 1661 4.1.3. Intermolecular C-OH Formation 1662 4.2. Formation of Ethers 1662 4.2.1. Cyclic Ethers 1662 4.2.2. Acyclic Ethers 1668 4.3. Formation of Acetals 1669 4.3.1. Cyclic Acetals 1670 4.3.2. Acyclic Acetals 1670 4.4. Formation of Aldehydes 1671 4.5. Formation of Ketones 1672 4.5.1. Intramolecular Formation of Ketones 1672 4.5.2. Intermolecular Formation of Ketones 1674 4.6. Formation of Carboxylic Acids 1676 4.7. Formation of Esters 1677 4.7.1. Cyclic Esters 1677 4.7.2. Acyclic Esters 1678 4.8. Formation of Amides 1680 4.9. Formation of Carbonates 1681 4.9.1. Cyclic Carbonates 1681 4.9.2. Acyclic Carbonates 1681 4.10. Formation of Carbamates 1681 4.11. Formation of Sulfonates 1681 4.12. Formation of Phosphonates 1681 4.13. Application of Gold Catalysts in Total Synthesis 1681 4.13.1. Dihydrofurans 1682 4.13.2. Dihydropyranes 1682 4.13.3. Seven-Membered Ether Rings 1682 4.13.4. Acetals 1683 4.13.5. Ketones 1683 4.13.6. Esters 1683 5. Formation of Carbon-Nitrogen Bonds 1684 5.1. Intermolecular C-N Bond Formation 1684 5.1.1. Formation of Amines 1684 5.1.2. Formation of Allylic Amines 1686 5.1.3. Formation of Propargyl Amines 1687 5.1.4. Formation of Enamines and Enamides 1688 5.1.5. Formation of Azides 1688 5.1.6. Formation of Imines 1689 5.2. Intramolecular C-N Bond Formation 1690 5.2.1. Fiveand Six-Membered Rings 1690 5.2.2. Seven-Membered Ring 1698 5.3. Application to Total Synthesis 1699 6. Formation of Carbon-Sulfur Bonds 1699 7. Formation of Carbon-Phosphorus Bonds 1700 7.1. Heterogeneous Catalysis for Formation of Carbon-Phosphorus Bonds 1700

Small Gold Clusters Formed in Solution Give Reaction Turnover Numbers of 107 at Room Temperature

Gold Cluster Catalysis A variety of gold salts and complexes have been used to catalyze different organic reactions. Often, the catalytic rates for these reactions are similar. Oliver-Meseguer et al. (p. 1452; see the Perspective by Hashmi) observed an induction period for the onset of catalysis of organic reactions, such as the ester-assisted hydration of alkynes, for different gold salts and complexes. Mass spectrometry and absorption spectroscopy revealed that small gold clusters (three to ten atoms) formed during these induction periods and are likely to represent the active catalysts. The catalytic reaction rates could be extremely high—up to 105 turnovers of the catalyst per hour. Three- to ten-atom gold clusters formed from gold salts and complexes are highly active catalysts for organic reactions. Very small gold clusters (3 to 10 atoms) formed from conventional gold salts and complexes can catalyze various organic reactions at room temperature, even when present at concentrations of parts per billion. Absorption and emission ultraviolet-visible spectroscopy and matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry revealed that, for example, the ester-assisted hydration of alkynes began only when clusters of three to five gold atoms were formed. The turnover numbers and turnover frequencies associated with these catalyzed reactions can be as high as 107 and 105 per hour, respectively.

Similarities and differences between the "relativistic" triad gold, platinum, and mercury in catalysis.

Relativistic effects in the valence shell of the elements reach a maximum in the triad Pt-Au-Hg and determine their catalytic activity in organic reactions. In this Review we examine the catalytic activity of Pt, Au, and Hg compounds for some representative reactions, and discuss the respective benefits and disadvantages along with other relevant properties, such as toxicity, price, and availability. For the reactions considered, gold catalysts are generally more active than mercury or platinum catalysts.

Theoretical and experimental insights into the origin of the catalytic activity of subnanometric gold clusters: attempts to predict reactivity with clusters and nanoparticles of gold.

Particle size is one of the key parameters determining the unexpected catalytic activity of gold, with reactivity improving as the particle gets smaller. While this is valid in the 1-5 nm range, chemists are now investigating the influence of particle size in the subnanometer regime. This is due to recent advances in both characterization techniques and synthetic routes capable of stabilizing these size-controlled gold clusters. Researchers reported in early studies that small clusters or aggregates of a few atoms can be extremely active in some reactions, while 1-2 nm nanoparticles are catalytically more efficient for other reactions. Furthermore, the possibility that small gold clusters generated in situ from gold salts or complexes could be the real active species in homogeneous gold-catalyzed organic reactions should be considered. In this Account, we address two questions. First, what is the origin of the enhanced reactivity of gold clusters on the subnanometer scale? And second, how can we predict the reactions where small clusters should work better than larger nanoparticles? Both geometric factors and electronic or quantum size effects become important in the subnanometer regime. Geometric reasons play a key role in hydrogenation reactions, where only accessible low coordinated neutral Au atoms are needed to dissociate H2. The quantum size effects of gold clusters are important as well, as clusters formed by only a few atoms have discrete molecule-like electronic states and their chemical reactivity is related to interactions between the clusters frontier molecular orbitals and those of the reactant molecules. From first principles calculations, we predict an enhanced reactivity of small planar clusters for reactions involving activation of CC multiple bonds in alkenes and alkynes through Lewis acid-base interactions, and a better catalytic performance of 3D gold nanoparticles in redox reactions involving bond dissociation by oxidative addition and new bond formation by reductive elimination. In oxidation reactions with molecular O2, initial dissociation of O2 into basic oxygen atoms would be more effectively catalyzed by gold nanoparticles of ∼1 nm diameter. In contrast, small planar clusters should be more active for reactions following a radical pathway involving peroxo or hydroperoxo intermediates. We have experimentally confirmed these predictions for a series of Lewis acid and oxidation reactions catalyzed by gold clusters and nanoparticles either in solution or supported on solid carriers.

MOFs as Multifunctional catalysts: Synthesis of secondary arylamines, quinolines, pyrroles and arylpyrrolidines over bifunctional MIL-101

Bifunctional MIL‐101 MOFs containing Lewis acid Cr3+ sites and Pd or Pt hydrogenation/reduction centers, either as isolated metal complexes or in the form of encapsulated metal nanoparticles, have shown to be highly active catalysts for the one‐pot nitroarene reduction and reductive amination of carbonyl compounds. This preparation procedure has been successfully applied to the synthesis of secondary arylamines, quinolines, pyrrols, and 3‐arylpyrrolidines. In all the cases, the MOFs have shown superior performances with respect to commercially available Pd and Pt metal catalysts under the same conditions.

Water‐Stabilized Three‐ and Four‐Atom Palladium Clusters as Highly Active Catalytic Species in Ligand‐Free CC Cross‐Coupling Reactions

Elite cliques: Palladium clusters with three and four atoms were found to be the catalytically active species for ligand-free palladium-catalyzed CC bond-forming reactions. These palladium cluster species could be stabilized in water and stored for long periods of time for use on demand with no loss of activity. High yields of products and turnover frequencies (TOFs) of up to 10(5)  h(-1) were observed.

Regioselective Hydration of Alkynes by Iron(III) Lewis/Brønsted Catalysis

The triflimide iron(III) salt [Fe(NTf(2))(3)] promotes the direct hydration of terminal and internal alkynes with very good Markovnikov regioselectivities and high yields. The enhanced carbophilic Lewis acidity of the Fe(III) cation mediated by the weakly-coordinating triflimide anion is crucial for the catalytic activity. The iron(III) metal salt can be recycled in the form of the OPPh(3)/[Fe(NTf(2))(3)] system with similar activity and selectivity. However, spectroscopic and kinetic studies show that [Fe(NTf(2))(3)] hydrolyzes under the reaction conditions and that catalytically less active Brønsted species are formed, which points to a Lewis/Brønsted co-catalysis. This triflimide-based catalytic system is regioselective for the hydration of internal aryl-alkynes and opens the door to a new synthetic route to alkyl ketophenones. As a proof of concept, the synthesis of two antipsychotics Haloperidol and Melperone, with general butyrophenone-like structure, is shown.

The MOF-driven synthesis of supported palladium clusters with catalytic activity for carbene-mediated chemistry

The development of catalysts able to assist industrially important chemical processes is a topic of high importance. In view of the catalytic capabilities of small metal clusters, research efforts are being focused on the synthesis of novel catalysts bearing such active sites. Here we report a heterogeneous catalyst consisting of Pd4 clusters with mixed-valence 0/+1 oxidation states, stabilized and homogeneously organized within the walls of a metal-organic framework (MOF). The resulting solid catalyst outperforms state-of-the-art metal catalysts in carbene-mediated reactions of diazoacetates, with high yields (>90%) and turnover numbers (up to 100,000). In addition, the MOF-supported Pd4 clusters retain their catalytic activity in repeated batch and flow reactions (>20 cycles). Our findings demonstrate how this synthetic approach may now instruct the future design of heterogeneous catalysts with advantageous reaction capabilities for other important processes.

Stabilized Naked Sub-nanometric Cu Clusters within a Polymeric Film Catalyze C–N, C–C, C–O, C–S, and C–P Bond-Forming Reactions

Sub-nanometric Cu clusters formed by endogenous reduction of Cu salts and Cu nanoparticles are active and selective catalysts for C-N, C-C, C-O, C-S, and C-P bond-forming reactions. Sub-nanometric Cu clusters have also been generated within a polymeric film and stored with full stability for months. In this way, they are ready to be used on demand and maintain high activity (TONs up to 10(4)) and selectivity for the above reactions. A potential mechanism for the formation of the sub-nanometric clusters and their electronic nature is presented.

Multisite Organic–Inorganic Hybrid Catalysts for the Direct Sustainable Synthesis of GABAergic Drugs

Multisite organic-inorganic hybrid catalysts have been prepared and applied in a new general, practical, and sustainable synthetic procedure toward industrially relevant GABA derivatives. The domino sequence is composed of seven chemical transformations which are performed in two one-pot reactions. The method produces both enantiomeric forms of the product in high enantiopurity as well as the racemate in good yields after a single column purification step. This protocol highlights major process intensification, catalyst recyclability, and low waste generation.