Jose R. Cabrero-Antonino

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.

Synthesis and Stabilization of Subnanometric Gold Oxide Nanoparticles on Multiwalled Carbon Nanotubes and Their Catalytic Activity

Small gold nanoclusters in a very narrow size distribution (1.1 ± 0.5 nm) have been stabilized onto multiwalled carbon nanotubes (MWCNT). Theoretical studies supported by XPS and (16)O(2)/(18)O(2) isotopic exchange experiments have shown that, on small gold nanoparticles (0.9-1.5 nm), dissociation of molecular O(2) and formation of a surface oxide-like layer is energetically favorable and occurs at room temperature, while O(2) recombination and desorption involves a larger activation barrier. CO titration experiments and theoretical studies demonstrate that the reactivity of the oxidized particles toward CO does not only depend on particle size but also on oxygen coverage. The oxidation-reduction process described is reversible, and the oxidized nanoparticles are active in the epoxidation of styrene with air.

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.

A General and Highly Selective Cobalt‐Catalyzed Hydrogenation of N‐Heteroarenes under Mild Reaction Conditions

Herein, a general and efficient method for the homogeneous cobalt-catalyzed hydrogenation of N-heterocycles, under mild reaction conditions, is reported. Key to success is the use of the tetradentate ligand tris(2-(diphenylphosphino)phenyl)phosphine). This non-noble metal catalyst system allows the selective hydrogenation of heteroarenes in the presence of a broad range of other sensitive reducible groups.

Iron(III) Triflimide as a Catalytic Substitute for Gold(I) in Hydroaddition Reactions to Unsaturated Carbon–Carbon Bonds

In this work it is shown that iron(III) and gold(I) triflimide efficiently catalyze the hydroaddition of a wide array of nucleophiles including water, alcohols, thiols, amines, alkynes, and alkenes to multiple C-C bonds. The study of the catalytic activity and selectivity of iron(III), gold(I), and Brønsted triflimides has unveiled that iron(III) triflimide [Fe(NTf2)3] is a robust catalyst under heating conditions, whereas gold(I) triflimide, even stabilized by PPh3, readily decomposes at 80 °C and releases triflimidic acid (HNTf2) that can catalyze the corresponding reaction, as shown by in situ (19)F, (15)N, and (31)P NMR spectroscopy. The results presented here demonstrate that each of the two catalyst types has weaknesses and strengths and complement each other. Iron(III) triflimide can act as a substitute of gold(I) triflimide as a catalyst for hydroaddition reactions to unsaturated carbon-carbon bonds.

A general protocol for the reductive N-methylation of amines using dimethyl carbonate and molecular hydrogen: mechanistic insights and kinetic studies

Herein, we report for the first time a general and selective ruthenium-catalyzed reductive methylation of amines using dimethyl carbonate as a C1 source and molecular hydrogen as a reducing agent. Notably, this methodology allows N-methylated tertiary aromatic and aliphatic amines to be obtained with good to excellent yields using a green, non-toxic and biodegradable carbon source in the presence of an in situ formed Ru/Triphos complex. The catalytic protocol presented here opens the possibility of developing new sustainable processes for the selective synthesis of N-methyl substituted amines using molecular hydrogen. Mechanistic and kinetic studies have been carried out in order to understand the pathways involved in the general reaction mechanism for the N-methylation of aniline.

Beyond Acid Strength in Zeolites: Soft Framework Counteranions for Stabilization of Carbocations on Zeolites and Its Implication in Organic Synthesis

The generation of a carbocation with an acid depends not only on the acid strength but also on the ability of the counteranion to stabilize the positive charge left behind. Here we report that despite their relatively weak acidity, zeolites are able to generate and stabilize medium-size (molecular weight ≈300 Da) delocalized carbocations on their surface under mild reaction conditions, as it can be done by strong Brønsted or Lewis acids in solution. The zeolite thus acts as a soft macroanion, prolonging the lifetime of the carbocation sufficiently to perform multifunctionalization reactions with amides, thioamides, and phenols, with high yield and selectivity. Biological studies show that some of the products obtained here present significant inhibition activity against colon cancer cells, illustrating the new possibilities of zeolites to prepare complex organic molecules.

Selective Hydrogenation of Nitriles to Primary Amines by using a Cobalt Phosphine Catalyst

A general procedure for the catalytic hydrogenation of nitriles to primary amines by using a non-noble metal-based system is presented. Co(acac)3 in combination with tris[2-(dicyclohexylphosphino)ethyl]phosphine efficiently catalyzes the selective hydrogenation of a wide range of (hetero)aromatic and aliphatic nitriles to give the corresponding amines.

Selective Ruthenium‐Catalyzed Reductive Alkoxylation and Amination of Cyclic Imides

Reported herein, for the first time, is the selective ruthenium-catalyzed reductive alkoxylation and amination of phthalimides/succinimides. Notably, this novel methodology avoids hydrogenation of the aromatic ring and allows methoxylation of substituted imides with good to excellent selectivity for one of the carbonyl groups. The reported method opens the door to the development of new processes for the selective synthesis of various functionalized N-heterocyclic compounds. As an example, intramolecular reductive couplings to afford tricyclic compounds are presented for the first time.

Esters, Including Triglycerides, and Hydrogen as Feedstocks for the Ruthenium-Catalyzed Direct N-Alkylation of Amines.

Triglycerides are used for the direct N-alkylation of amines with molecular hydrogen for the first time. A broad range of interesting and industrially relevant secondary and tertiary amines are obtained in the presence of an in situ formed Ru/Triphos complex. Notably, plant oil can be efficiently applied in this single-step process. Moreover, a variety of other methyl esters can be used as N-alkylation agents in the presence of hydrogen for the synthesis of more advanced building blocks.