James Sanderson

Gold catalysis has recently found its first large-scale applications in the chemical industry. This Minireview provides a critical analysis of the success factors and of the main obstacles that had to be overcome on the long way from the discovery to the commercialization of gold catalysts. The insights should be useful to researchers in both academia and industry working on the development of tomorrow's gold catalysts to tackle significant environmental and economic issues.

Golden future: Gold catalysis has recently found large-scale applications in industry. This Minireview analyzes the success factors and main obstacles that had to be overcome on the long way from discovery of gold catalysts to commercialization. The picture shows a carbide-based PVC plant in China for the gold-catalyzed hydrochlorination of acetylene. (We thank the United Nations Environment Programme and its Global Mercury Partnership for providing the picture.)

A Pd complex, cis-[Pd(C₆F₅)₂(THF)₂] (1), is proposed as a useful touchstone for direct and simple experimental measurement of the relative ability of ancillary ligands to induce C−C coupling. Interestingly, 1 is also a good alternative to other precatalysts used to produce Pd⁰L. Complex 1 ranks the coupling ability of some popular ligands in the order P^tBu₃>o-TolPEWO-F≈tBuXPhos>P(C₆F₅)₃≈PhPEWO-F>P(o-Tol)₃≈THF≈tBuBrettPhos≫Xantphos≈PhPEWO-H≫PPh₃ according to their initial coupling rates, whereas their efficiency, depending on competitive hydrolysis, is ranked tBuXPhos≈P^tBu₃≈o-TolPEWO-F>PhPEWO-F>P(C₆F₅)₃≫tBuBrettPhos>THF≈P(o-Tol)₃>Xantphos>PhPEWO-H≫PPh₃. This “meter” also detects some other possible virtues or complications of ligands such as tBuXPhos or tBuBrettPhos.

Squeezing cross-coupling products: Complex cis-[Pd(C₆F₅)₂(THF)₂] was used as a meter to quantify directly the efficiency of ligands to promote reductive elimination in carbon–carbon bond formation. The ligand could be ranked and compared to others. The complex is a good precatalyst for palladium(0) catalytic species PdL_n.

Since its original discovery over a century ago, the water-gas shift reaction (WGSR) has played a crucial role in industrial chemistry, providing a source of H₂ to feed fundamental industrial transformations such as the Haber–Bosch synthesis of ammonia. Although the production of hydrogen remains nowadays the major application of the WGSR, the advent of homogeneous catalysis in the 1970s marked the beginning of a synergy between WGSR and organic chemistry. Thus, the reducing power provided by the CO/H₂O couple has been exploited in the synthesis of fine chemicals; not only hydrogenation-type reactions, but also catalytic processes that require a reductive step for the turnover of the catalytic cycle. Despite the potential and unique features of the WGSR, its applications in organic synthesis remain largely underdeveloped. The topic will be critically reviewed herein, with the expectation that an increased awareness may stimulate new, creative work in the area.

New directions for a classic: In addition to its fundamental role in the production of hydrogen, the water-gas shift reaction has found application in a multitude of reductive transformations in organic synthesis. These include hydrogenation-type reactions, as well as catalytic, overall-reductive processes wherein the CO/H₂O couple can act as the terminal reductant.

The highly enantioselective hydrogenation of linear enones catalyzed by Ir complexes that bear a chiral P,N ligand have been investigated computationally. Compared to the results of previous studies, the mechanism is different because of the coordination of the substrate. In the favored pathway Ir stays in the +3 oxidation state throughout the entire catalytic cycle, the olefinic group is coordinated trans to the ligand N atom, and the carbonyl group binds trans to a spectator hydride. After migratory insertion, a H₂ coordinates and delivers the second H atom by σ-metathesis. The calculated path rationalizes the observed enantioselectivities and allows the development of a predictive quadrant model for this class of substrate–ligand combination.

Which pathway? Highly enantioselective hydrogenations of linear enones catalyzed by Ir complexes that bear a chiral P,N ligand are investigated computationally. Compared to the results of previous studies, the mechanism is different because of the coordination of the substrate. The calculated path rationalizes the observed enantioselectivities and allows the development a predictive quadrant model for this class of substrate–ligand combination.

Iron-catalyzed cross-coupling reactions have an outstanding potential for sustainable organic synthesis, but remain poorly understood mechanistically. Here, we use electrospray-ionization (ESI) mass spectrometry to identify the ionic species formed in these reactions and characterize their reactivity. Transmetalation of Fe(acac)₃ (acac=acetylacetonato) with PhMgCl in THF (tetrahydrofuran) produces anionic iron ate complexes, whose nuclearity (1 to 4 Fe centers) and oxidation states (ranging from −I to +III) crucially depend on the presence of additives or ligands. Upon addition of iPrCl, formation of the heteroleptic Fe^III complex [Ph₃Fe(iPr)]⁻ is observed. Gas-phase fragmentation of this complex results in reductive elimination and release of the cross-coupling product with high selectivity.

Iron up close and personal: Analysis of iron-catalyzed cross-coupling reactions by electrospray-ionization mass spectrometry finds a multitude of anionic organoferrate complexes covering a remarkable range of different oxidation states. Gas-phase fragmentation experiments afford in-depth insight into the reactivity of these elusive species.

Environmental profiles for the selected metals were compiled on the basis of available data on their biological activities. Analysis of the profiles suggests that the concept of toxic heavy metals and safe nontoxic alternatives based on lighter metals should be re-evaluated. Comparison of the toxicological data indicates that palladium, platinum, and gold compounds, often considered heavy and toxic, may in fact be not so dangerous, whereas complexes of nickel and copper, typically assumed to be green and sustainable alternatives, may possess significant toxicities, which is also greatly affected by the solubility in water and biological fluids. It appears that the development of new catalysts and novel applications should not rely on the existing assumptions concerning toxicity/nontoxicity. Overall, the available experimental data seem insufficient for accurate evaluation of biological activity of these metals and its modulation by the ligands. Without dedicated experimental measurements for particular metal/ligand frameworks, toxicity should not be used as a “selling point” when describing new catalysts.

Heavy weights versus the light weights: A comparison of available data on biological activity of metals commonly used in catalysis suggests that the assumption of toxic heavy metals and benign lighter metals should be re-evaluated. The available experimental data are insufficient for accurate evaluation of biological activity of these metals. Therefore, without dedicated experimental measurements, toxicity should not be used as a “selling point” when describing new catalysts.

Exploiting catalytic carbonyl–olefin metathesis is an ongoing challenge in organic synthesis. Reported herein is an FeCl₃-catalyzed ring-closing carbonyl–olefin metathesis. The protocol allows access to a range of carbo-/heterocyclic alkenes with good efficiency and excellent trans diastereoselectivity. The methodology presents one of the rare examples of catalytic ring-closing carbonyl–olefin metathesis. This process is proposed to take place by FeCl₃-catalyzed oxetane formation followed by retro-ring-opening to deliver metathesis products.

Ironing it out: The title reaction allows access to a range of carbo-/heterocyclic alkenes. The reaction is proposed to take place by FeCl₃-catalyzed oxetane formation followed by retro-ring-opening to deliver the metathesis products.

The reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords enantiomerically pure diarylalkanes in up to 98 % yield and greater than 99.5 % enantiomeric excess. This ligand coupling reaction is tolerant to multiple substitution patterns and provides access to diverse areas of chemical space in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron-deficient heteroaromatic compounds, which are traditionally synthesized by transition metal catalyzed cross-couplings, and circumvents common issues associated with proto-demetalation and β-hydride elimination.

On three: The reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords diarylalkanes with greater than 99.5 % enantiomeric excess. The reaction is tolerant to multiple substitution patterns and proceeds in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron-deficient heteroaromatic compounds.