Intriguing mechanistic labyrinths in gold(<scp>i</scp>) catalysis

Obradors, Carla; Echavarren, Antonio M.

doi:10.1039/c3cc45518a

Cited by 311 publications

(115 citation statements)

References 244 publications

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“…[21][22][23][24][25][26] We have chosen 1-phenylpropyne as a model alkyne and [AuCl(PPh 3 )] and [AuCl(IPr)] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) as representative catalysts. It has been shown that with a gold catalyst bearing a small ligand such as trimethylphosphine or triphenylphospine the reaction proceeds via the formation of geminally diaurated complexes, which are subsequently protodeaurated to form the product of the reaction.…”

Section: Introductionmentioning

confidence: 99%

Reaction Intermediates Kinetics in Solution Investigated by Electrospray Ionization Mass Spectrometry: Diaurated Complexes

et al. 2015

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A new method to investigate the reaction kinetics of intermediates in solution by electrospray ionization mass spectrometry is presented. The method, referred to as delayed reactant labeling, allows investigation of a reaction mixture containing isotopically labeled and unlabeled reactants with different reaction times. It is shown that we can extract rate constants for the degradation of reaction intermediates and investigate the effects of various reaction conditions on their half-life. This method directly addresses the problem of the relevance of detected gaseous ions toward the investigated reaction solution. It is demonstrated for geminally diaurated intermediates formed in the gold mediated addition of methanol to alkynes. Delayed reactant labeling allows us to directly link the kinetics of the diaurated intermediates with the overall reaction kinetics determined by NMR spectroscopy. It is shown that the kinetics of protodeauration of these intermediates mirrors the kinetics of the addition of methanol demonstrating they are directly involved in the catalytic cycle. Formation as well as decomposition of diaurated intermediates can be drastically slowed down by employing bulky ancillary ligands at the gold catalyst; the catalytic cycle then proceeds via monoaurated intermediates. The reaction is investigated for 1-phenylpropyne (Ph-CC-CH3) using [AuCl(PPh3)]/AgSbF6 and [AuCl(IPr)]/AgSbF6 as model catalysts. Delayed reactant labeling is achieved by using a combination of CH3OH and CD3OH or Ph-CC-CH3 and Ph-CC-CD3.

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Section: Introductionmentioning

confidence: 99%

Reaction Intermediates Kinetics in Solution Investigated by Electrospray Ionization Mass Spectrometry: Diaurated Complexes

et al. 2015

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“…6 According to the generally accepted mechanism for gold-catalyzed functionalization of unsaturated hydrocarbon compounds (UHC), the first step consists of the coordination of the gold fragment [LAu] + to the UHC. Upon coordination, the substrate becomes electronically depleted and prone to undergo a nucleophilic attack.…”

Section: ■ Introductionmentioning

confidence: 99%

Strong Electron-Donating Ligands Accelerate the Protodeauration Step in Gold(I)-Catalyzed Reactions: A Quantitative Understanding of the Ligand Effect

et al. 2016

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We have conducted a theoretical exploration of the ligand electronic effect in the protodeauration step of a model gold(I) cyclization reaction, for which experimental data are available. The mechanism of the protodeauration is investigated through a density functional theory (DFT) approach, and the electron-donating power of the ligand is quantified through the charge displacement function (CDF). We find that the frequently encountered assumption in the literature that "strong electron-donating ligands accelerate the protodeauration" can be set into a quantitative framework by our combined DFT/CDF theoretical approach, which allows us also to rationalize the highest catalytic efficiency of Buchwald phosphine type ligands in this process. We analyze the ligand effect on the gold complex-substrate (LAu-S) bond strength, namely the bond to be broken during the protodeauration, and we find that the LAu-S interaction energies linearly correlate with the activation barriers. Finally, energy decomposition analysis (EDA) is used to investigate the LAu-S bond, and we show that changes in the interaction energies are mainly due to changes in the electrostatic component, whose value is in turn modulated by the ligand electron-donating power

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“…We hypothesized that the low reactivity of 8a was due to its lower electron density and greater steric hindrance of the alkyne, compared to the alkyne in 5 . Therefore, we evaluated catalysts with higher electrophilicity, [37] as well as platinum catalysts, which have been utilized in efficient carbocyclizations of 1,6-enynes. [38, 39] However in our system, the majority of the substrate decomposed with all platinum catalysts tested (entries 3-5).…”

Section: Resultsmentioning

confidence: 99%

“…It was also suggested that aurophillic bonded intermediates were involved in gold-catalyzed transformations. [37,41] These may lead to undesired reaction pathways, resulting in low yield of the desired product. [40] Hence, we decided to screen additional phosphine ligands.…”

Section: Resultsmentioning

confidence: 99%

Property‐Guided Synthesis of Aza‐Tricyclic Indolines: Development of Gold Catalysis En Route

et al. 2016

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Antibiotic resistance is a worldwide public health threat that needs to be addressed by improved antibiotic stewardship and continuing development of new chemical entities to treat resistant bacterial infections. Compounds that work alongside known antibiotics as combination therapies offer an efficient and sustainable approach to counteract antibiotic resistance in bacteria. Guided by property-based analysis, a series of aza-tricyclic indolines (ATIs) were synthesized to optimize their physiochemical properties as novel combination therapies with β-lactams to treat methicillin-resistant S. aureus (MRSA) infections. A novel and highly efficient gold-catalyzed tandem cyclization was developed to facilitate the synthesis of these ATIs. One guanidine-containing ATI was discovered to possess both improved anti-MRSA activity and lower mammalian toxicity both in vitro and in vivo. In addition, it also showed significantly enhanced aqueous solubility and metabolic stability. These results indicated that the ATIs are a novel class of anti-MRSA agents suitable for further evaluations as adjuvant therapy in animal model studies.

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Intriguing mechanistic labyrinths in gold(i) catalysis

Abstract: Gold(i) controls complex transformations proceeding through carbocationic species by stabilising the key reactive intermediates.

Cited by 311 publications

References 244 publications

Reaction Intermediates Kinetics in Solution Investigated by Electrospray Ionization Mass Spectrometry: Diaurated Complexes

Reaction Intermediates Kinetics in Solution Investigated by Electrospray Ionization Mass Spectrometry: Diaurated Complexes

Strong Electron-Donating Ligands Accelerate the Protodeauration Step in Gold(I)-Catalyzed Reactions: A Quantitative Understanding of the Ligand Effect

Property‐Guided Synthesis of Aza‐Tricyclic Indolines: Development of Gold Catalysis En Route

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