Gold Redox Research Articles

Electrochemical Gold Redox Catalysis

AbstractThe high oxidation potential of Au(I)/Au(III) redox couple renders the development of gold‐catalyzed cross‐coupling reactions highly challenging. In the pursuit of Au(I)/Au(III) redox catalysis, various strategies, such as the use of stoichiometric oxidants, merged gold/photoredox systems, or ligand‐enabled approaches, have been adopted to achieve the oxidation of Au(I) to Au(III) complexes. Recently, electrochemical anodic oxidation‐based gold redox catalysis has emerged as a new technique to facilitate gold‐catalyzed cross‐coupling reactions. This concept article provides a succinct overview of electrochemical gold redox catalysis, highlighting the challenges and potential future developments.

Gold‐Catalyzed Heck and Suzuki‐Type Reactions: Challenges and Recent Advances

AbstractTransition metal‐catalyzed Suzuki and Heck reactions are two of the most common carbon‐carbon bond formation reactions. Gold, unlike other transition metals (Pd, Ni, and Cu), offers unique reactivity profiles, and has emerged as an efficient tool in the field of synthetic organic chemistry. This mini‐review focused on the recent work in gold‐catalyzed Heck and Suzuki‐type reactions, especially by photocatalysts or ligand design, which show reactivities and features distinct from other transition metals. These discoveries will further facilitate the development of gold redox catalysis as well as applications in organic synthesis, biochemistry, and medicinal chemistry.

C(sp2)–CN Cross-Coupling by Ligand-Enabled Gold(I)/Gold(III) Redox Catalysis

C(sp2)–CN Cross-Coupling by Ligand-Enabled Gold(I)/Gold(III) Redox Catalysis

Exploring Ferrocenyl Imine‐Phosphane Complexes in Gold(I) Redox Switchable Catalysis and the Role of the “Magic Blue” Oxidant.

Exploring Ferrocenyl Imine‐Phosphane Complexes in Gold(I) Redox Switchable Catalysis and the Role of the “Magic Blue” Oxidant.

Exploring Ferrocenyl Imine‐Phosphane Complexes in Gold(I) Redox Switchable Catalysis and the Role of the “Magic Blue” Oxidant

AbstractAnother class of gold(I) redox‐switchable catalysts, incorporating ferrocenyl phosphane‐imines, enriches the existing library of gold(I) complexes. Our catalyst proves efficacy in gold(I)‐catalyzed cyclizations of furans and benzamides, exhibiting reversible “on‐off” switching. Furthermore, we explored the unconventional role of “Magic Blue”, commonly used as an oxidizing agent in various organic transformations, as a potential activator of the Au−Cl bond, initiating conventional gold(I) catalysis.

Gold‐Catalyzed Arylative Cope Rearrangement

AbstractCope rearrangements have garnered significant attention owing to their ability to undergo structural reorganization in stereoselective manner. While substantial advances have been achieved over decades, these rearrangements remained applicable exclusively to parent 1,5‐hexadienes. Herein, we disclose the gold‐catalyzed arylative Cope rearrangement of 1,6‐heptadienes via a cyclization‐induced [3,3]‐rearrangement employing ligand‐enabled gold redox catalysis. Detailed mechanistic investigations including several control experiments, cross‐over experiment, HRMS analysis, 31P NMR and DFT studies have been performed to underpin the mechanism.

Gold-Catalyzed Arylative Cope Rearrangement.

Cope rearrangements have garnered significant attention owing to their ability to undergo structural reorganization in stereoselective manner. While substantial advances have been achieved over decades, these rearrangements remained applicable exclusively to parent 1,5-hexadienes. Herein, we disclose the gold-catalyzed arylative Cope rearrangement of 1,6-heptadienes via a cyclization-induced [3,3]-rearrangement employing ligand-enabled gold redox catalysis. Detailed mechanistic investigations including several control experiments, cross-over experiment, HRMS analysis, 31P NMR and DFT studies have been performed to underpin the mechanism.

Consolidation of the Oxidant-Free Au(I)/Au(III) Catalysis Enabled by the Hemilabile Ligand Strategy.

In this minireview we survey the challenges and strategies in gold redox catalysis. Gold's reluctance to oxidative addition reactions due to its high redox potential limits its applicability. Initial attempts to overcome this problem focused on the use of sacrificial external oxidants in stoichiometric amounts to bring Au(I) compounds to Au(III) reactive species. Recently, innovative approaches focused on employing hemilabile ligands, which are capable of coordinating to Au(I) and stabilizing square-planar Au(III) intermediates, thus facilitating oxidative addition steps and enabling oxidant-free catalysis. Notable examples include the use of the (P^N) bidendate MeDalphos ligand to achieve various cross-coupling reactions via oxidative addition Au(I)/Au(III). Importantly, hemilabile ligand-enabled catalysis allows merging oxidative addition with π-activation, such as oxy- and aminoarylation of alkenols and alkenamines using organohalides, expanding gold's versatility in C-C and C-heteroatom bond formations and unprecedented cyclizations. Moreover, recent advancements in enantioselective catalysis using chiral hemilabile (P^N) ligands are also surveyed. Strikingly, versatile bidentate (C^N) hemilabile ligands as competitors of MeDalphos have appeared recently, by designing scaffolds where phosphine groups are substituted by N-heterocyclic or mesoionic carbenes. Overall, these approaches highlight the evolving landscape of gold redox catalysis and its tremendous potential in a broad scope of transformations.

Consolidation of the Oxidant‐Free Au(I)/Au(III) Catalysis Enabled by the Hemilabile Ligand Strategy

AbstractIn this minireview we survey the challenges and strategies in gold redox catalysis. Gold's reluctance to oxidative addition reactions due to its high redox potential limits its applicability. Initial attempts to overcome this problem focused on the use of sacrificial external oxidants in stoichiometric amounts to bring Au(I) compounds to Au(III) reactive species. Recently, innovative approaches focused on employing hemilabile ligands, which are capable of coordinating to Au(I) and stabilizing square‐planar Au(III) intermediates, thus facilitating oxidative addition steps and enabling oxidant‐free catalysis. Notable examples include the use of the (P^N) bidendate MeDalphos ligand to achieve various cross‐coupling reactions via oxidative addition Au(I)/Au(III). Importantly, hemilabile ligand‐enabled catalysis allows merging oxidative addition with π‐activation, such as oxy‐ and aminoarylation of alkenols and alkenamines using organohalides, expanding gold‘s versatility in C−C and C‐heteroatom bond formations and unprecedented cyclizations. Moreover, recent advancements in enantioselective catalysis using chiral hemilabile (P^N) ligands are also surveyed. Strikingly, versatile bidentate (C^N) hemilabile ligands as competitors of MeDalphos have appeared recently, by designing scaffolds where phosphine groups are substituted by N‐heterocyclic or mesoionic carbenes. Overall, these approaches highlight the evolving landscape of gold redox catalysis and its tremendous potential in a broad scope of transformations.

DFT-Enabled Development of Hemilabile (P∧N) Ligands for Gold(I/III) RedOx Catalysis: Application to the Thiotosylation of Aryl Iodides.

Ligand-enabled oxidative addition of Csp2-X bonds to Au(I) centers has recently appeared as a valuable strategy for the development of catalytic RedOx processes. Several cross-coupling reactions that were previously considered difficult to achieve were reported lately, thus expanding the synthetic potential of gold(I) complexes beyond the traditional nucleophilic functionalization of π-systems. MeDalPhos has played an important role in this development and, despite several studies on alternative structures, remains, so far, the only general ligand for such process. We report herein the discovery and DFT-enabled structural optimization of a new family of hemilabile (P∧N) ligands that can promote the oxidative addition of aryl iodides to gold(I). These flexible ligands, which possess a common 2-methylamino heteroaromatic N-donor motif, are structurally and electronically tunable, beyond being easily accessible and affordable. The corresponding Au(I) complexes were shown to outperform the reactivity of (MeDalPhos)Au(I) in a series of alkoxy- and amidoarylations of alkenes. Their synthetic potential and comparatively higher reactivity were further highlighted in the thiotosylation of aryl iodides, a challenging unreported C-S cross-coupling reaction that could not be achieved under classical Pd(0/II) catalysis and that allows for general and divergent access to aryl sulfur derivatives.

Unlocking the catalytic potential of gold(II) complexes: a comprehensive reassessment.

Gold(II) complexes, unlike their gold(I) and gold(III) counterparts, have been sparsely employed in the field of catalysis. This is primarily due to the challenges associated with isolating and characterising these open-shell species. However, these complexes offer a wide range of possibilities. On one hand, this intermediate oxidation state has proven to be more easily accessible through reduction and oxidation processes compared to the gold(I)/gold(III) redox couple, thereby facilitating potential homo-coupling and cross-coupling reactions. On the other hand, gold(II) exhibits Lewis acid behaviour, bridging the characteristics of the soft acid gold(I) and the hard acid gold(III). In this review, we focus on mono- and dinuclear gold(II) complexes, whether they are isolated and well-studied or proposed as intermediates in cross-coupling reactions induced by the action of oxidants or light. We delve into the unique reactivity and potential applications of these gold(II) species, shedding light on their role in this field. This comprehensive exploration aims to underscore the latent promise of gold(II) complexes in catalysis, offering insights into their structural and mechanistic aspects while highlighting their relevance in contemporary chemical transformations.

Accessing gold p-acid reactivity under electrochemical anode oxidation (EAO) through oxidation relay

The gold π-acid activation under electrochemical conditions is achieved. While EAO allows easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far are limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications.

Gold-Manganese Bimetallic Redox Coupling with Light.

The classical Au(I)/Au(III) redox couple chemistry has been limited to constructing C-C and C-X bonds, and thus, the exploration of the elementary reaction of gold redox coupling is very significant to enrich its organometallic features. Herein, we report the first visible-light-mediated, external oxidant-free Au(I)/Au(III) redox couple using commercially available Mn2(CO)10 to generate Mn-Au(III)-Mn intermediates for bimetallic redox coupling. A wide range of structurally diverse heterodinuclear and polynuclear L-Au(I)-Mn-L' complexes (19 examples, up to >99% yields) are readily constructed, providing a robust strategy for the concise construction of Au-Mn complexes under mild reaction conditions. The mechanistic studies together with DFT calculations support the radical oxidative addition of •Mn(CO)5 to gold and bimetallic reductive elimination mechanisms from highly active Mn-Au(III)-Mn species, representing an important step toward an elementary reaction in gold chemistry research. Furthermore, the resulting Au-Mn complexes exhibit unique catalytic activity, with which divergent reductive coupling of nitroarenes can readily afford azoxybenzenes, azobenzenes, and hydrazobenzenes in moderate to good yields.

Advancing Gold Redox Catalysis: Mechanistic Insights, Nucleophilicity-Guided Transmetalation, and Predictive Frameworks for the Oxidation of Aryl Gold(I) Complexes.

Gold redox catalysis, often facilitated by hypervalent iodine(III) reagents, offers unique reactivity but its progress is mainly hindered by an incomplete mechanistic understanding. In this study, we investigated the reaction between the gold(I) complexes [(aryl)Au(PR3 )] and the hypervalent iodine(III) reagent PhICl2 , both experimentally and computationally and provided an explanation for the formation of divergent products as the ligands bonded to the gold(I) center change. We tackled this essential question by uncovering an intriguing transmetalation mechanism that takes place between gold(I) and gold(III) complexes. We found that the ease of transmetalation is governed by the nucleophilicity of the gold(I) complex, [(aryl)Au(PR3 )], with greater nucleophilicity leading to a lower activation energy barrier. Remarkably, transmetalation is mainly controlled by a single orbital - the gold dx 2 -y 2 orbital. This orbital also has a profound influence on the reactivity of the oxidative addition step. In this way, the fundamental mechanistic basis of divergent outcomes in reactions of aryl gold(I) complexes with PhICl2 was established and these observations are reconciled from first principles. The theoretical model developed in this study provides a conceptual framework for anticipating the outcomes of reactions involving [(aryl)Au(PR3 )] with PhICl2 , thereby establishing a solid foundation for further advancements in this field.

Electrochemical Gold‐Catalyzed 1,2‐Difunctionalization of C−C Multiple Bonds**

AbstractHerein, we disclose the first report of 1,2‐difunctionalization of C−C multiple bonds using electrochemical gold redox catalysis. By adopting the electrochemical strategy, the inherent π‐activation and cross‐coupling reactivity of gold catalysis are harnessed to develop the oxy‐alkynylation of allenoates under external‐oxidant‐free conditions. Detailed mechanistic investigations such as 31P NMR, control experiments, mass studies, and cyclic voltammetric (CV) analysis have been performed to support the proposed reaction mechanism.

Unlocking Migratory Insertion in Gold Redox Catalysis

AbstractExploration of elementary reactions in organometallic catalysis is an important method with which to discover new reactions. In this article, we report a gold(I)‐catalyzed iodo‐alkynylation of benzyne involving the merging of challenging migratory insertion and an oxidative addition process in gold catalytic cycle. A wide range of structurally diverse alkynyl iodides are good coupling partners in this iodo‐alkynylation transformation. Both aliphatic and aromatic alkynyl iodides can react with benzynes smoothly to afford highly functionalized 1,2‐disubstituted aromatics in moderate to good yields. Its good functional group compatibility and late‐stage application of complex molecules demonstrate its synthetic robustness. Studies of the mechanism reveals the feasibility of oxidative addition and the DFT calculations demonstrate the possible migratory insertion of benzyne into AuIII‐carbon bonds in the AuI/AuIII redox catalytic cycle, representing an important step towards an elementary reaction in gold chemistry research.

Unlocking Migratory Insertion in Gold Redox Catalysis.

Exploration of elementary reactions in organometallic catalysis is an important method with which to discover new reactions. In this article, we report a gold(I)-catalyzed iodo-alkynylation of benzyne involving the merging of challenging migratory insertion and an oxidative addition process in gold catalytic cycle. A wide range of structurally diverse alkynyl iodides are good coupling partners in this iodo-alkynylation transformation. Both aliphatic and aromatic alkynyl iodides can react with benzynes smoothly to afford highly functionalized 1,2-disubstituted aromatics in moderate to good yields. Its good functional group compatibility and late-stage application of complex molecules demonstrate its synthetic robustness. Studies of the mechanism reveals the feasibility of oxidative addition and the DFT calculations demonstrate the possible migratory insertion of benzyne into AuIII -carbon bonds in the AuI /AuIII redox catalytic cycle, representing an important step towards an elementary reaction in gold chemistry research.

Gold-Catalyzed Aryl-Alkenylation of Alkenes.

Herein, we report the gold-catalyzed aryl-alkenylation of unactivated alkenes with alkenyl iodides and bromides employing ligand-enabled gold redox catalysis. The present methodology followed the π-activation pathway rather than the migratory insertion pathway, which is predominant in other transition metal catalysis such as Pd, Ni, Cu, etc. Detailed mechanistic investigations such as 31P NMR, deuterium labeling, and HRMS studies have been carried out to underpin mechanistic insights.

Gold-catalyzed alkenylation and arylation of phosphorothioates.

Reported herein is the ligand-enabled gold-catalyzed alkenylation and arylation of phosphorothioates using alkenyl and aryl iodides. Mechanistic studies revealed a crucial role of the in situ generated Ag-sulfur complex, which undergoes a facile transmetalation with the Au(iii) intermediate, thereby leading to the successful realization of the present reaction. Moreover, for the first time, the alkenylation of phosphoroselenoates under gold redox catalysis has been presented.

Cover Feature: Chiral Hemilabile P,N‐Ligand‐Assisted Gold Redox Catalysis for Enantioselective Alkene Aminoarylation (Chem. Eur. J. 34/2022)

Enantioselective gold redox catalysis was achieved with newly designed chiral hemilabile P,N ligands (shown as a heavy load in the truck). We reveal a new strategy through a two-step sequence: A) Apply a chiral hemilabile P,N ligand at the AuI stage to promote AuI oxidative addition toward aryl iodide; B) nucleophilic addition to a chiral AuIII intermediate formed in situ as a stereodetermining step (SDS). This strategy presents a new opportunity to enrich the versatile reactivity of gold catalysis in an enantioselective fashion. More information can be found in the Research Article by M. Li, X. Shi and co-workers (DOI: 10.1002/chem.202201018).