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.

Enantioselective merged gold/organocatalysis.

Gold complexes, because of their unique carbophilic nature, have evolved as efficient catalysts for catalyzing various functionalization reactions of C-C multiple bonds. However, the realization of enantioselective transformations via gold catalysis remains challenging due to the geometrical constraints and coordination behaviors of gold complexes. In this context, merged gold/organocatalysis has emerged as one of the intriguing strategies to achieve enantioselective transformations which could not be possible by using a single catalytic system. Historically, in 2009, this field started with the merging of gold with axially chiral Brønsted acids and chiral amines to achieve enantioselective transformations. Since then, based on the unique reactivity profiles offered by each catalyst, several reports utilizing gold in conjunction with various chiral organocatalysts such as amines, Brønsted acids, N-heterocyclic carbenes, hydrogen-bonding and phosphine catalysts have been documented in the literature. This article demonstrates an up-to-date development in this field, especially focusing on the mechanistic interplay of gold catalysts with chiral organocatalysts.

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.

Unlocking the Chain-Walking Process in Gold Catalysis.

The successful realization of gold-catalyzed chain-walking reactions, facilitated by ligand-enabled Au(I)/Au(III) redox catalysis, has been reported for the first time. This breakthrough has led to the development of gold-catalyzed annulation reaction of alkenes with iodoarenes by leveraging the interplay of chain-walking and π-activation reactivity mode. The reaction mechanism has been elucidated through comprehensive experimental and computational studies.

Gold-Catalyzed 1,2-Dicarbofunctionalization of Alkynes with Organohalides.

Herein, we report the first gold-catalyzed 1,2-dicarbofunctionalization of alkynes using organohalides as non-prefunctionalized coupling partners. The mechanism of the reaction involves an oxidative addition/π-activation mechanism in contrast to the migratory insertion/cis-trans isomerization pathway that is predominantly observed with other transition metals yielding products with anti-selectivity. Mechanistic insights include several control experiments, NMR studies, HR-MSMS analyses, and DFT calculations that strongly support the proposed mechanism.

Electrochemical Gold-Catalyzed 1,2-Difunctionalization of C-C Multiple Bonds.

Herein, 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 31 P NMR, control experiments, mass studies, and cyclic voltammetric (CV) analysis have been performed to support the proposed reaction mechanism.

Gold-based enantioselective bimetallic catalysis.

Multimetallic catalysis is a powerful strategy to access complex molecular scaffolds efficiently from easily available starting materials. Numerous reports in the literature have demonstrated the effectiveness of this approach, particularly for capitalizing on enantioselective transformations. Interestingly, gold joined the race of transition metals very late making its use in multimetallic catalysis unthinkable. Recent literature revealed that there is an urgent need to develop gold-based multicatalytic systems based on the combination of gold with other metals for enabling enantioselective transformations that are not possible to capitalize with the use of a single catalyst alone. This review article highlights the progress made in the field of enantioselective gold-based bimetallic catalysis highlighting the power of multicatalysis for accessing new reactivities and selectivities which are beyond the reach of individual catalysts.

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 Heck Reaction.

Herein, we report a gold-catalyzed Heck reaction facilitated by the ligand-enabled Au(I)/Au(III) redox catalysis. The elementary organometallic steps such as migratory insertion and ß-hydride elimination have been realized in the catalytic fashion for the first time in gold chemistry. The present methodology not only overcomes the limitations of previously known transition metal-catalyzed Heck reactions such as the requirement of specialized substrates and formation of a mixture of regioisomeric products as a result of the undesirable chain-walking process but also offers complementary regioselectivity as compared to other transition metal catalysis.

BQ-AurIPr: a redox-active anticancer Au(i) complex that induces immunogenic cell death.

Immunogenic Cell Death (ICD) is a unique cell death mechanism that kills cancer cells while rejuvenating the anticancer immunosurveillance, thereby benefiting the clinical outcomes of various immuno-chemotherapeutic regimens. Herein, we report development of a library of benzo[a]quinolizinium-based Au(i) complexes through an intramolecular amino-auration reaction of pyridino-alkynes. We tested 40 candidates and successfully identified BQ-AurIPr as a novel redox-active Au(i) complex with potent anticancer properties. BQ-AurIPr efficiently triggered generation of DAMPs - the hallmarks of ICD - and was superior in terms of efficiency compared to FDA-approved drugs known to induce ICD. BQ-AurIPr significantly increased immunogenicity of cancer cells enhancing their phagocytosis when co-cultured with immune cells. Our investigation reveals that BQ-AurIPr induces oxidative stress inside mitochondria leading to mitophagy, as the mechanism for immunogenic cell death in A549 cells.

AIEgens Based on Anion-π+ Interactions: Design, Synthesis, Photophysical Properties, and Their Applications in Material Science and Biology.

The design of novel aggregation-induced emission luminogens (AIEgens), has generally been facilitated by disrupting the possibility of π-π stacking. The recent literature describes a novel strategy to design AIEgens by introducing anion-π+ interactions to prevent the detrimental π-π stacking. This new strategy provides access to intrinsically charged AIEgens whose photophysical properties can be tuned either by incorporating different substituents on the π-molecular scaffold to modulate the acidity for tuning the interaction energy between a π-acceptor and counter-anions. This concept article provides a brief overview of the field, focusing on the synthesis of AIEgens, their photophysical properties, crystallography studies and their applications in live cell fluorescence imaging.

Ligand-Enabled Gold-Catalyzed C(sp2)-S Cross-Coupling Reactions.

Herein we report C(sp2)-S cross-coupling reactions of aryl iodides and arylsulfonyl hydrazides under ligand-enabled, Au(I)/Au(III) redox catalysis. This strategy operates under mild reaction conditions, requires no prefunctionalized aryl coupling partner, and works across several aryl iodides. The utility of this protocol is highlighted through the synthesis of various medicinally relevant biaryl sulfones. The reaction mechanism is supported with control experiments, mass spectrometry, and NMR studies.

Enantioselective Au(I)/Au(III) Redox Catalysis Enabled by Chiral (P,N)-Ligands.

Presented herein is the first report of enantioselective Au(I)/Au(III) redox catalysis, enabled by a newly designed hemilabile chiral (P,N)-ligand (ChetPhos). The potential of this concept has been demonstrated by the development of enantioselective 1,2-oxyarylation and 1,2-aminoarylation of alkenes which provided direct access to the medicinally relevant 3-oxy- and 3-aminochromans (up to 88% yield and 99% ee). DFT studies were carried out to unravel the enantiodetermining step, which revealed that the stronger trans influence of phosphorus allows selective positioning of the substrate in the C2-symmetric chiral environment present around nitrogen, imparting a high level of enantioselectivity.

Interplay of Anion-π+ and π+ -π+ Interactions in Novel Pyrido[2,1-a]isoquinolinium-Based AIEgens - Substituent- and Counterion-Dependent Fluorescence Modulation and Applications in Live Cell Mitochondrial Imaging.

Recently, the concept of anion-π+ interactions has witnessed unique applications in the field of AIEgen development. In this contribution, we disclose a consolidated study of a library of N-doped ionic AIEgens accessed through silver-mediated cyclization of pyridino-alkynes. A thorough photophysical, computational and crystallographic study has been conducted to rationalize the observed substituent- and counterion-dependent fluorescence properties of these luminogens. We further elucidate the prominent role of anion-π+ interactions, π+ -π+ interactions and other non-covalent interactions, in inhibiting the undesired ACQ effect. Finally, we have also demonstrated the application of selected AIEgens for imaging of mitochondria in live cells.

Enantioselective C-H Functionalization Reactions under Gold Catalysis.

Transition metal-catalyzed enantioselective functionalization of ubiquitous C-H bonds has proven to be promising field as it offers the construction of chiral molecular complexity in a step- and atom-economical manner. In recent years, gold has emerged as an attractive contender for catalyzing such reactions. The unique reactivities and selectivities offered by gold catalysts have been exploited to access numerous asymmetric transformations based on gold-catalyzed C-H functionalization processes. Herein, this review critically highlights the major advances and discoveries made in the enantioselective C-H functionalization under gold catalysis which is accompanied by mechanistic insights at appropriate places.

Special Issue: Recent Advances in Transition-Metal Catalysis.

This special issue "Recent Advances in Transition-Metal Catalysis" containing forty-two personal accounts and seven record reviews, discusses the ascendancy of transition metals in modern organic synthesis. The included articles portray the manifold application of transition metals in various processes such as addition/cyclization reactions, asymmetric synthesis, olefin metathesis reactions, coupling reactions, C-H bond activation/functionalization reactions. Additionally, reports describing novel organic transformations based on the employment of transition-metal catalysis in the fields of radical chemistry and materials science are also presented in this collection.

1,2-Aminofunctionalization Reactions of Pyridino-Alkynes via Carbophilic Activation.

Transition metal-catalyzed 1,2-difunctionalization reactions of alkynes have emerged as a powerful tool to forge carbon-carbon and carbon-heteroatom bonds for the rapid synthesis of polyfunctionalized molecular scaffolds. In this regard, our group has persistently been developing transition metal-mediated 1,2-aminofunctionalization reactions of alkynes through a rationally designed pyridino-alkyne core by utilizing the carbophilic activation strategy. In this account, we present an array of such 1,2-aminofunctionalization reactions which have been successfully executed on this core to afford important polycyclic frameworks such as functionalized quinalizinones, pyridinium oxazole dyads (PODs), N-doped polycyclic aromatic hydrocarbons (PAHs), N-doped spiro-PAHs. Additionally, the synthesis of phosphine ligated gold complexes bearing pyrido-isoquinoline scaffold from the pyridino-alkynes will be discussed briefly.

The interplay of carbophilic activation and Au(I)/Au(III) catalysis: an emerging technique for 1,2-difunctionalization of C-C multiple bonds.

Gold complexes have emerged as the catalysts of choice for various functionalization reactions of C-C multiple bonds due to their inherent carbophilic nature. In a parallel space, efforts to realize less accessible cross-coupling reactivity have led to the development of various strategies that facilitate the arduous Au(I)/Au(III) redox cycle. The interplay of the two important reactivity modes encountered in gold catalysis, namely carbophilic activation and Au(I)/Au(III) catalysis, has allowed the development of a novel mechanistic paradigm that sponsors 1,2-difunctionalization reactions of various C-C multiple bonds. Interestingly, the reactivity as well as selectivity obtained through this interplay could be complementary to that obtained by the use of various other transition metals that mainly involved the classical oxidative addition/migratory insertion pathways. The present review shall comprehensively cover all the 1,2-difunctionalization reactions of C-C multiple bonds that have been realized by the interplay of the two important reactivity modes and categorized on the basis of the method that has been employed to foster the Au(I)/Au(III) redox cycle.

Divergent Gold Catalysis: Unlocking Molecular Diversity through Catalyst Control.

The catalyst-directed divergent synthesis, commonly termed as "divergent catalysis", has emerged as a promising technique as it allows chartering of structurally distinct products from common substrates simply by modulating the catalyst system. In this regard, gold complexes emerged as powerful catalysts as they offer unique reactivity profiles as compared to various other transition metal catalysts, primarily due to their salient electronic and geometrical features. Owing to the tunable soft π-acidic nature, gold catalysts not only evolved as superior contenders for catalyzing the reactions of alkynes, alkenes, and allenes but also, more intriguingly, have been found to provide divergent reaction pathways over other π-acid catalysts such as Ag, Pt, Pd, Rh, Cu, In, Sc, Hg, Zn, etc. The recent past has witnessed a renaissance in such examples wherein, by choosing gold catalysts over other transition metal catalysts or by fine-tuning the ligands, counteranions or oxidation states of the gold catalyst itself, a complete reactivity switch was observed. However, reviews documenting such examples are sporadic; as a result, most of the reports of this kind remained scattered in the literature, thereby hampering further development of this burgeoning field. By conceptualizing the idea of "Divergent Gold Catalysis (DGC)", this review aims to consolidate all such reports and provide a unified approach necessary to pave the way for further advancement of this exciting area. Based on the factors governing the divergence in product formation, an explicit classification of DGC has been provided. To gain a fundamental understanding of the divergence in observed reactivities and selectivities, the review is accompanied by mechanistic insights at appropriate places.

Ligand-enabled gold-catalyzed 1,2-heteroarylation of alkenes.

By adopting the interplay between ligand-enabled Au(i)/Au(iii) catalysis and the unique π-activation mode of gold complexes, a highly coveted 1,2-heteroarylation of alkenes has been accomplished. The present ligand-enabled approach not only circumvents the requirement for strong sacrificial oxidants or photocatalysts but also operates under mild reaction conditions by utilizing simple and non-prefunctionalized aryl coupling partners.