Reply to Correspondence on "Unlocking the Chain-Walking Process in Gold Catalysis".

We recently reported the gold-catalyzed Heck and chain-walking reactions, which utilize migratory insertion, β-hydride elimination steps in a catalytic fashion. Budzelaar et al. in their correspondence state that these reactions proceed through gold-catalyzed alkene heteroarylation followed by acid-mediated elimination and cyclization sequence.

Ligand-Enabled Gold-Catalyzed Cyanation of Organohalides.

Herein, we disclose the first report on gold-catalyzed C(sp)-CN cross-coupling reaction by employing a ligand-enabled Au(I)/Au(III) redox catalysis. This transformation utilizes acetone cyanohydrin as a nucleophilic cyanide source to convert simple aryl and alkenyl iodides into the corresponding nitriles. Combined experimental and computational studies highlighted the crucial role of cationic silver salts in activating the stable (P,N)-AuCN complex towards the oxidative addition of aryl iodides to subsequently generate key aryl-Au(III) cyanide complexes.

Gold-Catalyzed Alkoxy-Carbonylation of Aryl and Vinyl Iodides.

Herein, for the first time, we disclose the gold-catalyzed alkoxy-carbonylation of aryl and vinyl iodides utilizing ligand-enabled Au(I)/Au(III) redox catalysis. The present methodology is found to be general, efficient, employs mild reaction conditions and showcases a broad substrate scope even with structurally complex molecules. Density functional theory (DFT) calculations revealed mechanistic pathways distinct from those of conventional transition metal-catalyzed carbonylation reactions.

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.

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 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.

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 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 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.

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 β-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.

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 P NMR, deuterium labeling, and HRMS studies have been carried out to underpin mechanistic insights.

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[]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.

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.

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

Herein we report C(sp)-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.

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 influence of phosphorus allows selective positioning of the substrate in the -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.

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.

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.

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.

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.

Gold-Catalyzed Alkynylative Meyer-Schuster Rearrangement.

By applying the "interplay" mode, which consolidates two key reactivity modes of gold catalysis, namely π-activation mode and cross-coupling mode, the first alkynylative Meyer-Schuster rearrangement is designed and successfully implemented. The current protocol gives straightforward access to enynones, a highly valuable building block, from easily available propargyl alcohol feedstocks. Control experiments suggest an Au(III) catalyst triggers the Meyer-Schuster rearrangement, whereas monitoring the reaction with ESI-HRMS provided strong evidence in favor of a key alkynylgold(III) intermediate which supports the proposed "interplay" scenario.

Gold-Catalyzed 1,2-Diarylation of Alkenes.

Herein, we disclose the gold-catalyzed 1,2-diarylation of alkenes through the interplay of ligand-enabled Au /Au catalysis with the idiosyncratic π-activation mode of gold complexes. Unlike the classical migratory-insertion-based approach to 1,2-diarylation, the present approach not only circumvents the formation of direct Ar-Ar' coupling and Heck-type side products but more intriguingly demonstrates reactivity and selectivity complementary to those of previously known metal catalysis (Pd, Ni, or Cu). Detailed investigations to underpin the mechanistic scenario revealed oxidative addition of aryl iodides to an Au complex to be the rate-limiting step owing to the non-innocent nature of the aryl alkene.