Copper‐Catalyzed Intermolecular Asymmetric Propargylic Dearomatization of Indoles

The first copper‐catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.     

Gold‐Catalyzed Cyclization Leads to a Bridged Tetracyclic Indolenine that Represses β‐Lactam Resistance

A gold‐catalyzed desilylative cyclization was developed for facile synthesis of bridged tetracyclic indolenines, a common motif in many natural indole alkaloids. An antimicrobial screen of the cyclization products identified one compound which selectively potentiates β‐lactam antibiotics in methicillin‐resistant S. aureus (MRSA), and re‐sensitizes a variety of MRSA strains to β‐lactams.     

Bifunctional Ligand Enables Efficient Gold‐Catalyzed Hydroalkenylation of Propargylic Alcohol

Using the previously designed biphenyl‐2‐ylphosphine ligand, featuring a remote tertiary amino group, the first gold‐catalyzed intermolecular hydroalkenylation of alkynes has been developed. Synthetically valuable conjugated dienyl alcohols are formed in moderate to good yields. A range of alkenyltrifluoroborates are allowed as the alkenyl donor, and no erosion of alkene geometry and/or the propargylic configuration are detected. DFT calculations confirm the critical role of the remote basic group in the ligand as a general‐base catalyst for promoting this novel gold catalysis with good efficiency.     

Copper‐Catalyzed Skeletal Rearrangements of O‐Propargylic Oximes via Cleavage of a Carbon–Oxygen Bond

In this account, we describe recent developments in copper‐catalyzed skeletal 2,3‐rearrangement reactions of O‐propargylic oximes to form four‐membered cyclic nitrones, pyridine N‐oxides, and amidodienes via N‐allenylnitrone intermediates. The sequence of events leading up to our encounter with O‐propargylic oximes is also presented.     

Gold‐Catalyzed 1,2‐Oxoarylations of Nitriles with Pyridine‐Derived Oxides

We report the first success in the gold‐catalyzed oxoarylations of nitriles with pyridine‐derived N‐oxides using gold carbenes as initiators. These oxoarylations were also achieved satisfactorily in intermolecular three‐component oxidations, including diverse alkenyldiazo esters, nitriles, and pyridine‐based oxides.     

Copper‐Catalyzed Cyclization/aza‐Claisen Rearrangement Cascade Initiated by Ketenimine Formation: An Efficient Stereocontrolled Synthesis of α‐Allyl Cyclic Amidines

An efficient and convenient synthesis of α‐allyl cyclic amidines has been achieved by applying a novel cascade reaction. Copper(I)‐mediated in situ N‐sulfonyl ketenimine formation from the reaction of a terminal alkyne with sulfonyl azide is followed by an intramolecular nucleophilic attack on the central carbon atom by an allylic tertiary amine, and then an aza‐Claisen rearrangement takes place through a chair transition state to furnish the titled amidines with complete stereocontrol.     

Copper‐Catalyzed Trifluoromethylazidation of Alkynes: Efficient Access to CF3‐Substituted Azirines and Aziridines

A novel method for convenient access to CF₃‐containing azirines has been developed, and involves a copper‐catalyzed trifluoromethylazidation of alkynes and a photocatalyzed rearrangement. Both terminal and internal alkynes are compatible with the mild reaction conditions, thus delivering the CF₃‐containing azirines in moderate to good yields. The azirines can be converted into various CF₃‐substituted aziridines.     

Gold‐Catalyzed C(sp3)H/C(sp)H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans

In sharp contrast to the gold‐catalyzed reactions of alkynes/allenes with nucleophiles, gold‐catalyzed oxidative cross‐couplings and especially C? H/C? H cross‐coupling have been under represented. By taking advantage of the unique redox property and carbophilic π acidity of gold, this work realizes the first gold‐catalyzed direct C(sp³)? H alkynylation of 1,3‐dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region‐defined approach to 3‐alkynyl polysubstituted furans.     

Application of Fundamental Organometallic Chemistry to the Development of a Gold‐Catalyzed Synthesis of Sulfinate Derivatives

The development of a gold(I)‐catalyzed sulfination of aryl boronic acids is described. This transformation proceeds through an unprecedented mechanism which exploits the reactivity of gold(I)–heteroatom bonds to form sulfinate anions. Further in situ elaboration of the sulfinate intermediates leads to the corresponding sulfones and sulfonamides, two pharmacophores routinely encountered in drug discovery.     

Gold‐Catalyzed Cyclization Processes: Pivotal Avenues for Organic Synthesis

Over the years, gold catalysis has materialized as an incredible synthetic approach among the scientific community. Due to the trivial reaction conditions and great functional compatibility, these progressions are synthetically expedient, because practitioners can implement them to build intricate architectures from readily amassed building blocks with high bond forming indices. The incendiary growth of gold catalysts in organic synthesis has been demonstrated as one of the most prevailing soft Lewis acids for electrophilic activation of carbon‐carbon multiple bonds towards a great assortment of nucleophiles. Nowadays, organic chemists consistently employ gold catalysts to carry out a diverse array of organic transformations to build unprecedented molecular architectures. Despite all these achievements and a plethora of reports, many vital challenges remain. In this account, we describe the reactivity of various gold catalysts towards cyclization processes developed over the years. These protocols give access to a wide scope of polyheterocyclic structures, containing different medium‐sized ring skeletons. This is interesting, as the quest for highly selective reactions to assemble diversely functionalized products has attracted much attention. We envisage that these newly developed chemo‐, regio‐, and diastereoselective protocols could provide an expedient route to architecturally cumbersome heterocycles of importance for the pharmaceutical industry.     

Gold‐Catalyzed Oxa‐Povarov Reactions for the Synthesis of Highly Substituted Dihydrobenzopyrans from Diaryloxymethylarenes and Olefins

Oxa‐Povarov reactions involving readily available diaryloxymethylarenes and aryl‐substituted alkenes are reported. Their [4+2] cycloadditions were efficiently catalyzed by IPrAuSbF₆ (IPr=1,3‐bis(diisopropylphenyl)imidazol‐2‐ylidene) with high diastereoselectivity. Product analysis revealed that the reactions likely proceed by a stepwise ionic mechanism, because both E‐ and Z‐configured β‐methylstyrene gave the same cycloadducts in the same proportions.     

Gold(I)‐Catalyzed Tandem Cycloisomerization of 1,5‐Enyne Ethers by Hydride Transfer

A novel gold‐catalyzed tandem protocol, initiated by hydride transfer in the presence of catalytic (C₆F₅)₃PAuCl/AgSbF₆, for the formation of fused polycyclic ring systems has been achieved. This tandem reaction provides rapid access to various fused polycyclic species in a single chemical operation, leading to stereospecific formation of two carbon–carbon bonds and three rings.     

A Gold‐Catalyzed Domino Cyclization Enabling Rapid Construction of Diverse Polyheterocyclic Frameworks

We report herein an efficient gold(I)‐catalyzed post‐Ugi domino dearomatization/ipso‐cyclization/Michael sequence that enables access to libraries of diverse (hetero)arene‐annulated tricyclic heterocycles. This process affords novel complex polycyclic scaffolds in moderate to good yields from readily available acyclic precursors with excellent chemo‐, regio‐, and diastereoselectivity. The power of this strategy has been demonstrated by the rapid synthesis of 40 highly functionalized polyheterocycles bearing indole, pyrrole, (benzo)furan, (benzo)thiophene, pyrazole, and electron‐rich arene groups in two operational steps.