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.     

Formal [4+2] Reaction between 1,3‐Diynes and Pyrroles: Gold(I)‐Catalyzed Indole Synthesis by Double Hydroarylation

Indole synthesis by a gold(I)‐catalyzed intermolecular formal [4+2] reaction between 1,3‐diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3‐diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7‐disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles.     

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.     

Metal‐Catalyzed Cyclization Reactions of 2,3,4‐Trien‐1‐ols: A Joint Experimental–Computational Study

Controlled preparation of tri‐ and tetrasubstituted furans, as well as carbazoles has been achieved through chemo‐ and regioselective metal‐catalyzed cyclization reactions of cumulenic alcohols. The gold‐ and palladium‐catalyzed cycloisomerization reactions of cumulenols, including indole‐tethered 2,3,4‐trien‐1‐ols, to trisubstituted furans was effective, due to a 5‐endo‐dig oxycyclization by attack of the hydroxy group onto the central cumulene double bond. In contrast, palladium‐catalyzed heterocyclization/coupling reactions with 3‐bromoprop‐1‐enes furnished tetrasubstituted furans. Also studied was the palladium‐catalyzed cyclization/coupling sequence involving protected indole‐tethered 2,3,4‐trien‐1‐ols and 3‐bromoprop‐1‐enes that exclusively generated trisubstituted carbazole derivatives. These results could be explained through a selective 6‐endo‐dig cumulenic hydroarylation, followed by aromatization. DFT calculations were carried out to understand this difference in reactivity.     

Carbazoles from the [4C+2C] Reaction of 2,3‐Allenols with Indoles

A mild and efficient method using readily available 1‐aryl‐2,3‐allenols and unprotected‐N indoles, Au⁺‐catalyzed cyclization, and aromatization to afford the final [4C+2C] products, carbazoles 4, with an excellent selectivity, is reported. The reaction demonstrates excellent regioselectivity and allows the N?H unit to undergo reactivity unprotected. A mechanism involving a spiropolycyclic intermediate has been proposed and synthetic application is also demonstrated.     

Gold‐Catalyzed CH Annulation of Anthranils with Alkynes: A Facile,Flexible, and Atom‐Economical Synthesis of Unprotected 7‐Acylindoles

The gold‐catalyzed C? H annulation of anthranil derivatives with alkynes offers a facile, flexible, and atom‐economical one‐step route to unprotected 7‐acylindoles. An intermediate α‐imino gold carbene, generated by an intermolecular reaction, promotes ortho‐aryl C? H functionalization to afford the target products. The transformation proceeds with a broad range of substrates under mild conditions. Moreover, the obtained functionalized indole products represent a versatile platform for the construction of diverse indolyl frameworks.     

Gold‐Catalyzed Cascade Reactions for Synthesis of Carbo‐ and Heterocycles: Selectivity and Diversity

This account describes our recent efforts devoted to gold chemistry since 2009. Based on furyl–Au 1,3‐dipole analogues and related gold carbene intermediates, a rich variety of gold‐catalyzed cascade reactions have been developed, which provide facile access to a diverse range of novel carbo‐ and heterocycles. In these reactions, the selectivity can be well controlled by the catalyst (ligand and metal), substrate or reagent. In addition, we have also developed the corresponding enantioselective variants, which are guided by bis(phosphinegold) complexes derived from axially chiral scaffolds and asymmetric gold/chiral Brønsted acid relay catalysis.     

Iron‐Catalyzed Intramolecular C(sp2)−H Amination

The nucleophilic iron complex Bu₄N[Fe(CO)₃(NO)] (TBA[Fe]) catalyzes the direct intramolecular C?H amination of α‐azidobiaryls and (azidoaryl)alkenes into the corresponding carbazoles and indoles, respectively, under mild conditions and with low catalyst loadings. These features and the broad functional‐group tolerance render this method a particularly attractive alternative to established noble‐metal‐based procedures.