Gold-catalyzed Reactions Research Articles

Synthesis of 1,3,5-trisubstituted 1,2,4-triazoles enabled by a gold-catalyzed three-component reaction

Valuable fully substituted 1,2,4-triazoles are obtained via a gold-catalyzed three-component reaction involving ethyl diazoacetate, aryldiazonium salts, and nitriles. The reaction proceeds under mild conditions, is regioselective, and allows the introduction of mono- and di-substituted aryl rings at the ortho, meta, and para positions. Mechanistic evidence suggests the participation of Au(III) species as the active catalysts.

Au(I)/Au(III)-Catalyzed Sulfonylation of Aryl Iodides for the Synthesis of Various Functionalized Aryl Sulfones.

A gold-catalyzed sulfonylation reaction of aryl iodides with different sodium sulfinates facilitated by the ligand-enabled Au(I)/Au(III) redox catalysis was developed. In the reaction of gold-catalyzed C-S coupling, a variety of functionalized sodium sulfinates, such as CF3, CHF2, CH3, and alkyl groups, can react smoothly with aryl iodides to directly construct diversely functionalized aryl sulfones. This gold-catalyzed sulfonylation offers a complementary method for synthesizing functionalized aryl sulfones with electron-donating groups.

Gold-Catalyzed Synthesis of 5H-Benzo[b]indeno[2,1-d]silines by Insertion of Vinyl Carbocations into the Si-H Bond.

We have developed a gold-catalyzed cascade reaction of aryldiynes bearing a hydrosilyl group to afford a variety of unexplored 5H-benzo[b]indeno[2,1-d]silines. The reaction system is applicable to the synthesis of bidirectionally π-extended silacycles from tetra(alkynyl)aryl compounds. Computational studies suggest that 5H-benzo[b]indeno[2,1-d]silines are formed via the insertion of a vinyl carbocation intermediate into the Si-H bond.

Regiodivergent Gold-Catalyzed Rearrangement-Addition Reactions of Sulfenylated Propargylic Carboxylates with Indoles.

Sulfenylated propargylic carboxylates were introduced to investigate the influence of sulfur substitution in gold-catalyzed alkyne activation pathways. Regiodivergent gold-catalyzed rearrangement and indole capture reactions proceed under mild conditions to give functionalized indole products bearing sulfenylated (Z)-enol carboxylate motifs. Pathways involving both 1,2- and 1,3-carboxylate migrations are achieved selectively, with indole being added in a 1,4 relationship to the sulfenyl group in each case. High levels of selectivity are influenced by the catalyst system, counterion, and carboxylate group.

Gold(III) Auracycles Featuring C(sp3)-Au-C(sp2) Bonds: Synthesis and Mechanistic Insights into the Cycloauration Step.

The direct auration of arenes is a key step in numerous gold-catalyzed reactions. Although reported more than 100 years ago, understanding of its underlying mechanism has been hampered by the difficulties in the isolation of relevant intermediates given the propensity of gold(III) species to undergo reductive elimination. Here, we report the synthesis and isolation of a new family of intriguing zwitterionic [C(sp3)^C(sp2)]-auracyclopentanes, as well as of their alkyl-gold(III) precursors and demonstrate their value as mechanistic probes to study the C(sp2)-Au bond-forming event. Experimental investigations employing Kinetic Isotope Effects (KIE), Hammett plot, and Eyring analysis provided important insights into the formation of the auracycle. The data suggest a SEAr mechanism wherein the slowest step might be the π-coordination between the arene and the gold(III) center, en route to the Wheland intermediate. We also show that these auracyclopentanes can work as catalysts in several gold-promoted transformations.

Some New Aspects of Gold-Catalyzed Benzannulation Reaction

Introduction: The gold-catalyzed benzannulation reaction of oxo-alkynes with al-kenes or alkynes is one of the important and unique reactions in gold-catalyzed organic trans-formations. Methods: In this manuscript, many facets of this reaction have been discussed concerning reac-tivity and selectivity, along with a new self-benzannulation process. The scope of this chemistry was extended to construct a phenanthrene moiety. Results: In addition, a palladium-gold dual catalytic arylation of isobenzopyrylium salts using arene-diazonium salts as an aryl group source and a one-pot isoquinoline synthesis is reported for the first time. Conclusion: Moreover, a conductance measurement experiment was performed, which supports the formation of ionic species, most likely the isobenzopyrylium auric ate complex as an inter-mediate formed during the reaction process.

Stereoselective Double Spirocyclization of 2-Benzyl-3-alkynyl Chromone with Nitrone via Gold-Catalyzed Cascade Reactions.

A novel, highly stereoselective gold-catalyzed spirocyclization of 2-benzyl-3-alkynyl chromone with nitrone is described. This cascade reaction involves gold-catalyzed cycloisomerization, nitrone-olefin [3 + 2]-annulation, alkene oxidation, and rearrangement for the formation of spirocyclic products. Interestingly, the isoxazolidine ring generated from [3 + 2]-annulation donates oxygen to alkene to generate a new pyran-3(4H)-one and azetidine ring for dispiro-benzofuran formation upon heating. This work demonstrates the one-pot, gold-catalyzed, multiple-step reaction, and the reaction temperature directly affects the formation of spirocyclic products.

Straightforward Access to Isoindoles and 1,2-Dihydrophthalazines Enabled by a Gold-Catalyzed Three-Component Reaction.

We describe herein a gold-catalyzed three-component reaction of o-alkynylbenzaldehydes, aryldiazonium salts, and trimethoxybenzene. This process enables the one-pot formation of valuable isoindoles and 1,2-dihydrophathalazines. The regioselectivity of the reaction is dictated by the nature of the aryldiazonium salt. Noticeably, the reaction is performed at room temperature under mild conditions and tolerates a variety of functional groups on both the o-alkynylbenzaldehyde and the aryldiazonium salt. Experimental mechanistic studies suggest that it is catalyzed by arylAu(III) species.

The Potential of Self-Activating Au(I) Complexes in Gold Catalysis.

Gold catalysis has emerged as a groundbreaking field in synthetic chemistry, revolutionizing numerous organic transformations. Despite the significant achieved advancements, the mechanistic understanding behind many gold-catalyzed reactions remains elusive. This Concept article covers the so-called "self-activating" Au(I) complexes, sorting out their pivotal role in gold catalysis. We comment on how Au(I) complexes can undergo self-activation, triggering diverse catalytic transformations without the need for external additives. The most important examples reported so far that underlie the catalytic activity of these species are discussed. This intrinsic reactivity represents a paradigm shift in gold catalysis, offering new avenues for the design of efficient and sustainable catalytic systems. Furthermore, we explore the factors influencing the stability, reactivity, and selectivity of these Au(I) complexes, providing insights into their synthetic utility and potential applications. This area of research not only advances our fundamental understanding of gold catalysis but also paves the way for the development of novel catalytic strategies with broad implications in organic synthesis and the chemical industry.

Gold catalysis in quinoline synthesis.

Quinolines are biologically and pharmaceutically important N-heterocyclic aromatic compounds, which have broad applications in medicinal chemistry. Thus, their efficient synthesis has attracted extensive attention, and a broad range of synthetic strategies have been established. Of note, gold-catalyzed methodologies for the synthesis of quinolines have greatly advanced this field. Various gold-catalyzed intermolecular annulation reactions, such as annulations of aniline derivatives with carbonyl compounds or alkynes, annulations of anthranils with alkynes, and annulations based on A3-coupling reactions, as well as intramolecular cyclization reactions of azide-tethered alkynes, 1,2-diphenylethynes, and 2-ethynyl N-aryl indoles, have been developed. This review provides an overview of this exciting research area. Typical achievements in reaction methodologies and plausible reaction mechanisms are summarized.

An Efficient and Scalable "Second Generation" Total Synthesis of the Marine Polyketide Limaol Endowed with Antiparasitic Activity.

The cluster of four skipped exo-methylene substituents on the "northern" wing of limaol renders this dinoflagellate-derived marine natural product unique in structural terms. This arguably non-thermodynamic array gains kinetic stability by virtue of populating local conformations which impede isomerization to a partly or fully conjugated polyene. This analysis suggested that the difficulties encountered during the late stages of our first total synthesis of this polyketide had not been caused by an overly fragile character of this unusual substructure; rather, an unfavorable steric microenvironment about the spirotricyclic core was identified as the likely cause. To remedy the issue, the protecting groups on this central fragment were changed; in effect, this amendment allowed all strategic and practical problems to be addressed. As a result, the overall yield over the longest linear sequence was multiplied by a factor of almost five and the material throughput increased more than eighty-fold per run. Key-to-success was a gold-catalyzed spirocyclization reaction; the reasons why a Brønsted acid cocatalyst is needed and the origin of the excellent levels of selectivity were delineated. The change of the protecting groups also allowed for much improved fragment coupling processes; most notably, the sequence of a substrate-controlled carbonyl addition reaction followed by Mitsunobu inversion that had originally been necessary to affix the southern tail to the core could be replaced by a reagent controlled asymmetric allylation. Finally, a much-improved route to the "northern" sector was established by leveraging the power of asymmetric hydrogenation of a 2-pyrone derivative. Limaol was found to combine appreciable antiparasitic activity with very modest cytotoxicity.

Gold-catalyzed Reactions of Substituted 1,5-diynes: Recent Advances and their Chemistry

Abstract: Diynes are identified as exceptionally potent and superior substrates in gold-catalyzed organic transformations. Gold (I) and gold (III) complexes exhibit unique activity towards diynes, encouraging the nucleophilic addition of different functional groups both inter and intra- molecularly. In this review, particularly, we focused on recent advances in gold-catalyzed reactions of 1,5-diynes along with their mechanistic aspects. These reactions are interesting for constructing molecular complexity, medicinal chemistry, and material science.

1,2-Silyl Rearrangement in Gold Carbene Chemistry: Synthesis of Furyl-Decorated Tetrasubstituted Silylallene Derivatives.

The gold-catalyzed reaction of 2-en-4-ynones with alkynylsilanes provides fully substituted allene derivatives bearing furyl and silyl groups. This transformation would involve generation of a gold furyl carbene intermediate, which regioselectively undergoes a nucleophilic attack by the alkynylsilane at the electrophilic carbene carbon atom with the formation of a β-gold vinyl cation species. The subsequent release of the gold catalyst, accompanied by a 1,2-silyl shift, leads to the formation of tetrasubstituted allene products.

Gold-Catalyzed Cascade Reaction of Yne-Enones with Iminooxindoles, Access to 3,2'-Pyrrolidinyl-Spirooxindole Derivatives.

Herein, a gold-catalyzed cascade reaction of yne-enones with iminooxindoles has been developed through a cascade cycloisomerization/(3 + 2) annulation process. This approach provides a straightforward and efficient route for the synthesis of functionalized 3,2'-pyrrolidinyl-spirooxindoles in high reactivity and broad substrate scope with excellent cis-selectivity. Moreover, the subsequent functionalization of furan units allows for the diverse synthesis of spirooxindole derivatives, which have demonstrated good antitumoral activity.

Gold(I)-Catalyzed Intramolecular 7-endo-dig Cyclization of Triene-Yne Systems: New Access towards Azulenothiophenes.

We report the direct synthesis of new azulene derivatives through gold-catalyzed cyclization reactions. A five-membered ring as backbone in the applied triene-yne substrates turned out to be crucial to induce the 7-endo-dig cyclization mode necessary to trigger azulene formation. The obtained targets are of high interest due to their potential applications in different fields, like organic materials, medicine or cosmetics. UV/Vis spectra and cyclic voltammetry were measured, based on these the electronic properties were determined. Short two or three step sequences towards the applied starting materials make this approach synthetically highly attractive.

Gold-Catalyzed Reactions of Enynals with Alkenes for Synthesis Binaphthyl Derivatives.

A PPh3Au[B(C6F5)4]-catalyzed reaction of enynals and alkenes for the construction of binaphthyl derivatives was described. This transformation was achieved through o-Quinodimethane (o-QDM) intermediate's extended conjugated addition process. The reaction has the advantages of wide substrate scopes, mild reaction conditions, high efficiency, and good scalability.

Gold-Catalyzed Oxidation Reactions of Thioalkynes with Quinoline N-Oxides: A DFT Study.

Mechanistic investigation of the gold-catalyzed oxidative reactions of thioalkynes with quinoline N-oxides was performed using density functional theory (DFT) calculations. For the oxidative rearrangement of thioalkynes with quinoline N-oxide to yield the same products, the Cβ-oxidation of thioalkynes was predicted to be competitive with Cα-oxidation, with the Cβ-oxidative process slightly more favorable. However, for the oxidative alkenylation of propargyl aryl thioethers with quinoline N-oxides, the Cβ-oxidation of thioether by quinoline N-oxide generated the product 3-hydroxy-1-alkylidene phenylthiopropan-2-one. Moreover, the ring opening of the four-membered sulfonium intermediate was achieved by the nucleophilic attack of quinoline N-oxide rather than a water molecule.

Gold-catalyzed intermolecular amination of allyl azides with ynamides: efficient construction of 3-azabicyclo[3.1.0] scaffold

Gold-catalyzed amination reactions based on azides via α-imino gold carbene intermediates have attracted extensive attention in the past decades because this methodology leads to the facile and efficient construction of synthetically useful N-containing molecules, especially valuable N-heterocycles. However, successful examples of intermolecular generation of α-imino gold carbenes by using azides as amination reagents are rarely explored probably due to the weak nucleophilicity of azides. Herein, we disclose an efficient gold-catalyzed intermolecular aminative cyclopropanation of ynamides with the allyl azides, enabling flexible synthesis of a wide range of valuable 3-azabicyclo[3.1.0]hex-2-ene derivatives in good to excellent yields with excellent diastereoselectivities. Importantly, this protocol represents the first use of allyl azide as an efficient amination reagent in gold-catalyzed alkyne amination reactions.

Syn-Aminoauration versus Anti-Aminoauration of Alkynes in Au(I)/Au(III) Catalysis: Understanding the Origin of Selectivity.

There is no experimental evidence of whether such gold-catalyzed aminoauration reactions follow the anti- and/or syn-pathway, and hence, to understand the origin of the selectivity in Au(I)- and Au(III)-catalyzed reactions of alkynes, a thorough mechanistic study was performed using DFT methods. The NBO and ASM analyses provided significant information about the structure-stability-reactivity of the pathway-determining states (PDS). This study further reveals that the oxidation states and geometries of gold, the steric bulk, and the dihedral angles of the PDS direct the mechanistic pathways and control the turnover frequency.

Synthesis of the I-K Fused Polyether Array of CTX3C and Related Ciguatoxins by Use of a Gold-Catalyzed Cyclization Reaction.

The I-K fragment (C31-C49) of the ciguatoxin CTX3C has been synthesized from a simple chiral pool derived tetrahydropyranyl alcohol. An efficient gold-catalyzed cyclization reaction of a γ'-hydroxy ynone has been used to accomplish efficient closure of ring K under mild conditions. The resulting vinylogous ester has been elaborated to give a complete tricyclic fragment bearing the dimethyl-substituted side chain required for assembly of the LM spirocyclic acetal portion of the target.