Zhonghua Xia

Gold(I) catalysis sous lumière visible: Cette thèse s'intéresse à l'étude d'un double processus catalytique, la catalyse à l'or et la photocatalyse. Nous avons cherché à synthétiser des dérivés enzofuranique à partir d'o-alkynylphénols et de sels d'aryle diazonium ou d'iodoalcynes en présence d'un mélange catalytique d'un complexe d'or (I) et d'un photocatalyseur sous irradiation à la lumière visible. Dans un premier temps, nous présentons un nouveau procédé de catalyse duale photoredox/or par cyclisation arylative d'o-alkynylphénols avec des sels d'aryle diazonium. Cette réaction s'effectue dans des conditions douces à température ambiante en l'absence de base et/ou d'additifs et offre une approche efficace pour la formation de squelettes hétérocycliques. La réaction proposée fait intervenir un intermédiaire vinyl or(III) formé par addition du radical aryle sur le catalyseur d'or et par modulation de l'état d‟oxydation du complexe par le photocatalyseur. Après élimination réductrice le produit de couplage hétérocyclique est obtenu. Dans un deuxième temps, nous avons mis au point une nouvelle méthode pour la synthèse de dérivés alcynylbenzofuraniques élaborés à partir d'o-alkynylphénols et d'iodoalkynes en présence d'un mélange catalytique d'Au (I) et d'Ir (III) sous irradiation de LEDs bleues. Sous irradiation à la lumière visible, le triplet excité de l'intermédiaire vinyl-or(I) et de l'iodure d‟alcyne partenaire s'engage facilement dans une séquence d'isomérisation par addition trans-cis-oxydante, enfin l'élimination réductrice permets la formation des produits de couplage croisé Csp2-Csp. Les études mécanistiques et de modélisation ont mis en évidence un phénomène de transfert d'énergie plutôt qu'un processus redox. Ce double procédé catalytique or/photoredox fournit un nouveau mode d'activation dans la catalyse homogène à l'or.

We have developed a ligand-enabled Au(I)/Au(III) catalyzed N-1 arylation of indazoles using aryl iodides as electrophile reagents. This transformation proceeds with excellent regioselectivity and a broad substrate scope, tolerating both aryl iodides with diverse electronic properties (e.g., -Br, Cl, -CO₂Me, -CHO) and a wide range of indazole derivatives.

Enones serve as versatile scaffolds in synthetic chemistry, enabling diverse transformations while exhibiting biologically relevant properties crucial for drug development. Herein, we report a ligand-enabled gold-catalyzed arylative Meyer-Schuster rearrangement employing readily available and stable propargylic acetates and aryl iodides under mild conditions. This method efficiently delivers α-arylated enones with a broad substrate scope and air-tolerant conditions, while avoiding the need for strong external oxidants or photocatalytic activation of aryl diazonium salts.

A gold-catalyzed C–N ₃ cross-coupling of aryl iodides with trimethylsilyl azide (TMSN ₃ ) was achieved via ligand-enabled Au( i )/Au( iii ) redox catalysis.

Alkynyl-containing molecules hold significant importance in organic synthesis, drug discovery, and materials science. Herein, we report an efficient protocol for the C(sp)-C(sp³) cross-coupling of bromoalkynes with primary, secondary, and tertiary alkylboronic acids. Mechanistic experiments suggest that silver and base enable the generation of an alkyl radical intermediate from the alkylboronic acid and then undergo a cascade of α-addition and β-elimination with alkynyl bromides, leading to the construction of C(sp)-C(sp³) bonds. This strategy features readily available starting materials, diverse substrates, and mild and easily handled reaction conditions.

Thioethers and their derivatives play important roles in synthetic chemistry, medicinal chemistry, and materials science. Herein, we report a hemilabile P,N-ligand-assisted gold-catalyzed C-S cross-coupling reaction of organoiodides with disulfides. In this reaction, alkyl or aryl disulfides react smoothly with aryl or vinyl iodides to afford a series of aryl sulfide and vinyl sulfide derivatives in good to excellent yields. The robust synthetic capabilities of thioether synthesis are exemplified by the readily available and easily handled reagents as well as the excellent compatibility with a wide range of functional groups.

Recently, ligand-promoted Au(I)/Au(III)-catalyzed cross-coupling reactions with aryl iodides have garnered considerable attention. Here, we report the first visible-light-driven gold-catalyzed cross-couplings of challenging aryl bromides. In the presence of a (P, N)-gold(I) catalyst and an acridinium photocatalyst under blue LED irradiation, C-O coupling of aryl bromides with carboxylic acids was achieved, and soon it was found that this photoinduced gold-catalyzed cross-coupling of aryl bromides was appliable for other C-C, C-N, and C-S bond formation. Experimental and computational studies suggest that this visible-light-driven gold-catalyzed cross-couplings of aryl bromides involves two discrete photoinduced energy transfer (EnT) events: first, energy transfer (EnT) from a photosensitizer produces an excited-state gold(I) complex that allows the bottleneck oxidative addition of aryl bromides to form an aryl Au(III) complex and second, the reductive elimination of aryl-Au(III) complex to regenerate Au(I). Collectively, the new synergistic catalytic method developed here highlights the tremendous potential of photochemical gold catalysis via excited-state organogold complexes, as well as its potential to facilitate drug discovery due to the biocompatibility and mildness of the reaction conditions.

A gold-catalyzed sulfonylation of aryl/vinyl iodides to synthesize aryl sulfones facilitated by the ligand-enabled Au(I)/Au(III) redox catalysis was developed. In the reaction, aryl sodium sulfinates or sulphinic acids can react smoothly with aryl/vinyl iodides to directly construct various aryl sulfones. The strong synthetic capabilities of sulfone synthesis are demonstrated by its easily available and handled reagents, good functional group compatibility, and late-stage application of complicated biomolecules. Mechanistic studies suggest that the silver salt plays a crucial role in the transmetalation with the Au(I)/Au(III) intermediate, and the gold complex favors Au-S bond formation over Au-O bond formation.

An efficient silver‐mediated allylation of aryl alkenes is described, which provides a variety of skipped 1,4‐dienes. Without the need for other traditional transition metals or gold, this AgOTf‐mediated allylation proceeds smoothly with high regio‐ and stereoselectivity. Mechanistic and computational studies suggest that this silver‐mediated allylation takes place via a Friedel−Crafts‐type pathway of aryl alkenes to the silver‐activated allyl acetates.