Acidic Co‐Catalysts in Cationic Gold Catalysis

A systematic study on the effects of Lewis or Brønsted acid co‐catalysts in gold‐catalyzed reactions was undertaken using representative reactions (O‐, N‐, and C‐nucleophilic additions to alkynes). Through these reactions, it was demonstrated that an acidic co‐catalyst can increase the catalyst turnover significantly, enabling practical reaction rates at competitive catalyst loadings (<1 mol %). Further investigation is currently underway to improve the understanding of the subtle principles underlying these experimental observations.     

Observing Initial Steps in Gold‐Catalyzed Alkyne Transformations by Utilizing Bodipy‐Tagged Phosphine–Gold Complexes

The Pd‐catalyzed reactions of 3‐chloro‐bodipy with R₂PH (R=Ph, Cy) provide nonfluorescent bodipy–phosphines 3‐PR₂–bodipy 3 a (R=Ph) and 3 b (R=Cy; quantum yield Φ<0.001). Metal complexes such as [AgCl( 3 b )] and [AuCl( 3 b )] were prepared and shown to display much higher fluorescence (Φ=0.073 and 0.096). In the gold complexes, the level of fluorescence was found to be qualitatively correlated with the electron density at gold. Consequently, the fluorescence brightness of [AuCl( 3 b )] increases when the chloro ligand is replaced by a weakly coordinating anion, whereas upon formation of the electron‐rich complex [Au(SR)( 3 b )] the fluorescence is almost quenched. Related reactions of [AuCl( 3 b )] with [Ag]ONf)] (Nf= nonaflate) and phenyl acetylenes enable the tracking of initial steps in gold‐catalyzed reactions by using fluorescence spectroscopy. Treatment of [AuCl( 3 b )] with [Ag(ONf)] gave the respective [Au(ONf)( 3 b )] only when employing more than 2.5 equivalents of silver salt. The reaction of the “cationic” gold complex with phenyl acetylenes leads to the formation of the respective dinuclear cationic [{( 3 b )Au}₂(CCPh)]⁺ and an increase in the level of fluorescence. The rate of the reaction of [Au(ONf)( 3 b )] with PhCCH depends on the amount of silver salt in the reaction mixture; a large excess of silver salt accelerates this transformation. In situ fluorescence spectroscopy thus provides valuable information on the association of gold complexes with acetylenes.     

Gold(I)‐Catalyzed Addition of Silylacetylenes to Acylsilanes: Synthesis of Indanones by CH Functionalization through a Gold(I) Carbenoid

A gold(I)‐catalyzed synthesis of indanones from trimethylsilylacetylenes and acylsilanes is presented. The reaction is initiated through a synergistic acylsilane activation–gold acetylide formation and involves consecutive alkyne σ‐gold(I) addition, π‐activation, and 1,2‐migration of a silyl group. Studies performed on the reaction mechanism allowed to establish the nature of the silyl migrating group and invoke the participation of a gold(I) carbenoid intermediate. The reaction is completed by a gold(I) C? H functionalization step.     

Gold(I)‐Catalyzed Diazo Cross‐Coupling: A Selective and Ligand‐Controlled Denitrogenation/Cyclization Cascade

An unprecedented gold‐catalyzed ligand‐controlled cross‐coupling of diazo compounds by sequential selective denitrogenation and cyclization affords N‐substituted pyrazoles in a position‐switchable mode. This novel transformation features selective decomposition of one diazo moiety and simultaneous preservation of the other one from two substrates. Notably, the choice of the ancillary ligand to the gold complex plays a pivotal role on the chemo‐ and regioselectivity of the reactions.     

Dual Hard/Soft Gold Catalysis: Intermolecular Friedel–Crafts‐Type α‐Amidoalkylation/Alkyne Hydroarylation Sequences by N‐Acyliminium Ion Chemistry

Gold catalysts have been applied in cascade‐type reactions for the synthesis of different nitrogen‐based compounds. The reactions likely proceed by a new gold‐catalyzed cascade intermolecular α‐amidoalkylation/intramolecular carbocyclization cascade process by unifying both the σ‐ and π‐Lewis acid properties of the gold salts. In the first part of this report we show that the σ‐Lewis acidity of gold(I) and gold(III) could be exploited to efficiently catalyze the nucleophilic substitution of various alkoxy‐ and acetoxylactams. The reaction was found to be applicable to a wide range of cyclic N‐acyliminium ion precursors and various nucleophiles, including allyltrimethylsilane, silyl enol ethers, arenes, and active methylene derivatives. As a logical progression of this study, a combined hard/soft binary catalytic gold system was then used to implement an unprecedented tandem intermolecular Friedel–Crafts amidoalkylation/intramolecular hydroarylation sequence allowing an expedient access to new, complex, fused polyheterocyclic structures from trivial materials.     

Gold(I)‐Catalyzed Selective Heterocyclization of Propargylic Thioureas: Mechanistic Study of Competitive Gold‐Activation Mode

A new selective gold(I)‐catalyzed intramolecular heterocyclization of propargylic thioureas has been developed, efficiently affording two kinds of cycloadducts in moderate to excellent yields with a broad substrate scope. Further mechanistic investigations indicate that competitive different gold activation modes feature in these cyclization processes. Kinetic experiments reveal that the gold activation mode is influenced by the ligand of the gold catalyst and the reaction conditions.     

Gold(I)‐Catalyzed Aminohalogenation of Fluorinated N′‐Aryl‐N‐Propargyl Amidines for the Synthesis of Imidazole Derivatives under Mild Conditions

A procedure for the synthesis of fluorinated imidazole derivatives from propargyl amidines has been developed. Under gold(I) catalysis, propargyl amidines were converted into 5‐fluoromethyl imidazoles in the presence of Selectfluor through a cascade cyclization/fluorination process. In contrast, imidazole‐5‐carbaldehydes were obtained in high yields when N‐iodosuccinimide (NIS) was used as the halogenating reagent. The polarity of the solvent and light had significant impact on the formation of the carbaldehydes. These transformations showed excellent functional‐group tolerance. An unfluorinated substrate with an electron‐withdrawing group also underwent aminohalogenation to give the corresponding product in good yield. Mechanistic investigation revealed the general pathways of these transformations.     

N‐Heterocyclic Carbene Gold(I) Catalyzed Transformation of N‐Tethered 1,5‐Bisallenes to 6,7‐Dimethylene‐3‐azabicyclo[3.1.1]heptanes

Tying up loose ends : The reaction of bisallenes tethered with N‐(p‐tolylsulfonamide) in the presence of a cationic gold N‐heterocyclic carbene catalyst gave new cycloisomerization products, 6,7‐dimethyleneazabicyclo[3.1.1]heptanes, in high yields (see scheme; IPr=N,N′‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene).

     

An Original L‐shape,Tunable N‐Heterocyclic Carbene Platform for Efficient Gold(I) Catalysis

The synthesis and characterization of original NHC ligands based on an imidazo[1,5‐a]pyridin‐3‐ylidene (IPy) scaffold functionalized with a flanking barbituric heterocycle is described as well as their use as tunable ligands for efficient gold‐catalyzed C?N, C?O, and C?C bond formations. High activity, regio‐, chemo‐, and stereoselectivities are obtained for hydroelementation and domino processes, underlining the excellent performance (TONs and TOFs) of these IPy‐based ligands in gold catalysis. The gold‐catalyzed domino reactions of 1,6‐enynes give rise to functionalized heterocycles in excellent isolated yields under mild conditions. The efficiency of the NHC gold 5^Me complex is remarkable and mostly arises from a combination of steric protection and stabilization of the cationic Au^I active species by ligand 1^Me .