Chao Shu

Generation of α-Imino Gold Carbenes through Gold-Catalyzed Intermolecular Reaction of Azides with Ynamides

The generation of α-imino gold carbenes via gold-catalyzed intermolecular reaction of azides and ynamides is disclosed. This new methodology allows for highly regioselective access to valuable 2-aminoindoles and 3-amino-β-carbolines in generally good to excellent yields. A mechanistic rationale for this tandem reaction, especially for the observed high regioselectivity, is supported by DFT calculations.

Generation of gold carbenes in water: efficient intermolecular trapping of the α-oxo gold carbenoids by indoles and anilines

The efficient intermolecular reaction of gold carbene intermediates, generated via gold-catalyzed alkyne oxidation, with indoles and anilines has been realized in aqueous media. Importantly, it was revealed for the first time that water could dramatically suppress the undesired over-oxidation, providing a general and practical solution to the problem of over-oxidation in gold-catalyzed intermolecular alkyne oxidation with external nucleophiles. This strategy was successfully applied to the formal synthesis of the Pfizers chiral endothelin antagonist UK-350,926.

Zinc‐Catalyzed Alkyne Oxidation/CH Functionalization: Highly Site‐Selective Synthesis of Versatile Isoquinolones and β‐Carbolines

An efficient zinc(II)-catalyzed alkyne oxidation/C-H functionalization sequence was developed, thus leading to highly site-selective synthesis of a variety of isoquinolones and β-carbolines. Importantly, in contrast to the well-established gold-catalyzed intermolecular alkyne oxidation, over-oxidation can be completely suppressed in this system and the reaction most likely proceeds by a Friedel-Crafts-type pathway. Mechanistic studies and theoretical calculations are described.

Gold-Catalyzed Oxidative Cyclization of Chiral Homopropargyl Amides: Synthesis of Enantioenriched γ-Lactams

A gold-catalyzed tandem cycloisomerization/oxidation of homopropargyl amides has been developed, which provides ready access to synthetically useful chiral γ-lactams with excellent ee by combining the chiral tert-butylsulfinimine chemistry and gold catalysis. The utility of this methodology has also been demonstrated in the synthesis of biologically active compound S-MPP and natural product (-)-bgugaine. The use of readily available starting materials, a simple procedure, and mild reaction conditions are other significant features of this method.

Recent progress towards gold-catalyzed synthesis of N-containing tricyclic compounds based on ynamides

N-Containing tricyclic compounds, especially the tricyclic N-heterocycles, are important structural motifs that possess significant potential in organic chemistry for their momentous applications in natural and man-made bioactive molecules. Gold catalysis, which exhibits specific catalytic properties in terms of both high reactivity and selectivity for various organic transformations, has proven to be a powerful tool for the straightforward synthesis of cyclic compounds, especially the polycyclic molecules. Currently, several approaches towards polycycle synthesis have been developed via gold-catalyzed transformations of readily available ynamides. In this review, we will focus on the recent advances in the gold-catalyzed construction of N-containing tricycles based on ynamides by highlighting their specificity and applicability, and the mechanistic rationale is presented where possible.

Gold-Catalyzed Tandem Cycloisomerization/Functionalization of in Situ Generated α-Oxo Gold Carbenes in Water

A gold-catalyzed tandem cycloisomerization/functionalization of in situ generated α-oxo gold carbenes in water has been developed, which provides ready access to highly functionalized indole derivatives from o-alkynyl anilines and ynamides. Importantly, gold serves dual catalytic roles to mediate both the cycloisomerization of o-alkynyl anilines and the intermolecular oxidation of ynamides at the same time, thus providing a new type of concurrent tandem catalysis. The use of readily available starting materials, a simple procedure, and mild reaction conditions are other notable features of this method.

Gold-Catalyzed Intermolecular Ynamide Amination-Initiated Aza-Nazarov Cyclization: Access to Functionalized 2-Aminopyrroles

A novel gold-catalyzed intermolecular ynamide amination-initiated aza-Nazarov cyclization has been developed, allowing the facile and efficient synthesis of various 2-aminopyrroles in moderate to good yields. Furthermore, a mechanistic rationale for this tandem sequence, especially for the observed high regioselectivity, is also well supported by DFT (density functional theory) computations. The high flexibility, broad substrate scope, and mild nature of this reaction render it a viable alternative for the construction of 2-aminopyrroles.

Atom-Economic Synthesis of Fully Substituted 2-Aminopyrroles via Gold-Catalyzed Formal [3+2] Cycloaddition between Ynamides and Isoxazoles

A concise and flexible synthesis of fully substituted 2-aminopyrroles via gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles has been developed. Under mild reaction conditions, various 2-aminopyrrole derivatives were obtained in good to excellent yields, thus providing an efficient and atom-economic way for the construction of fully substituted 2-aminopyrroles.

Flexible and Practical Synthesis of Anthracenes through Gold-Catalyzed Cyclization of o-Alkynyldiarylmethanes

A concise gold-catalyzed method for the preparation of anthracenes from o-alkynyldiarylmethanes has been developed. Under mild reaction conditions, versatile anthracene derivatives were formed in moderate to good yields. The high flexibility, broad substrate scope, and mild nature of this reaction render it a viable alternative for the synthesis of anthracenes.

Practical, Modular, and General Synthesis of 3-Coumaranones through Gold-Catalyzed Intermolecular Alkyne Oxidation Strategy

A gold-catalyzed intermolecular alkyne oxidation for the preparation of 3-coumaranones has been developed. Using 8-isopropylquinoline N-oxides as oxidants, the reactions of o-ethynylanisoles afford versatile 3-coumaranones in moderate to good isolated yields. The synthetic utility of this chemistry is also indicated by the synthesis of the natural product sulfuretin.