A concise and flexible synthesis of α,β-unsaturated amidines via gold-catalyzed intermolecular ynamide amination/carbene 1,2-shift between ynamides and benzylic azides has been developed. Under mild reaction conditions, various α,β-unsaturated amidines were obtained in mostly good yields, thus providing an efficient and atom-economic way for the construction of valuable α,β-unsaturated amidines.

An efficient yttrium-catalyzed tandem intermolecular hydroalkoxylation/Claisen rearrangement has been developed, providing various γ,δ-unsaturated amides in generally good to excellent yields. Importantly, high Z/E selectivity and diastereoselectivity were achieved. Other notable features of this method include widespread availability of the substrates, compatibility with a broad range of functional groups, and mild reaction conditions.

Ynamides are important building blocks in organic synthesis, and a variety of versatile synthetic methods have been developed in the past decade. Among these, catalytic cyclizations of π-tethered ynamides are particularly attractive, since this approach enables facile access to a diverse array of synthetically useful nitrogen heterocycles. However, due to the fact that the nitrogen atom is able to impose an electronic bias, these cyclizations exclusively occur on the α position of ynamides. Herein, we report the reversal of regioselectivity in arene-ynamide cyclization by copper catalysis, which represents the first catalytic π-tethered ynamide cyclization involving the reversal of regioselectivity. This strategy allows the expedient and practical synthesis of valuable azepino[4,5-b]indoles and β-carbolines in generally high yields under mild conditions. Moreover, the relevant mechanistic rationale for this cyclization, especially for the observed high regioselectivity, is strongly supported by density functional theory (DFT) calculations. The synthetic utility of this chemistry is also indicated by the synthesis of several biologically active compounds and natural product bauerine A.Keywords: copper; heterocycles; homogeneous catalysis; regioselectivity; synthetic methods;

A novel dual gold/photoredox-catalyzed bis-arylative cyclization of chiral homopropargyl sulfonamides with diazonium salts has been developed, allowing the facile synthesis of various enantioenriched 2,3-dihydropyrroles in generally moderate to good yields with excellent enantioselectivities under very mild conditions without using any strong oxidants. The reaction is proposed to undergo an AuI/AuIII redox cycle promoted by visible-light photoredox catalysis.

Isoxazoles, as masked 1,3-dicarbonyl equivalents, have proven to be versatile building blocks and pivotal intermediates for the construction of a variety of useful azacycles with molecular complexity. As a result, a range of new reactions have been discovered based on isoxazoles in the past decade. However, the relevant reactions of isoxazoles with alkynes have seldom been explored. In this review, we will focus on the recent progress in the transition-metal-catalyzed formal annulations for the efficient synthesis of N-heterocycles between alkynes and isoxazoles by highlighting their specificity and applicability, and the mechanistic rationale is presented where possible.

A novel copper-catalyzed N-oxide oxidation of N-sulfonyl ynamides is disclosed. This non-noble metal-catalyzed protocol enables facile and efficient access to valuable α-keto imides in generally good to excellent yields. Other notable features of this method include widespread availability of the substrates, compatibility with broad functional groups, a simple procedure, mild conditions, and in particular, no need to exclude moisture or air (“open flask”).

A Lewis acid-catalyzed alkyne oxidation strategy has been developed to produce diverse α-functionalized amides from readily and generally available ynamides. An efficient zinc(II)-catalyzed oxidative azidation and thiocyanation has been achieved, providing facile access to synthetically useful α-azido amides and α-thiocyanate amides, respectively. This chemistry can also be extended to oxidative halogenations by employing the 2-halopyridine N-oxide as both the oxidant and the halogen source, and its mechanistic rationale is also supported by density functional theory calculations. Moreover, NaBARF has been demonstrated to catalyze such an alkyne oxidation effectively, thus further excluding the metal carbene pathway in this cascade reaction.Keywords: alkyne; azidation; halogenation; homogeneous catalysis; oxidation; synthetic methods

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.

A novel gold-catalyzed tandem cycloisomerization/hydrogenation of chiral homopropargyl sulfonamides has been developed. Various enantioenriched pyrrolidines can be obtained in excellent yields and excellent enantioselectivities by combination of chiral tert-butylsulfinimine chemistry with gold catalysis. Importantly, this represents the first example of a pyrrolidine synthesis from homopropargyl sulfonamide.

A novel gold-catalyzed tandem intermolecular ynamide amination/C–H functionalization has been developed. A variety of highly functionalized 2-aza-1,3-butadienes can be obtained readily by utilizing this strategy. In addition, α-imino gold carbene intermediates are proposed in this amination reaction and with support by DFT (density functional theory) calculations.

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.

The generation of gold carbenes via the gold-catalyzed intermolecular reaction of nucleophiles containing relatively labile N–O or N–N bonds with alkynes has received considerable attention during recent years. However, this protocol is not atom-economic as the reaction produces a stoichiometric amount of pyridine or quinoline waste, the cleaved part of the N–O or N–N bonds. In this article, we disclose an unprecedented gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles, allowing rapid and practical access to a wide range of synthetically-useful 2-aminopyrroles. Most importantly, mechanistic studies and theoretical calculations revealed that this reaction presumably proceeds via an α-imino gold carbene pathway, thus providing a strategically novel, atom-economic route to the generation of gold carbenes. Other significant features of this approach include the use of readily-available starting materials, high flexibility, simple procedure, mild reaction conditions, and in particular, no need to exclude moisture or air (“open flask”).

A direct gold-catalyzed 5-endo-dig cycloisomerization of chiral homopropargyl sulfonamides has been developed. A range of enantioenriched 2,3-dihydropyrroles are readily accessed by utilizing this approach. Importantly, this gold-catalyzed cycloisomerization reaction proceeds through an anti-Markovnikov addition by using a catalytic base as the additive, which completely suppresses the undesired dimerization.

Over the past few decades, ylide chemistry has been significantly extended to an area beyond olefination and small ring formation, among which ylide [4 + 1] annulation has been extensively explored, and five-membered ring structures, such as dihydrofurans, isoxazolines, pyrrolines, indoles, dihydropyrazoles and cyclopentenones, can be readily constructed through this type of transformation. An overview of the recent advances in this field is presented herein. Ylide [4 + 1] annulations are reviewed by highlighting their product diversity, selectivity and applicability, and the mechanistic rationale is presented when possible.

Correction for ‘Ylide formal [4 + 1] annulation’ by Chunyin Zhu et al., Org. Biomol. Chem., 2015, 13, 2530–2536.

A novel zinc-catalyzed intermolecular oxidation of N-sulfonyl ynamides has been developed. A variety of functionalized α,β-unsaturated N-sulfonyl imides are readily accessed by utilizing this approach, thus providing a viable alternative to synthetically useful α,β-unsaturated imides. Importantly, the reaction is proposed to proceed by a vinyligous E2-type elimination pathway, but not metal carbene pathway.

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 Pfizer's chiral endothelin antagonist UK-350,926.

A novel gold-catalyzed intermolecular oxidation of o-ethynylanilines has been developed. A range of functionalized 3-oxyindoles are readily accessed by utilizing this strategy. Importantly, this gold-catalyzed oxidative process outcompetes the typical indole formation.

A novel gold-catalyzed intermolecular oxidation of o-alkynylbiaryls has been developed. A variety of functionalized fluorenes are readily accessed by utilizing this non-diazo approach, thus providing a viable alternative to synthetically useful fluorenes.

A gold-catalyzed intermolecular oxidation of chiral homopropargyl sulfonamides has been developed, which provides a reliable access to synthetically useful chiral pyrrolidin-3-ones with excellent ee, by combining the chiral tert-butylsulfinimine chemistry and gold catalysis. This methodology has also been used in the facile synthesis of natural product (−)-irniine. The use of readily available starting materials, a broad substrate scope, a simple procedure and the mild nature of this reaction render it a viable alternative for the synthesis of enantioenriched pyrrolidin-3-ones.

The occurrence of the γ-lactam unit in the framework of various biologically active compounds has greatly contributed to the design and development of new synthetic transformations to access this important structural motif. Among the numerous methods developed so far, those based on transition metal catalysis are of high value as they generally allow efficient and selective access to functionalized γ-lactams under rather mild reaction conditions. An overview of the recent advances in this field is presented herein. Metal-catalyzed processes are reviewed by highlighting their specificity and applicability, and the mechanistic rationale is presented where possible.

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.

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.

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.

A novel Au-catalyzed tandem cycloisomerization/oxidation of homopropargyl alcohols was developed. Various γ-lactones can be accessed readily by utilizing this strategy. Notably, the mechanism of this reaction is distinctively different from the related Ru-catalyzed reactions where the ruthenium vinylidene intermediate was proposed.

Gold-catalyzed nucleophilic addition to terminal alkynes has received considerable interest in the past decade, as this chemistry offers a highly efficient and regioselective way for CC, CH and CX bond formation. However, such a nucleophilic addition mainly involves a Markovnikov addition. In this short review, the recent progress of the gold-catalyzed 5-endo-dig cycloisomerization-initiated tandem reactions by utilizing the steric strain in ring formation to achieve an anti-Markovnikov regioselectivity was reviewed, including the scope of reactions, mechanism and synthetic applications.Download high-res image (133KB)Download full-size image

A direct gold-catalyzed 5-endo-dig cycloisomerization of chiral homopropargyl sulfonamides has been developed. A range of enantioenriched 2,3-dihydropyrroles are readily accessed by utilizing this approach. Importantly, this gold-catalyzed cycloisomerization reaction proceeds through an anti-Markovnikov addition by using a catalytic base as the additive, which completely suppresses the undesired dimerization.

A gold-catalyzed intermolecular oxidation of chiral homopropargyl sulfonamides has been developed, which provides a reliable access to synthetically useful chiral pyrrolidin-3-ones with excellent ee, by combining the chiral tert-butylsulfinimine chemistry and gold catalysis. This methodology has also been used in the facile synthesis of natural product (−)-irniine. The use of readily available starting materials, a broad substrate scope, a simple procedure and the mild nature of this reaction render it a viable alternative for the synthesis of enantioenriched pyrrolidin-3-ones.

A novel gold-catalyzed intermolecular oxidation of o-ethynylanilines has been developed. A range of functionalized 3-oxyindoles are readily accessed by utilizing this strategy. Importantly, this gold-catalyzed oxidative process outcompetes the typical indole formation.

A novel gold-catalyzed intermolecular oxidation of o-alkynylbiaryls has been developed. A variety of functionalized fluorenes are readily accessed by utilizing this non-diazo approach, thus providing a viable alternative to synthetically useful fluorenes.

The generation of gold carbenes via the gold-catalyzed intermolecular reaction of nucleophiles containing relatively labile N–O or N–N bonds with alkynes has received considerable attention during recent years. However, this protocol is not atom-economic as the reaction produces a stoichiometric amount of pyridine or quinoline waste, the cleaved part of the N–O or N–N bonds. In this article, we disclose an unprecedented gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles, allowing rapid and practical access to a wide range of synthetically-useful 2-aminopyrroles. Most importantly, mechanistic studies and theoretical calculations revealed that this reaction presumably proceeds via an α-imino gold carbene pathway, thus providing a strategically novel, atom-economic route to the generation of gold carbenes. Other significant features of this approach include the use of readily-available starting materials, high flexibility, simple procedure, mild reaction conditions, and in particular, no need to exclude moisture or air (“open flask”).

Over the past few decades, ylide chemistry has been significantly extended to an area beyond olefination and small ring formation, among which ylide [4 + 1] annulation has been extensively explored, and five-membered ring structures, such as dihydrofurans, isoxazolines, pyrrolines, indoles, dihydropyrazoles and cyclopentenones, can be readily constructed through this type of transformation. An overview of the recent advances in this field is presented herein. Ylide [4 + 1] annulations are reviewed by highlighting their product diversity, selectivity and applicability, and the mechanistic rationale is presented when possible.

Correction for ‘Ylide formal [4 + 1] annulation’ by Chunyin Zhu et al., Org. Biomol. Chem., 2015, 13, 2530–2536.

The occurrence of the γ-lactam unit in the framework of various biologically active compounds has greatly contributed to the design and development of new synthetic transformations to access this important structural motif. Among the numerous methods developed so far, those based on transition metal catalysis are of high value as they generally allow efficient and selective access to functionalized γ-lactams under rather mild reaction conditions. An overview of the recent advances in this field is presented herein. Metal-catalyzed processes are reviewed by highlighting their specificity and applicability, and the mechanistic rationale is presented where possible.

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.

A novel dual gold/photoredox-catalyzed bis-arylative cyclization of chiral homopropargyl sulfonamides with diazonium salts has been developed, allowing the facile synthesis of various enantioenriched 2,3-dihydropyrroles in generally moderate to good yields with excellent enantioselectivities under very mild conditions without using any strong oxidants. The reaction is proposed to undergo an AuI/AuIII redox cycle promoted by visible-light photoredox catalysis.

A novel gold-catalyzed tandem alkyne amination/intramolecular O–H insertion has been developed. A variety of [1,4]oxazino[3,2-c]isoquinolines are readily accessed under mild reaction conditions by utilizing this strategy, thereby providing an efficient and practical route for the construction of synthetically useful fused isoquinolines.

A zinc-catalyzed oxidative reaction of ynamides with phenols and thiophenols under mild reaction conditions has been developed, which provides various α-aryloxy amides and α-arylthio amides in moderate to good yields, respectively. Importantly, high chemoselectivity is achieved by such a non-noble metal-catalyzed alkyne oxidation.

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 Pfizer's chiral endothelin antagonist UK-350,926.