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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.

[1,4]Oxazino[3,2-b]indoles as well as 1H-pyrazino[2,3-b]indoles are constructed in good to excellent yields via gold-catalyzed cascade cyclization of (azido)ynamides. The use of readily available starting materials, a simple procedure and mild reaction conditions are other significant features of this method.

An unprecedented gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles has been developed, allowing rapid and practical access to a wide range of synthetically useful 2-aminopyrroles., 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.

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 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, which provides a reliable access to synthetically useful 3-oxyindoles. Importantly, this gold-catalyzed oxidative process outcompetes the typical indole formation.

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.

We are grateful for the financial support from the National Natural Science Foundation of China (No. 21102119 and 21272191), the Natural Science Foundation of Fujian Province of China (No. 2012J01051), NFFTBS (No. J1210014), and PCSIRT. We also thank Professor Dr. Liming Zhang (University of California Santa Barbara) for the helpful discussions.

The presented cycloisomerization proceeds through an anti-Markovnikov addition by using a base in catalytic amount.

Formal [3 + 2] cycloaddition of various ynamides with isoxazoles results in the formation of a series of 2-aminopyrroles.

A simple procedure is elaborated for the gold-catalyzed synthesis of indole derivatives (III), (V), and (VII) from o-alkynyl anilines and ynamides.

A novel gold-catalyzed tandem cycloisomerization/dimerization of chiral homopropargyl sulfonamides is developed.