An expedient and reliable method for accessing reactive alpha-oxo gold carbenes via gold-catalyzed intermolecular oxidation of terminal alkynes has been developed. Significantly, this method offers a safe and economical alternative to the strategies based on diazo substrates. Its synthetic potential is demonstrated by expedient preparation of dihydrofuran-3-ones containing a broad range of functional groups.

Facile cycloisomerization of (2-ethynylphenyl)alkynes is proposed to be promoted synergistically by two molecules of BrettPhosAuNTf2, affording tricyclic indenes in mostly good yields. A gold vinylidene is most likely generated as one of the reaction intermediates based on both mechanistic studies and theoretical calculations. Different from the well-known Rh, Ru and W counterparts, this novel gold species is highly reactive and undergoes facile intramolecular C(sp3)-H insertions as well as O-H and N-H insertions. The formation step for the gold vinylidene is predicted theoretically to be complex with a bifurcated reaction pathway. The pyridine N-oxide acts as a weak base to facilitate the formation of an alkynylgold intermediate, and the bulky BrettPhos ligand in the gold catalyst likely plays a role in sterically steering the reaction toward the gold vinylidene formation.

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.

Catalytic transformations involving metal carbenes are considered one of the most important aspects of homogeneous transition metal catalysis. Recently, gold-catalyzed generation of gold carbenes from readily available alkynes represents a significant advance in metal carbene chemistry. This Review summarizes the advances in the gold-catalyzed nitrene-transfer reactions of alkynes with nitrogen-transfer reagents, such as azides, nitrogen ylides, isoxazoles, and anthranils, and gold-catalyzed carbene-transfer reactions, involving oxygen atom-transfer reactions of alkynes with nitro compounds, nitrones, sulfoxides, and pyridine N-oxides, through the presumable α-imino gold carbene and α-oxo gold carbene intermediates, respectively. Gold-catalyzed processes are reviewed by highlighting their product diversity, selectivity, and applicability, and the mechanistic rationale is presented where possible.

A general solution for the synthesis of various oxetan-3-ones is developed. This reaction uses readily available propargylic alcohols as substrates and proceeds without the exclusion of moisture or air ('open flask'). Notably, oxetan-3-one, a highly valuable substrate for drug discovery, can be prepared in one-step from propargyl alcohol in a fairly good yield. The facile formation of the strained oxetane ring provides strong support for the intermediacy of α-oxo gold carbenes. This safe and efficient generation of gold carbenes via intermolecular alkyne oxidation offers a potentially general entry into α-oxo metal carbene chemistry without using hazardous diazo ketones.Oxetan-3-ones1 contain a strained four-membered ring and possess considerable synthetic/ medicinal utility. They have been incorporated into steroid skeletons,2 used to prepare oxetanocin derivatives,3 and converted into 3-aminooxetanes4 including 3-aminooxetane-3-carboxylic acid.4a Moreover, Rogers-Evans, Carreira and co-workers have shown that the oxetane ring can serve as a surrogate of a gem-dimethyl group,5a resemble a carbonyl group,5b and offer alternatives to 1,3-heteroatom-substituted cyclohexanes in spirocyclic structures5c in drug discovery; in these studies, the parent oxetan-3-one serves as an essential starting material for introducing the oxetane ring. However, synthesis of oxetan-3-ones typically demand multiple synthetic steps and/or highly functionalized substrates.1 For example, oxetan-3-one itself was prepared in 45a or 54 steps with 23% or 13% overall yield, respectively, highlighting the challenge of constructing this strained skeleton and the lack of efficient preparative methods.α-Diazo ketones have been used to prepare oxetan-3-ones (Scheme 1),6 but those diazo substrates are in general hazardous and their preparations are non-trivial. We have recently developed a practical and efficient synthesis of dihydrofuran-3-ones via gold-catalyzed intermolecular oxidation of terminal alkynes,7 where a C-C triple bond is converted into a reactive α-oxo gold carbene intermediate in the proposed catalytic cycle. This strategy would render alkynes equivalent to α-diazo ketones in accessing α-oxo metal carbene chemistry,8 which could offer significant synthetic and economic benefits. We speculated * zhang@chem.ucsb.edu . Supporting Information Available:Experimental procedures, compound characterization data. This material is available free of charge via the Internet at http://pubs.acs.org. that this equivalency could substitute the α-diazo ketone moiety in oxetan-3-one synthesis6 with a simple C-C triple bond (Scheme 1); as a result, readily available propargylic alcohols could serve as direct substrates. Herein, we report a successful implementation of the design and the development of a practical solution to oxetan-3-one synthesis; moreover, the ease of forming this strained ring provides convincing support for the formation of α-oxo gold carbene intermediates via intermolecular alkyne oxidation. NIH Public AccessPropargylic...

Small ring made easy and chiral Chiral azetidin-3-ones could be easily prepared from chiral N-propargylsulfonamides, which in turn are readily accessible in excellent e.e. via chiral sulfinamide chemistry. Using t-butanesulfonyl as the protecting group avoids unnecessary deprotection and reprotection and allows its removal from the azetidine ring under acidic conditions.

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.

Ynamides are special alkynes bearing an electron-withdrawing group on the nitrogen atom, and they have been extensively studied over the past decade. However, the addition of functional groups across ynamides in these transformations typically occurs at the α-position of the ynamide because of the strong polarization of the alkynyl moiety. Studies of umpolung transformations in ynamide chemistry may not only discover organic reactions but also lead to divergent organic syntheses, thus significantly enriching ynamide chemistry. This review summarizes four main strategies utilized to achieve reversal of the regioselectivity, including the ring strain factor, metal–carbonyl (or sulfonyl) chelation, and base-mediated and radical-initiated addition.