Rai-Shung Liu

Gold-Catalyzed Oxidative Cyclization of 1,5-Enynes Using External Oxidants**

Pd-catalyzed oxidative cyclizations of 1,6-enynes have found useful applications in organic synthesis, but such reactions with Au and Pt catalysis remain largely unexplored. Goldcatalyzed cycloisomerizations of 1,5and 1,6-enynes provide uncommon and useful carbocyclic frameworks. In the presence of organic oxidants, most enynes fail to produce oxidative cyclization products because oxidations of hypothetical gold–carbenoid intermediates are difficult. 5] Herein, we report two new oxidative cyclizations of 1,5-enynes via 5endo-dig and 5-exo-dig cyclizations, respectively; both reactions are implemented with Au and 8-methylquinoline Noxide. The success of such reactions relies on the prior oxidations of enyne form a-carbonyl carbenoids A and B, followed by their intramolecular cyclizations (Scheme 1). Terminal alkynes favor the oxidation at the C2 alkynyl carbon atom and aminoalkynes prefer the C1 carbon atom.

Gold-Catalyzed Oxidative Ring Expansions and Ring Cleavages of Alkynylcyclopropanes by Intermolecular Reactions Oxidized by Diphenylsulfoxide†

Cyclobutane derivatives are important structural units in many natural products, but efficient methods for their synthesis are few compared to those for the preparation of other carbocyclic systems. An advance in the synthesis of cyclobutane derivatives involves metal-catalyzed ring-expansions of cyclopropane derivatives, including alkylidenecyclopropanes, allenylcyclopropanols or alkynylcyclopropanols, with selected examples depicted in Scheme 1. Such

Gold-Catalyzed Formal [3 + 3] and [4 + 2] Cycloaddition Reactions of Nitrosobenzenes with Alkenylgold Carbenoids

We report two new formal cycloaddition reactions between nitrosobenzenes and alkenylgold carbenoids. We obtained quinoline oxides 3 in satisfactory yields from the gold-catalyzed [3 + 3]-cycloadditions between nitrosobenzenes and alkenyldiazo esters 1. For propargyl esters 5, its resulting gold carbenes react with nitrosobenzene to give alkenylimine 8, followed by a [4 + 2]-cycloaddition with nitrosobenzene.

Gold-Catalyzed 1,2-Difunctionalizations of Aminoalkynes Using Only N- and O-Containing Oxidants

We report two viable routes for the 1,2-difunctionalization of aminoalkynes using only oxidants. In the presence of a gold catalyst, nitrones enable the oxoamination of aminoalkynes 1 to form 2-aminoamides 2. With a suitable gold catalyst, nitrosobenzenes implement an alkyne/nitroso metathesis of the same substrates to give 2-oxoiminylamides 3. These two novel oxidations also provide 1,2-aminoalcohols with opposite regioselectivity via NaBH(4) reduction in situ.

Gold-catalyzed oxidative cyclizations of cis-3-en-1-ynes to form cyclopentenone derivatives.

the corresponding oxidative cyclizationremains undocumented. Herein, we report new gold-cata-lyzed oxidative cyclizations of cis-3-en-1-ynes to give cyclo-pentenone skeletons using 8-methylquinoline oxide (Sche-me 1b). Notably, the mechanistic transformation of this C Hactivation is proven to proceed through a noncarbene route,thus excluding the intermediacy of the a-carbonyl carbeneA.

Diversity in gold- and silver-catalyzed cycloisomerization of epoxide-alkyne functionalities.

We report Au(I)- and Ag(I)-catalyzed cycloisomerizations of epoxide-alkyne functionalities in both aromatic and nonaromatic systems, leading to diversified carbocyclic and heterocyclic frameworks with high chemoselectivities. The use of such cycloisomerizations is reflected by a facile access to the cores of natural pallidol and gibberic acid.

Gold-Catalyzed Intermolecular [4+2] and [2+2+2] Cycloadditions of Ynamides with Alkenes†

Gold-catalyzed cycloisomerizations of 1,5and 1,6-enynes represent important advances in modern catalysis. These reactions provide unusual and diverse carbocyclic compounds that are not readily synthesized by common methods. Importantly, such cycloisomerizations allow facile access to naturally occurring compounds. As gold-catalyzed enyne cycloisomerizations occur exclusively under intramolecular conditions, little effort has been devoted to the study of intermolecular reactions between alkynes and alkenes. 5] Hashmi et al. studied the gold-catalyzed reaction of phenylacetylene with excess 2,5-furan, which gave the desired 2phenyl-3,5-dimethylphenol in a low yield (Scheme 1). Very recently, Echavarren and co-workers reported the efficient synthesis of cyclobutene derivatives by gold-catalyzed intermolecular [2+2] cycloadditions of phenylacetylenes with alkenes. Intermolecular reactions of alkynes with alkenes can also be performed with nickel and cobalt complexes to give acyclic butene or butadiene derivatives. We investigated new intermolecular reactions of alkynes with alkenes catalyzed by gold complexes. Herein, we report [4+2] cycloadditions of 2-arylynamides with alkenes, and [2+2+2] cycloadditions of arylynamides with enol ethers (Scheme 1). To our knowledge, there are no analogous interor intramolecular reactions for this type of [2+2+2] cycloaddition. Recently, there has been considerable interest in the electrophilic activation of ynamides and alkynyl ethers. Such substrates are studied because they are more electrophilic than other, more common alkynes in reactions catalyzed by gold compounds. These effects arise from the polarized palkyne character of the substrate–catalyst complex (I, which can also be drawn as the ketene resonance structure (II), Scheme 2) and can control the regioselectivity of reactions.

Gold-Catalyzed Stereoselective Synthesis of Azacyclic Compounds through a Redox/[2 + 2 + 1] Cycloaddition Cascade of Nitroalkyne Substrates

We report a new redox/cycloaddition cascade on readily available 1-alkynyl-2-nitrobenzenes that produces complex azacyclic compounds stereoselectively. The core structures of the resulting products are constructed through a formal [2 + 2 + 1] cycloaddition among α-carbonyl carbenoids, nitroso species, and external alkenes.

Gold‐Catalyzed Formal Cycloaddition of 2‐Ethynylbenzyl Ethers with Organic Oxides and α‐Diazoesters

A world of possibilities: Gold-catalyzed reactions of 2-ethynylbenzyl ethers with organic oxides and α-diazoesters gave 1,3-dihydroisobenzofuran and naphthalene derivatives, respectively (see scheme; EWG = electron-withdrawing group). Mechanisms for the formation of the formal cycloadducts were elucidated by isotope labeling.

Regiocontrolled Gold‐Catalyzed [2+2+2] Cycloadditions of Ynamides with Two Discrete Nitriles to Construct 4‐Aminopyrimidine Cores

Reported herein is the novel gold-catalyzed intermolecular [2+2+2] cycloaddition of ynamides with two discrete nitriles to form monomeric 4-aminopyrimidines, which are pharmaceutically important structural motifs. The utility of this new cycloaddition is demonstrated by the excellent regioselectivity obtained using a variety of ynamides and nitriles.