Gold-catalyzed Annulation Research Articles

Highly Regio‐, Diastereo‐, and Enantioselective Gold(I)‐Catalyzed Intermolecular Annulations with N‐Allenamides at the Proximal CC Bond

A highly enantioselective gold(I)-catalyzed intermolecular annulation of 2-(1-alkynyl)-2-alken-1-ones with N-allenamides is presented. The present work represents the first example of a gold-catalyzed annulation with the proximal C=C bond of an N-allenamide, and is distinctly different from the previously observed annulations at the distal C=C bond. Interestingly, both enantiomers of the products could be obtained in good yields with high regio-, diastereo-, and enantioselectivity by using either diastereomer of a binol-derived phosphoramidite as a chiral ligand.

Enantioselective One-Pot Copper- and Gold-Catalyzed Alkylation and Annulation

Enantioselective One-Pot Copper- and Gold-Catalyzed Alkylation and Annulation

Gold as Catalyst for the Hydroarylation and Domino Hydroarylation/N1-C4 Cleavage of β-Lactam-Tethered Allenyl Indoles.

Gold-catalyzed hydroarylation reaction of β-lactam-tethered allenyl indoles gives azeto-oxepino[4,5-b]indol-2-ones, tetrahydroazeto-azocino[3,4-b]indol-2-ones, and hexahydroazeto-azepino[3,4-b]indol-2-ones with very high levels of stereo- and regioselectivity, the 7-exo and 8-endo carbocyclization modes by attack of the indole group toward either the internal or the terminal allene carbon, respectively, being favored. Hydroarylation across the central carbon of the allene moiety has not been detected. The controlled gold-catalyzed annulations allowed the formation of fused β-lactams without harming the sensitive four-membered heterocycle. Besides, a novel gold-catalyzed domino process, namely, the allenic hydroarylation/N1-C4 β-lactam bond breakage to afford dihydro-oxepino[4,5-b]indole-4-carboxamides, has been discovered.

Gold-catalyzed annulations of allenes with N-hydroxyanilines to form indole derivatives with benzaldehyde as a promoter

Gold-catalyzed syntheses of 2,3-disubstituted indole derivatives from N-hydroxyanilines and allenes are described; these reactions require benzaldehyde as an additive to generate nitrones in situ. Our control experiments indicate that nitrones and water were indispensable in the reactions whereas N-hydroxyanilines alone were inactive nucleophiles. This synthetic method is compatible with allenes and N-hydroxyanilines with a reasonable range, further highlighting its synthetic utility.

Development of a new class of aromatase inhibitors: Design, synthesis and inhibitory activity of 3-phenylchroman-4-one (isoflavanone) derivatives

Aromatase (CYP19) catalyzes the aromatization reaction of androgen substrates to estrogens, the last and rate-limiting step in estrogen biosynthesis. Inhibition of aromatase is a new and promising approach to treat hormone-dependent breast cancer. We present here the design and development of isoflavanone derivatives as potential aromatase inhibitors. Structural modifications were performed on the A and B rings of isoflavanones via microwave-assisted, gold-catalyzed annulation reactions of hydroxyaldehydes and alkynes. The in vitro aromatase inhibition of these compounds was determined by fluorescence-based assays utilizing recombinant human aromatase (baculovirus/insect cell-expressed). The compounds 3-(4-phenoxyphenyl)chroman-4-one (1h), 6-methoxy-3-phenylchroman-4-one (2a) and 3-(pyridin-3-yl)chroman-4-one (3b) exhibited potent inhibitory effects against aromatase with IC50 values of 2.4μM, 0.26μM and 5.8μM, respectively. Docking simulations were employed to investigate crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding and heme iron coordination. This report provides useful information on aromatase inhibition and serves as a starting point for the development of new flavonoid aromatase inhibitors.

Mechanism of the N-protecting group dependent annulations of 3-aryloxy alkynyl indoles under gold catalysis: a computational study

The mechanism of the gold-catalyzed annulations of 3-aryloxy alkynyl indoles developed by Tu et al. was studied by DFT calculations. It was found that both indole derivatives of electron-donating and electron-withdrawing protective groups would first undergo the 5-exo-dig cyclization simultaneously upon activation by cationic [PR(3)Au(+)] species. However, divergent reactivity of the resulting spirocyclic intermediate in competitive 1,2-alkenyl migration and nucleophilic water addition reactions towards C3 was predicted. When protected by electron-donating group, the 1,2-alkenyl migration occurs to generate a tricyclic intermediate, from which an aromatic Claisen rearrangement/nucleophilic addition sequence results in the observed 1,2-phenoxy migration. In case of electron-withdrawing group, the 1,2-alkenyl migration would be unfavorable. Instead, the nucleophilic addition of water oxygen to C3 is more facile, and leads to the hemiketal intermediate. The possible roles of water-cluster and OTf anion as proton shuttles in both reactions were also evaluated.

Au(I)‐Catalyzed Annulation of 2‐Tosylaminobenzaldehyde and Alkynes.

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Rapid syntheses of (±)-pterocarpans and isoflavones via the gold-catalyzed annulation of aldehydes and alkynes

(±)-Pterocarpan and analogues ( 4a– c) have been synthesized efficiently via the annulation of salicylaldehydes ( 1a, 1b and 1c) and o-methoxymethoxylphenylacetylene ( 2a), followed by a one-pot reduction and acidic cyclization of the ketones ( 3a– c). In addition, isoflavone derivatives ( 5a– c) have been synthesized rapidly, in two steps, via the annulation of salicylaldehyde ( 1a) and arylacetylenes ( 2b, 2c and 2d), followed by IBX/DMSO oxidation of the isoflavanones ( 3d, 3e and 3f).

Au(I)-Catalyzed Annulation of 2-Tosylaminobenzaldehyde and Alkynes

2,3-Dihydro-1-tosylquinolin-4(1H)-one derivatives, azaisoflavanones, have been synthesized efficiently via a gold-catalyzed annulation of 2-tosylaminobenzaldehyde and alkynes. This annulation offers the synthesis of a range of potentially bioactive molecules.