Metal-Free Radical [3 + 2] Annulation of Tetraalkylthiuram Disulfide with Alkynes/Alkenes: An Approach of Synthesizing 1,3-Dithiole and 1,3-Ditholane Derivatives.

A novel and metal-free [3 + 2] annulation of tetraalkylthiuram disulfide with alkynes/alkenes has been developed using Selectfluor at room temperature. The formed 1,3-dithiol-2-ylium/1,3-dithiolan-2-ylium salts can be easily transformed into the corresponding 1,3-dithiol-2-ylidenes/1,3-ditholan-2-ylidenes by one-pot subsequent condensation with malononitrile. The present protocol features the use of easily accessible starting materials, mild reaction conditions, good tolerance with diverse functional groups, easy scale-up, and a wide substrate scope, affording the desired products in good yields. Importantly, this method is suitable for the late-stage modification of bioactive molecules. Furthermore, 1,3-dithiol-2-ylium salt can also be easily converted into various 1,3-dithiole derivatives by condensation, reduction, or hydrolysis. Mechanism studies show that this transformation involves radical annulation. Of note, this method presented a novel example using tetraalkylthiuram disulfide as a sulfur synthon in annulation, which greatly enriches the application of tetraalkylthiuram disulfides in organic synthesis. Biological evaluation indicates that these prepared compounds are promising candidates in terms of their antitumor activity.

Design, Synthesis, and Biological Evaluation of ß-Trifluoroethoxydimethyl Selenides as Potent Antiosteoporosis Agents.

An efficient protocol for the synthesis of ß-trifluoroethoxydimethyl selenides was achieved under mild reaction conditions, and 39 compounds were prepared. All compounds were evaluated for their abilities to inhibit RANKL-induced osteoclastogenesis, compound 4aa exhibited the most potent activity. Further investigations revealed that 4aa could inhibit F-actin ring generation, bone resorption, and osteoclast-specific gene expression in vitro. Western blot analyses demonstrated that compound 4aa abrogated the RANKL-induced mitogen-activated protein kinase and NF-kB-signaling pathways. In addition, 4aa also displayed a notable impact on the osteoblastogenesis of MC3T3-E1 preosteoblasts. In vivo experiments revealed that compound 4aa significantly ameliorated bone loss in an ovariectomized (OVX) mice model. Furthermore, the surface plasmon resonance experiment results revealed that 4aa probably bound to RANKL. Collectively, the above-mentioned findings suggested that compound 4aa as a potential RANKL inhibitor averted OVX-triggered osteoporosis by regulating the inhibition of osteoclast differentiation and stimulation of osteoblast differentiation.

Metal-Free Thiocarbamation of Quinolinones: Direct Access to 3,4-Difunctionalized Quinolines and Quinolinonyl Thiocarbamates at Room Temperature.

A novel and practical method for the preparation of difunctionalized quinolines, bearing a thiocarbamate group at the C3-position and an acyloxyl group at the C4-position, and quinolinonyl thiocarbamates from quinolinones, tetraalkylthiuram disulfides, and hypervalent iodine(III) reagents has been developed via thiocarbamation of quinolinones at room temperature. The present method features mild reaction conditions, good tolerance with diverse functional groups, and a wide substrate scope, providing the desired products in good yields. Furthermore, this transformation is easy to scale up, and the desired products can be readily converted to heterocyclic thiols. Most importantly, this protocol allows for the late-stage thiocarbamation of bioactive compounds. Mechanistic studies show that radicals may be involved in this transformation, water is probably the oxygen source of thiocarbamates, and difunctionalized quinolines are possibly formed via nucleophilic attack of carboxylic anions, which derive from hypervalent iodine(III) reagents.

C-H Diselenation and Monoselenation of Electron-Deficient Alkenes via Radical Coupling at Room Temperature.

A new, simple, and metal-free route for the diselenation of maleimides has been first developed employing (bis(trifluoroacetoxy)iodo)benzene (PIFA) at room temperature. The present method is compatible with different functional groups, and various diselenyl maleimides were obtained in moderate to excellent yields. Moreover, this protocol further highlights the unique practical application for the functionalization of biologically relevant molecules and amino acid derivatives. Preliminary mechanism studies suggest that radicals may be involved in this novel transformation. Additionally, this protocol is also applicable for the monoselenation of maleimides by switching the reaction conditions and selenation of other electron-deficient alkenes.

Regioselective peri-C-H selenylation of aromatic compounds with weakly coordinating ketone groups.

A novel and versatile method for peri-C-H selenylation of aromatic compounds bearing ketone groups, including chromones, xanthones, acridinones, quinolinones and naphthoquinones with diselenides under Ru(II) catalysis is presented. Various chromones and diselenides are applicable for this transformation, affording 5-selenyl chromones in a highly regioselective manner in good to excellent yields. This transformation is easy to scale up and the desired products can be further modified. Most importantly, this transformation allows the late-stage selenylation of bioactive compounds. Mechanistic studies show that radicals may be involved in this novel transformation.