Intermolecular Diastereoselective Annulation of Azaarenes into Fused N-heterocycles by Ru(II) Reductive Catalysis

Despite the important advances in azaaryl C−H activation/functionalization, reductive functionalization of ubiquitously distributed but weakly reactive azaarenes remains to date a challenge. Herein, by a strategy incorporating a tandem coupling sequence into the reduction of azaarenes, we present a dearomative annulation of azaarenes into promising fused syn-N-heterocycles by combination with a large variety of aniline derivatives and paraformaldehyde under ruthenium(II) reductive catalysis, proceeding with excellent selectivity, mild conditions, and broad substrate and functional group compatibility. Mechanistic studies reveal that the products are formed via hydride transfer-initiated β-aminomethylation and α-arylation of the pyridyl core in azaarenes, paraformaldehyde serves as both the C1-building block and reductant precursor, and the use of Mg(OMe)2 base plays a critical role in determining the reaction chemo-selectivity by lowering the hydrogen transfer rate. The present work opens a door to further develop valuable reductive functionalization of unsaturated systems by taking profit of formaldehyde-endowed two functions.

Copper-catalyzed ultrasonic-promoted coupling of acetylene analogs, dialkyl azo dicarboxylate, and benzazoles to assemble tricyclic fused-ring [1,2,3]triazolo[3,4-b][1,3]benzazole analogs

: An unprecedented copper-catalyzed reaction of acetylene analogs with dialkyl azo dicarboxylate and benzazole analogs via a cross-coupling sequence was reported. A library of triazolobenzazole fused ring systems including [1,2,3]triazolo[3,4-b][1,3]benzothiazole, [1,2,3]triazolo[3,4-b][1,3]benzoxazole and [1,2,3]triazolo[3,4-b][1,3]benzimidazole structures were obtained in moderate to excellent yields under very mild reaction conditions. Structural confirmation of the final products became possible using different methods like spectroscopy and elemental analysis. The control experiments indicated C-H activation of acetylene by copper salts, followed by cycloaddition between a 2-(phenylethynyl)benzo[d]azol-3(2H)-yl anion and azo dicarboxylate as the key mechanistic feature. The broad substrate scope with simple and easily-affordable starting materials as well as mild reaction conditions are the noticeable attributes of this methodology which provides facile access to the desired products.

Domino Heck/Hiyama cross-coupling: trapping of the σ-alkylpalladium intermediate with arylsilanes

A Pd-catalyzed domino Heck cyclization/Hiyama cross-coupling sequence of aryl-tethered activated/unactivated alkenes with arylsilanes is described.

Concise Synthesis of 1,1-Diarylvinyl Sulfones and Investigations on their Antiproliferative Activity via Tubulin Inhibition

Background: Discovery of small molecules that inhibit tubulin polymerization is an attractive strategy for the development of new and improved anti-proliferative agents. Objective: A series of novel 2-sulfonyl-1,1-diarylethenes were designed towards this end keeping in view the favorable chemical and pharmacological virtues of unsaturated sulfones. Methods: Rapid, convenient and efficient two-step assembly of the designed molecules was achieved by the vicinal iodo-sulfonylation-Suzuki coupling sequence. Results: As hypothesized, these compounds showed good anti-proliferative activity against different tissuespecific cancer cell lines: MCF-7, DU-145, A-549, HepG2, and HeLa. The most active compound, pnitrophenyl ring-bearing analog, exhibited an IC50 value of 0.90μM against A-549 cells. Flow cytometry studies on this derivative revealed that it arrests the cell cycle of A-549 cells at the G2/M phase. This compound exhibited molecular binding to tubulin as well as tubulin polymerization inhibition comparable to that of colchicine. Conclusion: A new class of potent, tubulin binding anticancer agents based on 1,1,-diarylvinyl sulfone scaffold has been designed and synthesized.

Indium-mediated difunctionalization of iodoalkyl-tethered unactivated alkenes via an intramolecular cyclization and an ensuing palladium-catalyzed cross-coupling reaction with aryl halides

A cobalt-catalyzed, indium-mediated difunctionalization of iodoalkyl-tethered unactivated alkenes for accessing five-membered cyclic compounds via a cyclization/cross-coupling sequence was developed.

para-Selective arylation and alkenylation of monosubstituted arenes using thianthrene S-oxide as a transient mediator

Using thianthrene S-oxide (TTSO) as a transient mediator, para-arylation and alkenylation of mono-substituted arenes have been demonstrated via a para-selective thianthrenation/Pd-catalyzed thio-Suzuki–Miyaura coupling sequence under mild conditions.