Iron Catalysis of C(sp3)-H Azidation Using a Heteroarene Radical Cation Strategy.

The FeIII(phen)3 catalysis of the benzylic C(sp3)-H azidation of indoles has been investigated. The Fe(III) complex can selectively oxidize indoles to form arene radical cations, which are transformed into benzylic C(sp3) radical intermediates. This strategy exhibits a difference in reactivity between N-heteroarenes and benzene, which is difficult to achieve via direct hydrogen abstraction approaches. Various biorelevant azide precursors were constructed, highlighting the utility of this mild first-row transition-metal catalyst system.

2,3-Difunctionalized Benzo[b]thiophene Scaffolds Possessing Potent Antiangiogenic Properties.

A new class of 2-anilino-3-cyanobenzo[b]thiophenes (2,3-ACBTs) was studied for its antiangiogenic activity for the first time. One of the 2,3-ACBTs inhibited tubulogenesis in a dose-dependent manner without any toxicity. The 2,3-ACBTs significantly reduced neovascularization in both ex vivo and in vivo angiogenic assays without affecting the proliferation of endothelial cells. Neovascularization was limited through reduced phosphorylation of Akt/Src and depolymerization of f-actin and ß-tubulin filaments, resulting in reduced migration of cells. In addition, the 2,3-ACBT compound disrupted the preformed angiogenic tubules, and docking/competitive binding studies showed that it binds to VEGFR2. Compound 2,3-ACBT had good stability and intramuscular profile, translating in suppressing the tumor angiogenesis induced in a xenograft model. Overall, the present study suggests that 2,3-ACBT arrests angiogenesis by regulating the Akt/Src signaling pathway and deranging cytoskeletal filaments of endothelial cells.

Triflic acid-mediated N-heteroannulation of ß-anilino-ß-(methylthio)acrylonitriles: a facile synthesis of 4-amino-2-(methylthio)quinolines.

Various functionalised 4-amino-2-(methylthio)quinolines are synthesised through triflic acid-mediated N-heteroannulation of α-functionalized-ß-anilino-ß-(methylthio)acrylonitriles for the first time. The N-heteroannulation process is highly chemoselective and has mild reaction conditions. However, this process fails in the absence of the ß-methylthio group in the acrylonitriles. In addition, a new double N-heteroannulation process is demonstrated to synthesise indolo[3,2-c]quinolines from non-heterocyclic precursors. Natural product isocryptolepine is synthesised in four steps from an acyclic precursor.

Chemoselective Ullmann Reaction of α-Trisubstituted Thioamides: Synthesis of Novel 2-Iminobenzothiolanes.

New classes of unexplored benzo[b]thiolanes are synthesized from trisubstituted thioamides through copper-catalyzed intramolecular S-arylation of thioamides for the first time. This method provides good to excellent yields with fully controlled chemoselectivity. Unusually, iminobenzo[b]thiolanes are very stable under mild acidic conditions. A plausible mechanism is proposed for the chemoselective S-arylation process.

Nickel catalyzed site selective C-H functionalization of α-aryl-thioamides.

A catalytic site selective intramolecular C-S bond forming reaction is demonstrated for the first time. The C-H bond functionalization of α-aryl-thioacetanilides was efficiently catalyzed by 2 mol% NiBr2, resulting in valuable 2-aminobenzo[b]thiophenes in moderate to good yields. Furthermore, the selective sp2 C-H bond functionalization over sp3 is exemplified.

Copper Catalyzed Intramolecular N-Arylation of Ketene Aminals at Room Temperature: Synthesis of 2-Amino-3-cyanoindoles.

Various 2-amino-3-cyanoindoles are synthesized through copper catalyzed intramolecular N-arylations of ketene aminals at room temperature for the first time with 60-99% yields within 0.1-2 h. Controlled regioselective N-arylations of unsymmetrical ketene aminals are also studied. Further, a new double heteroannulation approach is demonstrated for the synthesis of 11-aminoindolo[2,3- b]quinolines from acyclic and nonheterocyclic precursors.

Chemoselective Ullmann coupling at room temperature: a facile access to 2-aminobenzo[b]thiophenes.

Various functionalized 2-aminobenzo[b]thiophenes have been synthesized at room temperature by the Ullmann coupling reaction for the first time. The enantiospecific coupling reaction has been further demonstrated without loss of optical purity. The newly synthesized 2-anilino-3-cyano-benzo[b]thiophenes are transformed into 11-amino-benzothieno[2,3-b]quinolines in the presence of triflic acid.