KOH-Mediated Synthesis of Substituted Isothiazoles via Two-Component Annulation with Dithioate and Aryl Acetonitrile.

We report a simple synthetic method for obtaining 3-hydroxy-4,5-disubstituted isothiazoles utilizing dithioester and aryl acetonitrile. The isothiazoles obtained in this method involve the formation of new C-C, C-O, and N-S bonds in one step using a simple base such as KOH under aerial conditions. The 3-hydroxy-4,5-disubstituted isothiazole was successfully employed for further functionalization.

Unexpected dearomatization of -protected 5-aminopyrazoles at ambient temperature: a simple route to highly functionalized pyrazolines.

We present a new strategy for the dearomatized hydroxylation of 5-aminopyrazoles using a hypervalent iodine reagent at room temperature. This method produces a series of 4-hydroxy-5-iminopyrazolines with good to excellent yields within 2 hours. Additionally, we demonstrate a domino reaction for the synthesis of 4-hydroxy-pyrazolones.

Organocatalytic Dearomatization of 5-Aminopyrazoles: Synthesis of 4-Hydroxypyrazolines.

Dearomatization is a fundamental chemical reaction that affords complex three-dimensional heterocyclic frameworks. We disclose the first organocatalytic dearomatization of 5-aminopyrazoles, which yields a range of structurally diversified C4-hydroxylated pyrazolines with yields of ≤95% in <1.5 h at room temperature.

PIFA-mediated intramolecular -arylation of 2-aminoquinoxalines to afford indolo[2,3-]quinoxaline derivatives.

We present the PIFA-mediated intramolecular -arylation of 2-aminoquinoxalines at room temperature for the first time. This method provides a wide range of indolo[2,3-]quinoxalines in good to excellent yields within a short time. The C-H bond functionalization occurs without the need for an inert atmosphere or additives.

Nickel Catalyzed Selective Arylation of Geminal Dinitriles: Direct Access to α-Cyano Carbonyl Compounds.

The catalytic intermolecular arylation of disubstituted geminal dinitriles with generated arylnickel complexes is disclosed. This method efficiently provides various all-carbon substituted α-cyanocarbonyl compounds without additives and an inert atmosphere. It also demonstrates the arylation of -BINOL and -BINOL derived geminal dinitriles, preserving optical purity.

Nickel-Catalyzed Domino Reaction of α-Aryloxyacetonitriles with Arylboronic Acids: Synthesis of 2-Aroylbenzo[]furans.

We disclose the first catalytic domino reaction of α-(2-formylaryloxy)acetonitriles with arylboronic acids, yielding a range of 2-aroylbenzo[]furans with yields of up to 93%. Ni(acac) serves as an effective dual catalyst. The protocol is also applicable to α-(2-acetylphenoxy)acetonitrile, giving rise to 3-methyl-2-aroylbenzo[]furans.

Cu(OTf) Enhanced Intramolecular Nucleophilic -Arylation of 2-Amino-3-arylquinolines.

In the presence of Cu(OTf) (5 mol %) and KOBu, a synergistic effect of the -arylation process on 2-amino-3-arylquinolines is observed. Within 4 h, this method provides a wide variety of norneocryptolepine analogues with good to excellent yields. Overall, a double heteroannulation strategy for the synthesis of indoloquinoline alkaloids from nonheterocyclic precursors is demonstrated.

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

A new class of 2-anilino-3-cyanobenzo[]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 and angiogenic assays without affecting the proliferation of endothelial cells.

Triflic acid-mediated N-heteroannulation of β-anilino-β-(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-β-anilino-β-(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 β-methylthio group in the acrylonitriles.

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

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

Paracetamol and other acetanilide analogs as inter-molecular hydrogen bonding assisted diamagnetic CEST MRI contrast agents.

Paracetamol and a few other acetanilide derivatives are reported as a special class of diamagnetic Chemical Exchange Saturation Transfer (diaCEST) MRI contrast agents, that exhibit contrast only when the molecules form inter-molecular hydrogen bonding mediated molecular chains or sheets. Without the protection of the hydrogen bonding their contrast producing labile proton exchanges too quickly with the solvent to produce any appreciable contrast. Through a number of variable temperature experiments we demonstrate that under the conditions when the hydrogen bond network breaks and the high exchange returns back, the contrast drops quickly.

PtCl mediated peripheral transformation of carbatriphyrin(3.1.1) into a -fused β-β' dimer and its monomer analogue.

An unprecedented formation of a meso-fused β-β' carbaporphyrin dimer and its monomer with a keto group was described. These analogues were synthesized from carbatriphyrin(3.1.

Copper-catalysed -arylation of 5-aminopyrazoles: a simple route to pyrazolo[3,4-]indoles.

A copper-catalysed intramolecular N-arylation of 5-aminopyrazoles is demonstrated for the first time. Highly substituted pyrazolo[3,4-b]indoles are synthesized. In particular, the indole core is decorated with halogens and alkyl and methoxy groups.

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.

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.

Double heteroannulation of S,N-acetals: a facile access to quinolone derivatives.

A rapid construction of quinolone fused heterocycles from single S,N-acetal precursors via double heteroannulation is described. The base, radical and metal-mediated reactions can control the C-N, C-S and C-O bond formations of the S,N-acetal with high chemoselectivity.

Catalytic selective deuteration of halo(hetero)arenes.

Deuterium labeled aromatic and heteroaromatic compounds are synthesized in good to excellent yields with >98% deuterium purity via palladium catalyzed deuterodehalogenation reaction using commercially available and inexpensive reagents. Selective deuteration of bromoaniline is also demonstrated without H/D exchange in an amino N-H group.

AIEE phenomenon: tetraaryl vs. triaryl pyrazoles.

Tetraarylpyrazoles are synthesized from commercially available materials in three steps and found to exhibit Aggregation Induced Emission Enhancement (AIEE) characteristics. Removing one aryl unit from tetraarylpyrazole leads to Aggregation Caused Quenching (ACQ), thus the number of aryl groups plays an important role in exploring such a phenomenon.

The Ti-BINOLate-catalyzed, enantioselective ring-opening of meso-aziridines with amines.

The titanium-BINOLate-catalyzed, highly enantioselective ring-opening reaction of meso-aziridines has been developed which furnishes trans-1,2-diamines in typically good yields and excellent enantioselectivities. N-Aryl aziridines attached to a 5- or 6-membered carbocyclic ring are among the best substrates for this process providing the products in up to >99% ee. The chiral catalyst is easily prepared in situ from commercially available components and does not require any laborious ligand synthesis.

Titanium binolate catalyzed aminolysis of meso aziridines: a highly enantioselective and direct access to 1,2-diamines.

It's as simple as that: An in situ prepared chiral catalyst from the commercially available compounds Ti(OiPr)(4) and (R)-binol catalyzes the highly enantioselective ring-opening of meso-aziridines 1 with anilines 2 and furnishes valuable chiral 1,2-diamines 3 in high yields and up to 99 % ee.(R)-binol=(R)-2,2'-dihydroxy-1,1'-binaphthyl.

A novel anionic domino process for the synthesis of o-cyanoaryl-methylthio/alkyl/aryl/heteroaryl acetylenes.

A novel unexpected anionic domino process involving n-BuLi-induced rearrangement of 3,3-bis(methylthio) or 3-methylthio-3-aryl/heteroaryl/alkyl-o-bromoarylacrylonitriles to o-cyanoarylacetylenes in synthetically useful yields has been reported. The scope and generality of the reaction has been examined, and a possible mechanism has been proposed.

Domino carbocationic rearrangement of alpha-[bis(methylthio)methylene]alkyl-2-(3/2-indolyl) cyclopropyl ketones.

Domino carbocationic rearrangement of a number of substituted 3- and 2-indolylcyclopropyl ketones with an alpha-bis(methylthio)methylene group in the presence of various protic/Lewis acids yields a variety of products, mainly the pentaleno fused indoles and the carbazole derivatives.

Regioselective synthesis of 1-aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated pyrazoles.

[reaction: see text] Highly efficient and regioselective synthesis of 1-aryl-3,4-substituted/annulated-5-(methylthio)pyrazoles and 1-aryl-3-(methylthio)-4,5-substituted/annulated pyrazoles has been reported via cyclocondensation of arylhydrazines with either alpha-oxoketene dithioacetals or beta-oxodithioesters.

Highly regioselective synthesis of 1-aryl-3 (or 5)-alkyl/aryl-5 (or 3)-(N-cycloamino)pyrazoles.

[Reaction: see text]. An efficient highly regioselective protocol for the synthesis of isomeric 1,3-diaryl (or 1-aryl-3-alkyl) and 1,5-diaryl (or 1-aryl-5-alkyl)-5 (or 3)-(N-cycloamino)pyrazoles has been reported by cyclocondensation of common alpha-oxoketene N,S-acetal precursors with arylhydrazines by variation of reaction conditions.