G Sekar

Zn(OTf) 2 -catalyzed synthesis of 3,3′-bisindolyl acetamides from α-keto amides is developed. Both aromatic α-keto amides substituted with electron-donating as well as -withdrawing groups and aliphatic α-keto amides are well tolerated to provide symmetrical bisindoles in moderate to excellent yields. The chemoselective bisindolylation of the keto group of α-keto amides in the presence of a simple keto functionality is successfully achieved in good yields. The transformation is further extended to the synthesis of challenging unsymmetrical bisindoles by treating indolyl α-hydroxy amides with substituted indoles. The unsymmetrical bisindoles are isolated in good to excellent yields.

An efficient protocol for the synthesis of thioether directly from heteroarenes has been developed in the presence of visible light in a one-pot manner at room temperature. This method involves two sequential reactions in a single pot where the formation of the iodinated heteroarene is followed by a transition-metal-free C-S coupling reaction. A wide range of heteroarene and thiol partners (including aliphatic thiols) have been used for the synthesis of thioethers. NMR studies and DFT calculations revealed the presence of a halogen bond between the thiolate anion (halogen bond acceptor) and iodoheteroarene (halogen bond donor). This halogen bonded complex on photoexcitation facilitates the electron transfer from the thiolate anion to the iodoheteroarene at room temperature.

Synthesis of enantiomerically enriched α-hydroxy amides and β-amino alcohols has been accomplished by enantioselective reduction of α-keto amides with hydrosilanes. A series of α-keto amides were reduced in the presence of chiral CuII/(S)-DTBM-SEGPHOS catalyst to give the corresponding optically active α-hydroxy amides with excellent enantioselectivities by using (EtO)3SiH as a reducing agent. Furthermore, a one-pot complete reduction of both ketone and amide groups of α-keto amides has been achieved using the same chiral copper catalyst followed by tetra-n-butylammonium fluoride (TBAF) catalyst in presence of (EtO)3SiH to afford the corresponding chiral β-amino alcohol derivatives.

A wide range of 2-aryl or 2-alkyl-substituted benzothiazoles are synthesized through intramolecular C(aryl)-S bond forming-cyclization using copper(II)-BINAM-catalyzed coupling of less reactive N-(2-chlorophenyl) benzo or alkylthioamide under mild reaction conditions (82 °C). © 2010 Elsevier Ltd. All rights reserved.

Metal-free halogen(I) catalysts were used for the selective oxidation of aryl(heteroaryl)methanes [C(sp3)−H] to ketones [C(sp2)=O] or esters [C(sp3)−O]. The synthesis of ketones was performed with a catalytic amount of NBS in DMSO solvent. Experimental studies and density functional theory (DFT) calculations supported the formation of halogen bonding (XB) between the heteroarene and N-bromosuccinimide, which enabled imine–enamine tautomerism of the substrates. No additional activator was required for this crucial step. Isotope-labeling and other supporting experiments suggested that a Kornblum-type oxidation with DMSO and aerobic oxygenation with molecular oxygen took place simultaneously. A background XB-assisted electron transfer between the heteroarenes and halogen(I) catalysts was responsible for the formation of heterobenzylic radicals and, thus, the aerobic oxygenation. For selective acyloxylation (ester formation), a catalytic amount of iodine was employed with tert-butyl hydroperoxide in aliphatic carboxylic acid solvent. Several control reactions, spectroscopic studies, and Time-Dependent Density Functional Theory (TD–DFT) calculations established the presence of acetyl hypoiodite as an active halogen(I) species in the acetoxylation process. With the help of a selectivity study, for the first time we report that the strength of the XB interaction and the frontier orbital mixing between the substrates and acyl hypoiodites determined the extent of the background electron-transfer process and, thus, the selectivity of the reaction.

A wide range of 2-arylbenzo[b]furans are synthesized through domino intermolecular C(aryl)-C(alkynyl) bond formation followed by intramolecular C(alkynyl)-O bond forming cyclization via copper(II)-catalyzed coupling of o-iodophenols and aryl terminal acetylenes. This method requires neither expensive palladium catalyst nor oxophilic phosphine ligands, can tolerate different functional groups. The methodology is successfully utilized in formal synthesis of β-amyloid aggregation inhibitor 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4-methoxyphenyl) benzofuran. © 2010 Elsevier Ltd. All rights reserved.

An efficient diastereoselective synthesis of α- tetralone-fused spirooxindoles is reported. The Pd-catalyzed domino reaction proceeds through a carbene migratory insertion followed by a 6-endo-trig mode of conjugate addition sequence from easily accessible isatin-derived N-tosylhydrazones and 2'-iodochalcones. The versatility of the protocol has been showcased by high functional group tolerance, broad substrate scope, and extension to an expedient synthesis of spiroacenaphthylenes. NMR reaction profiling and deuterium-labeling investigations provide insight into the mechanistic pathway.

A DABCO-copper(I) chloride complex (5 mol%) together with TEMPO (5 mol%) in nitromethane as solvent has been used as an efficient catalytic system for the selective oxidation of benzylic and allylic alcohols into the corresponding carbonyl compounds at room temperature where molecular oxygen acts as an ultimate, stoichiometric oxidant and water is the only by-product. The solidstate structure determination of the DABCOcopper complex shows that the copper is in the + II oxidation state with trigonal bipyramidal geometry and exists in a linear polymeric structure due to strong hydrogen bonding. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.

A novel method to synthesize isoquinolones via oxidative annulation of N-alkoxy benzamides and alkynes using binaphthyl-stabilized palladium nanoparticles (Pd-BNP) as catalyst has been developed. This methodology affords various isoquinolone derivatives in good to excellent yields with high regioselectivities in the presence of air as oxidant. N-Methoxybenzothioamide was also found to undergo oxidative annulation with alkyne successfully and provided a sulfur analogue of isoquinolones in moderate yields. The Pd-BNP catalyst was easily recovered and reused up to four times without any apparent agglomeration. (Figure presented.).

D-Glucosamine is introduced for the first time as a green ligand with copper in a coupling reaction to synthesize anilines. The reaction proceeds in a domino fashion by the in situ reduction of aryl azides formed from aryl halides and NaN3. The high water solubility of the ligand enables easy catalyst removal. © 2011 The Royal Society of Chemistry.