Hybrid Heterocycles: Ag(I)-Catalyzed C-C/C-N/C-O Coupled Cascade Dual Cyclization to Valuable Indolo-4H-indolones and Indolo-4H-chromenes.

Herein, we report a highly efficient Ag(I)-catalyzed indolyzation with Friedel-Crafts alkylation through a cascade cyclization strategy for accessing valuable hybrid heterocycles for the first time. This general strategy consists of forming four C-C/C-N/C-O bonds toward dual annulation reactions of 2-alkynylanilines with methyl benzoate-2-carboxaldehydes and aromatic amines, as well as with salicylaldehydes and malononitrile. Variably substituted new indolo-4H-phthalimidines and indolo-4H-chromenes were synthesized with excellent yields (85-93%) under mild reaction conditions.

Benzimidates as gem-Diamidation and Amidoindolyzation Cascade Synthons with a Hydrated NiII Catalyst.

We contributed a new benzimidate chemistry through moisture-insensitive NiII/NiII-FeIII combo-catalysis for a simultaneous 2-3 bond-forming gem-diamidation and amidoindolyzation cascade reaction to construct symmetrical and unsymmetrical gem-(arylmethylene)amides and indolo(arylmethylene)amides, using emerging benzimidate synthons. The operational simplicity, mild nature, generality, and robustness of the strategy were validated through syntheses of a wide range of new molecules, labile sugar-based chiral compounds, and pharmaceuticals with high yields under the same reaction conditions.

Nanofibrils of a CuII-Thiophenyltriazine-Based Porous Polymer: A Diverse Heterogeneous Nanocatalyst.

Herein, we report knitting of a thiophenyltriazine-based porous organic polymer (TTPOP) with high surface area and high abundance of nitrogen and sulfur sites, synthesized through a simple one-step Friedel-Crafts reaction of 2,4,6-tri(thiophen-2-yl)-1,3,5-triazine and formaldehyde dimethyl acetal in the presence of anhydrous FeCl3, and thereafter grafting of Cu(OAc)2·H2O in the porous polymer framework to achieve the potential catalyst (CuII-TTPOP). TTPOP and CuII-TTPOP were characterized thoroughly utilizing solid-state 13C-CP MAS NMR, Fourier transform infrared, wide-angle powder X-ray diffraction, thermogravimetric analysis, and X-ray photoelectron spectroscopy and surface imaging by transmission electron microscopy and field emission scanning electron microscopy. The porosity of the nanomaterials was observed in the surface imaging and verified through conducting N2 gas adsorption techniques. Keeping in mind the tremendous importance of C-C and C-N coupling and cyclization processes, the newly synthesized CuII-TTPOP was employed successfully for a wide range of organic catalytic transformations under mild conditions to afford directly valuable diindolylmethanes and spiro-analogues, phthalimidines, propargyl amines, and their sugar-based chiral compounds with high yields using readily available substrates. The highly stable new heterogeneous catalyst showed outstanding sustainability, robustness, simple separation, and recyclability.

A competitive and highly selective 7-, 6- and 5-annulation with 1,3-migration through C-H and N-H - alkyne coupling.

We demonstrated a highly competitive and selective C-C and N-C cross-coupled 7-, 6- and 5-annulation utilizing 2-ethynylanilides to afford functionalized 1H-benzo[b]azepin-2(5H)-ones, 2-quinolinones, and 3-acylindoles in high yield. ZnCl2 was found to be the smart catalyst for 7- and 5-annulation with 1,3-migration through C-H and N-H functionalization, respectively, whereas molecular iodine performed the C-H functionalized 6-annulation with a nonconventional 1,3 H-shift. The mechanism was investigated by intermediate trapping, control, and labeling experiments.

5-Annulation of Ketoimines: TFA-Catalyzed Construction of Isoindolinone-3-carboxylates and Development of Photophysical Properties.

Herein we have demonstrated the first report on 5-annulation of ketoimines to valuable isoindolinone-3-carboxylates. Instead of commonly used aldimine substrates, relatively less reactive ketoimines are employed for developing a TFA catalyzed organoreductive cyclization to furnish a variety of isoindolinones in excellent yield and reaction rate under mild reaction conditions. This is a metal-free event, which proceeds through a one pot ketoimine formation, hydride transfer from an organic reductant 2-(naphthalen-2-yl)-2,3-dihydrobenzo[ d]thiazole, and followed by five member cyclization sequences through TFA-activation of imine and ester groups. Studies on ESI-MS kinetics, leaving group aptitude, and control experiments led us to propose the mechanistic pathway of the new ketoimine-lactamization reaction. We have shown the synthetic utility of the emerging synthons through easy transformation of isoindolinones to different synthetic analogues. We investigated photophysical properties of the small molecules for their futuristic application as a pharmaceutical and materials, and the heterocycles displayed brilliant fluorescence activity.

1,5-Disubstituted 1,2,3-triazole linked disaccharides: Metal-free syntheses and screening of a new class of ribonuclease A inhibitors.

1,5-Regioisomeric triazole linked disaccharides have been synthesized and screened for their inhibitory properties against ribonuclease A (RNase A). The angular constraint-driven 'crescent shaped' inhibitors accommodated themselves into the enzyme active site. An improved enzyme inhibition was observed with increased H-bonding ability of polar functional groups in the modified disaccharides. In this series, introduction of two carboxyl groups in the furanose rings elicited the best result with an inhibition constant of 50 ±â€¯3 µM. This is the first ever report on the use of disaccharides as RNase A inhibitors.

A one-pot synthesis of 2,2'-disubstituted diindolylmethanes (DIMs) via a sequential Sonogashira coupling and cycloisomerization/C3-functionalization of 2-iodoanilines.

A Pd(ii)-Ag(i) catalyzed highly efficient synthesis of diindolylmethane has been developed. This transformation consists of a one-pot sequential Sonogashira coupling (and desilylation) followed by cycloisomerization/C3-functionalization of 2-iodoanilines. Six new bonds (four C-C and two C-N) are formed in a one-pot fashion. A variety of diindolylmethanes were obtained in excellent yields (up to 94%) under mild reaction conditions and this strategy is amenable to gram scale synthesis also. The products were transformed into various synthetically useful compounds.

Highly fluorescent 1,2-dihydropyrimido[1,6-α]indole: an efficient metal free synthesis and photophysical study.

A metal free route to highly fluorescent 1,2-dihydropyrimido[1,6-α]indole derivatives has been developed via base catalyzed aldol followed by the Mannich reaction of indole-2-carboxaldehyde with ethyl N-arylideneglycinate at room temperature. This transformation consists of the sequential formation of two new bonds to afford highly functionalized pyrimidoindole derivatives under mild reaction conditions. Photophysical properties of the products have also been reported.

Unified Approach to Isoindolinones and THIQs via Lewis Acid Catalyzed Domino Mukaiyama-Mannich Lactamization/Alkylations: Application in the Synthesis of (±)-Homolaudanosine.

A novel and efficient synthesis of a variety of isoindolinones and tetrahydroisoquinolines via a Lewis acid catalyzed domino Mukaiyama-Mannich lactamization/alkylation is achieved. This transformation comprises a sequential formation of three new bonds through a one-pot, three-component procedure to afford product in moderate to high yields. A concise synthesis of (±)-homolaudanosine (2b) has been achieved using this method.

1,5-disubstituted 1,2,3-triazolylation at C1, C2, C3, C4, and C6 of pyranosides: a metal-free route to triazolylated monosaccharides and triazole-linked disaccharides.

A pair of easily accessible vinyl sulfones derived from styrene epoxide and monotosylated glycerol were reacted with six different azidopyranosides having an azido group at C1, C2, C3, C4, C6, and at the terminal position of an exocylic chain attached to C1. The reaction was performed mostly in water at elevated temperature without any metal catalyst to afford regioselectively 1,5-disubstituted triazolylated pyranosides in high yields. Another set of exocyclic vinyl sulfones prepared from 3-O-methylated- and 3-O-benzylated glucofuranosides as well as 3-O-benzylated allofuranoside were also subjected to 1,3-dipolar cycloaddition reactions with six azidopyranosides under similar reaction conditions to generate a series of 1,5-disubstituted triazole-linked disaccharides. The synthesis of all 1,5-disubstituted triazolylated monosaccharides as well as all 1,5-disubstituted triazole linked disaccharides are reported for the first time. Steric bulk around the azido and vinyl sulfone groups plays a significant role in deciding the outcome of the reactions. This powerful and practical route has the potential to be exploited for the synthesis of complex 1,5-disubstituted 1,2,3-triazolylated carbohydrates.