Rhodium-Catalyzed Annulation of N-Acetoxyacetanilide with Substituted Alkynes: Conversion of Nitroarenes to Substituted Indoles.

A general and efficient rhodium-catalyzed redox-neutral annulation of N-acetoxyacetanilides, readily accessible from nitroarenes, with alkynes has been accomplished for the synthesis of substituted indole derivatives. A wide range of substituted 2,3-diarylindoles were achieved from various substituted N-acetoxyacetanilides and symmetrical/unsymmetrical alkynes in good to excellent yields. The developed method was successfully integrated with the synthesis of N-acetoxyacetanilides for the efficient one-pot synthesis of indoles from nitroarenes. The important features are the introduction of N-acetoxyacetamide as a new directing group, redox-neutral annulation, an additive-free approach, wide functional group tolerance, an intramolecular version, and a one-pot reaction of nitroarenes. The method was further extended to the synthesis of potent higher analogues of indole, viz., pyrrolo[3,2-f]indoles and dibenzo[a,c]carbazoles. In addition, a plausible mechanism was proposed based on the isolation and stoichiometric study of a potential aryl-Rh intermediate.

Cp*Co(III)-catalyzed C2-thiolation and C2,C3-dithiolation of substituted indoles with N-(arylthio)succinimide.

A general and efficient Cp*CoIII-catalyzed C2-thiolation and C2,C3-dithiolation of indole derivatives has been achieved employing N-(aryl/alkylthio)succinimide as a thiolating reagent. This external oxidant-free method utilizes only catalytic amounts of additive and tolerates various functional groups to afford various thiolated products in good yields. Control experiments revealed the importance of the Cp*CoIII-catalyst for both C2- and C3-thiolation.

Metal-Free Directed Diastereoselective C2,C3-Cyclopropanation of Substituted Indoles with Diazoesters.

A metal-free directed C2,C3-cyclopropanation of suitably substituted indoles with α-diazo esters has been accomplished for the diastereoselective synthesis of cyclopropane-fused indolines in good yield. This method works well with a wide range of differently substituted α-diazo esters as well as indole derivatives and shown excellent compatibility for diverse directing group like pyridyl, pyrimidyl, acyl, and urea derivatives. Furthermore, the preliminary mechanistic investigation revealed the importance of directing group for the developed transformation.

Cp*Co(iii)-catalysed selective alkylation of C-H bonds of arenes and heteroarenes with α-diazocarbonyl compounds.

Cp*Co(iii)-catalysed selective alkylation of directed C-H bonds of arenes and heteroarenes has been accomplished employing donor-acceptor carbenes, derived from α-diazocarbonyl compounds. The developed method allows ready access to various substituted α-(hetero)aryl-α-arylacetic acid derivatives in good to excellent yields. Synthetic utility was also shown through the synthesis of a substituted indole derivative, an anticancer agent.

Divergent Functionalization of N-Alkyl-2-alkenylanilines: Efficient Synthesis of Substituted Indoles and Quinolines.

An efficient divergent functionalization of N-alkylated ortho-alkenylanilines to substituted indoles and quinolines has been accomplished by employing rhodium-catalyzed cross-dehydrogenative coupling and silver-mediated oxidative cyclization, respectively. The developed methods tolerate various functional groups and allow the synthesis of substituted indoles and quinolines in good to excellent yield. Synthetic utility is demonstrated through conversion to an indole with antimicrobial activity and C-H bond functionalization of 2-arylquinolines. Furthermore, a plausible mechanism was proposed based on preliminary mechanistic investigations.

Ligand-based Modeling for the Prediction of Pharmacophore Features for Multi-targeted Inhibition of the Arachidonic Acid Cascade.

The single-target drugs against the arachidonic acid inflammatory pathway are associated with serious side effects, hence, as a first step towards multi-target drugs, we have studied the pharmacophoric features common to the inhibitors of 5-lipoxygenase-activating protein (FLAP), microsomal prostaglandin E-synthase 1 (mPGES-1) and leukotriene A4 hydrolase (LTA4H). FLAP and mPGES-1 shared subfamily-specific positions (SSPs) and four mPGES-1 inhibitors binding to them mapped onto the pharmacophore derived from FLAP inhibitors (Ph-FLAP). The reactions of mPGES-1 and LTA4H had high structural similarity. The pharmacophore derived from two substrate mimic inhibitors of LTA4H (Ph-LTA4H) also mapped onto three mPGES-1 inhibitors. Screening of in-house database for Ph-FLAP and Ph-LTA4H identified one compound, C1. It inhibited the production of the mPGES-1 product, prostaglandin E2 (PGE2) by 97.8±1.6 % at 50 µM in HeLa cells and can be a starting point for designing molecules inhibiting all three targets simultaneously.

Cobalt(III)-Catalyzed Intramolecular Cross-Dehydrogenative C-H/X-H Coupling: Efficient Synthesis of Indoles and Benzofurans.

An efficient cobalt(III)-catalyzed intramolecular cross-dehydrogenative C-H/N-H coupling of ortho-alkenylanilines has been developed utilizing O2 as a terminal oxidant. The developed reaction tolerates various reactive functional groups and allows the synthesis of diverse indole derivatives in good to excellent yields. The method was successfully extended to the synthesis of benzofurans through the intramolecular cross-dehydrogenative C-H/O-H coupling of ortho-alkenylphenols.

Rhodium catalyzed arylation of diazo compounds with aryl boronic acids.

A general and efficient synthesis of diarylacetate, a diarylmethine derivative, was accomplished through rhodium catalyzed direct arylation of diazo compounds with arylboronic acids. The reaction tolerates various boronic acid derivatives and functional groups. Notably, chemoselective arylation of diazo compounds over other electrophiles were demonstrated. The efficacy of the developed methodology is shown by the expeditious synthesis of the core structure of diclofensine.