A metal-free cross-dehydrogenative coupling method for the synthesis of N-substituted azoles has been developed. The TBAI/TBHP system catalyzed the coupling of azoles with ethers and thioethers via α-C(sp(3))-H activation. Under the optimized conditions, a diverse range of un/substituted azoles such as 1H-benzimidazole, 9H-purine, 1H-benzotriazole, 1H-1,2,3-triazole, 1H-1,2,4-triazole, and 1H-pyrazole were successfully employed for coupling with various ethers and thioethers such as tetrahydrofuran, tetrahydropyran, 1,4-dioxane, diethyl ether, tetrahydrothiophene, and 1,3-dithiolane.

In the present study, a novel series of 3-pyrimidinylazaindoles were designed and synthesized using a bioinformatics strategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription. The present approach gives new dimensions to the existing SAR and opens a new opportunity for the lead optimizations from comparatively inexpensive starting materials. The study led to the identification of the alternative lead candidate 4ab with a nanomolar potency against CDK2 and CDK9 and potent antiproliferative activities against a panel of tested tumor cell lines along with a better safety ratio of ∼33 in comparison to reported leads. In addition, the identified lead 4ab demonstrated a good solubility and an acceptable in vivo PK profile. The identified lead 4ab showed an in vivo efficacy in mouse triple-negative breast cancer (TNBC) syngeneic models with a TGI (tumor growth inhibition) of 90% without any mortality growth inhibition in comparison to reported leads.

We present a metal-free method for the synthesis of imides by the direct coupling of NH-amides with methylarenes under iodine/aqueous TBHP conditions. The optimized conditions worked very well with benzaldehydes and benzyl alcohol and furnished the corresponding imides in good to excellent yields. A series of control and radical scavenger experiments were also performed, which suggested the involvement of radical pathways. The labeling experiment in the presence of (18)O-labeled H2O suggested water as a source of oxygen in the imides.

We report a new and efficient iron oxide catalyzed cross-coupling reaction between organometallic species such as alkyl/arylmagnesium halides or organolithium species and α-hydrogen bearing cyclic aliphatic ethers via activation of C(sp(3))-H. This is the first example of iron oxide mediated direct C-C bond formation without expensive or toxic ligands.

A metal-free one step coupling reaction between various N-azole rings and diverse α-C(sp)-H containing amides has been developed under oxidative reaction conditions. Commercially available tetrabutyl ammonium iodide (TBAI) in the presence of terbutylhydroperoxide (TBHP), under neat reaction condition, efficiently catalyzed the coupling. Various azole types, such as 1H-benzotriazoles, 1H-1,2,3-triazoles, 1H-1,2,4-triazoles, 1H-tetrazoles, 1H-pyrazoles, and 1H-benzimidazoles, and α-C(sp)-H containing amides, such as N,N-dimethylacetamide, N,N-dimethylbenzamide, N-methylacetamide, N,N-diethylacetamide, N-methylpyrrolidine, and pyrrolidine-2-one, were successfully employed for the coupling. A series of designed and controlled experiments were also performed in order to study the involvement of the different intermediates. Based on the evidence, a plausible mechanism is also proposed. These novel, simple, rapid, attractive, and straightforward transformations open the way of the construction of novel highly functionalized N-azoles via direct covalent N-H bond transformations onto N-C bonds. This approach allows to the synthesis of complex molecules requiring number of steps using classical synthetic ways. In addition, the range of α-C(sp)-H containing amide substrates is virtually unlimited highlighting the potential value of this simple system for the construction of complex heterocyclic molecules, such as fused azoles derivatives.

Here, we report a metal-free cross-coupling reaction of diazines and related heteroarenes with organoboron species via C-H functionalization. The optimized conditions represent a metal-free method for the activation of aryl/heteroarylboronic acids, which undergo coupling with diazines and related heteroarenes. Optimized conditions also find application in the synthesis of a pyrimidine-based potent CDK inhibitor, meriolin1.

We report a new and efficient iron oxide catalyzed cross-coupling reaction between organometallic species such as alkyl/arylmagnesium halides or organolithium species and α-hydrogen bearing cyclic unbranched and branched aliphatic ethers via activation of C(sp(3))-H. In the presence of 1 mol% of iron oxide, five and six membered unbranched cyclic ethers such as tetrahydrofuran and tetrahydropyran gave good to excellent yields of cross-coupled products. Whereas, in case of branched ether such as 2-methyltetrahydrofuran, it was observed that the arylation occurred at both the sides and gave moderate yields of a mixture of regioisomers. Among the organometallic species used, alkyl organometallic reagents gave less yields as compared to aryl organometallics.

Synthesis of 3-sulfenyl indole derivatives is achieved through oxidative cross-dehydrogenative coupling reaction. A few such newly synthesized compounds have also exhibited anti-proliferative activity via reactive oxygen species mediated cell damage.