Muhammad Bilal

Nickel-catalyzed reductive hydroxymethylation of aryl electrophiles with α-silicon N -methoxyphthalimides via a radical Brook rearrangement enables late-stage, functional-group-tolerant installation of hydroxymethyl groups.

α-Trifluoromethyl amines are privileged scaffolds in pharmaceuticals and bioactive compounds, serving as metabolically stable amide bioisosteres. However, conventional synthetic approaches often suffer from multistep reactions, limited functional group tolerance, and instability of imine precursors. To overcome these limitations, we report a nickel-catalyzed cross-electrophilic coupling constructing diverse α-trifluoromethylamines via a mechanistically distinct pathway involving solvent-enabled 1,2-hydrogen atom transfer (HAT). In this process, the N–O bond is activated by Ni⁽⁰⁾-promoted SET to form transient N-centered radicals, which undergo DMSO-promoted 1,2-HAT to generate nucleophilic C­(sp³)-centered radicals. These radicals then participate in nickel-catalyzed coupling with a wide range of commercially available aryl halides and vinyl bromides. This strategy suppresses competing C–N bond formation and offers several advantages: the use of bench-stable radical precursors, high chemoselectivity, broad substrate scope, mild reaction conditions, and applicability to the late-stage functionalization of natural products and drug derivatives. Furthermore, the method relies exclusively on earth-abundant nickel and commercially available feedstocks. By leveraging polar solvent-assisted HAT to circumvent traditional intermediates, this methodology enables efficient and scalable synthesis of high-value α-aryl- or alkenyl-substituted α-trifluoromethyl amines.

Transition-metal-catalyzed C-N bond activation has emerged as a powerful yet underdeveloped strategy in synthetic chemistry, largely constrained by the high bond dissociation energy and intrinsic stability of amines. Here, we report a Ni-catalyzed deaminative reductive allylic alkylation and arylation that enables the efficient construction of C-C bonds from readily available arylallylic amines and a broad range of alkyl and aryl halides, providing a robust and stable platform for C-N bond cleavage. This transformation proceeds under mild reductive conditions and displays broad functional group tolerance. Additionally, the reaction is readily scalable to the gram level, and the synthesized products can be subjected to a range of downstream derivatizations.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), in particular hypervirulent and classical strains, represents a severe global health burden with limited treatment options. The urgent need for new antimicrobials motivates the exploration of novel chemical scaffolds. This study focused on substituted thiophene-based thienyl sulfonamides, synthesized via the Suzuki–Miyaura cross-coupling with moderate to excellent yields of unprotected compounds. Evaluation against clinical CRKP isolates revealed significant antibacterial activity for several synthesized sulfonamides. Molecular docking and ADMET profiling further identified compounds 3c, 3f, and 3g as possessing potent activity, promising binding characteristics, and suitable pharmacological properties. These results highlight these thienyl sulfonamides as viable lead candidates for combating multidrug-resistant K. pneumoniae infections.

Electro/photochemical CO₂ conversion yields fuels and chemicals using molecular, SAA/DAC, and MOF-derived catalysts. High activity, selectivity, and stability plus mechanistic insight drive efficient next-gen designs.

Nitriles are valuable compounds because they have widespread applications in organic chemistry. This report details the nickel-catalyzed reductive cyanation of aryl halides and epoxides with cyanogen bromide for the synthesis of nitriles. This robust protocol underscores the practicality of using a commercially available and cost-effective cyanation reagent. A variety of aryl halides and epoxides featuring diverse functional groups, such as -TMS, -Bpin, -OH, -NH₂, -CN, and -CHO, were successfully converted into nitriles in moderate-to-good yields. Moreover, the syntheses at gram-scale and application in late-stage cyanation of natural products and drugs reinforces its potentiality.

In this study, we present a ligand-free nickel^(II)-catalyzed halogen exchange of aromatic halides with magnesium chloride. This method effectively facilitates the retro-Finkelstein reaction for a wide range of aryl bromides, iodides and triflates, demonstrating excellent functional group tolerance. Mechanistic studies reveal that magnesium plays a crucial role in the challenging reductive elimination from Ni^(II) intermediates.

The emergence of extensively drug-resistant Salmonella Typhi (XDR-S. Typhi) poses a grave public health threat due to its resistance to fluoroquinolones and third-generation cephalosporins. This resistance significantly complicates treatment options, underscoring the urgent need for new therapeutic strategies. In this study, we synthesized pyrazine carboxamides (3, 5a–5d) in good yields through the Suzuki reaction. Afterward, we evaluate their antibacterial activities against XDR-S. Typhi via the agar well diffusion method; 5d has the strongest antibacterial activity with MIC 6.25 (mg/mL). Moreover, in vitro Alkaline Phosphatase inhibitor activity was also determined; 5d is the most potent compound, with an IC₅₀ of 1.469 ± 0.02 µM. Further, in silico studies were performed to find the type of interactions between synthesized compounds and target proteins.

Introduction: New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species. Methods: In this study, we successfully synthesized 5-bromo-N-alkylthiophene-2-sulfonamides ( 3a-c) by reacting 5-bromothiophene-2-sulfonamide ( 1) with various alkyl bromides ( 2) using LiH. We also synthesized a series of compounds ( 4a-g) from compound ( 3b) using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56– 72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. Subsequently, we conducted in-silico tests on compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I. Results: The compound ( 3b) with favourable drug candidate status, MIC of 0.39 μg/mL, and MBC of 0.78 μg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions. Conclusion: The 5-bromo-N-alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option.