Synthesis and Application of Double Perovskite Bi1.97Eu0.03MoO6 as Heterogeneous and Recyclable Nanocatalyst for Quinoline Synthesis

An efficient and economical protocol for the synthesis of substituted quinolines from various 2-amino aryl ketones and aliphatic ketones in presence of a catalytic quantity of double perovskite Bi1.97Eu0.03MoO6 catalyst, water at ambient temperature to generate the respective quinolines in good yields. The accompanied catalyst had high activity and stability and it might be utilized at least a few times without losing its effectiveness.

DABCO-promoted photocatalytic C–H functionalization of aldehydes

Herein we present a direct application of DABCO, an inexpensive and broadly accessible organic base, as a hydrogen atom transfer (HAT) abstractor in a photocatalytic strategy for aldehyde C–H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the HAT step energetics and determined an optimized geometry for the transition state, showing that the hydrogen atom transfer between aldehydes and DABCO is a mildly endergonic, yet sufficiently fast step. The same calculations were performed with quinuclidine, for comparison of both catalysts and the differences are discussed.

Bile-Acid-Appended Triazolyl Aryl Ketones: Design, Synthesis, In Vitro Anticancer Activity and Pharmacokinetics in Rats

A library of bile-acid-appended triazolyl aryl ketones was synthesized and characterized by detailed spectroscopic techniques such as 1H and 13C NMR, HRMS and HPLC. All the synthesized conjugates were evaluated for their cytotoxicity at 10 µM against MCF-7 (human breast adenocarcinoma) and 4T1 (mouse mammary carcinoma) cells. In vitro cytotoxicity studies on the synthesized conjugates against MCF-7 and 4T1 cells indicated one of the conjugate 6cf to be most active against both cancer cell lines, with IC50 values of 5.71 µM and 8.71 µM, respectively, as compared to the reference drug docetaxel, possessing IC50 values of 9.46 µM and 13.85 µM, respectively. Interestingly, another compound 6af (IC50 = 2.61 µM) was found to possess pronounced anticancer activity as compared to the reference drug docetaxel (IC50 = 9.46 µM) against MCF-7. In addition, the potent compounds (6cf and 6af) were found to be non-toxic to normal human embryonic kidney cell line (HEK 293), as evident from their cell viability of greater than 86%. Compound 6cf induces higher apoptosis in comparison to 6af (46.09% vs. 33.89%) in MCF-7 cells, while similar apoptotic potential was observed for 6cf and 6af in 4T1 cells. The pharmacokinetics of 6cf in Wistar rats showed an MRT of 8.47 h with a half-life of 5.63 h. Clearly, these results suggest 6cf to be a potential candidate for the development of anticancer agents.

Asymmetric benzylic C(sp3)−H acylation via dual nickel and photoredox catalysis

Asymmetric C(sp3)−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C−H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C−H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.