Letters in Organic Chemistry - Volume 19, Issue 8, 2022

Chiral allenylcarbonyls such as allenoates remain underutilized in complex synthesis despite recent advances in synthesis methods to prepare them non-racemically. The field is now ripe for the employment of this class of allenes as building blocks to facilitate the construction of complex small-molecule compounds, such as bridged bicycles.

The synthesis of advanced substituted 3-pentafluorosulfanylphenol/anisole was accomplished starting from the easy to access and commercially available 3-pentafluorosulfanylphenol. These products bear diverse substitutions such as ester, aldehyde, halogens, alcohol, nitrile and carboxylic acid and could be in the future used as high-value building blocks for the synthesis of various scaffolds. For our part, this intermediate had been used to synthesize a library of 2-arylindadiones substituted by a pentafluorosulfanyl group.

The aza-Michael addition is an attractive methodology for synthetic organic chemistry because the resulting β-aminocarbonyl compounds are valuable building blocks for the synthesis of pharmaceutically useful compounds. However, monoalkylation of aniline and its derivatives is quite difficult because anilines are poor nucleophiles compared to monoalkylated ones. Since the publication of pioneering articles in 1986, the development of microwave-assisted organic synthesis has been remarkable. Therefore, we began by investigating the monoalkylation of aniline and its derivatives under microwave irradiation. Because of the ready formation of bisalkylated products, the monoalkylation reaction between anilines and Michael acceptors is quite difficult. To overcome the difficulty, we investigated the effect of microwave irradiation for the alkylation of anilines with chalcones as Michael acceptors. Microwave-assisted aza-Michael addition proceeded smoothly to obtain mainly the monoalkylated Michael adduct. The substitution effects of both chalcone and aniline concerning the yield were also studied. We supposed that dimer formation by two monoalkylated compounds produces a bulky environment around the amino group, which prevents monoalkylated compounds from undergoing a second alkylation. We confirmed a highly efficient and rapid method for preparing monoalkylated anilines using microwave-assisted aza-Michael addition between anilines and chalcones.

A novel magnetite silica-coated nanoparticle-supported molybdate nanocatalyst has been prepared successfully by a simple co-precipitation method. Prepared nanocatalyst has been characterized by different techniques like Fourier Transmission Infrared Spectroscopy (FT-IR), X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FE-SEM), and Energy Dispersive X-ray Spectroscopy (EDX). Further, the catalytic activity of the nanocatalyst was explored for N-formylation reactions under solvent-free conditions. Interestingly, the catalyst could be reused for 10 cycles, and only 2 mol % of the catalyst was sufficient to catalyze the N-formylation reaction at 70°C under solvent-free conditions.

A practical and promising protocol was developed for N-arylations of various aromatic amines. This protocol was carried out through the coupling reaction between various aryl halides and phenylboronic acid using iron (III). The processes are efficiently promoted by the catalyst system involving the environmentally benign iron (III) and the state PPh3. The advantages of this method are its versatility, convenient operation and low cost, along with the yields, which are remarkably improved under ultrasonic irradiation, and the high purity of the products obtained. The catalyst can be magnetic recycled via an external magnet and reused several times without considerable loss of its catalytic activity.

Operculina turpethum (Linn.) Silva Manso belongs to the family convolvulaceae. It is an important plant in the Indian conventional system of medicine, which is extensively employed by different tribes in many countries to cure edema and painful conditions like arthritis, back pain, hyperlipidemia, diabetes mellitus, liver disorders, skin disorders, and regulation of bowel functions. The roots of O. turpethum (Linn.) were subjected to physicochemical and phytochemical standardization and chromatographic separation, which was accomplished by column chromatography, TLC, and HPTLC. Further, the acute toxicity, cytotoxic and anti-inflammatory activities of Operculina turpethum roots were estimated by in vivo and in vitro models. This study includes percentage yield of extraction and organoleptic evaluation, along with the analysis of its physicochemical investigations and preliminary phytochemical estimation. The isolation of active phytoconstituents was done by column chromatography, and the isolated compound was then exposed to TLC and HPTLC analysis. Cytotoxic activity was tested by WST-1 based cell viability assay on HepG2 cells. The anti-inflammatory activity of methanol extract (ME) was evaluated against inflammation occur by both in vitro and in vivo methods. The methanolic extract exhibited the presence of most of the phytoconstituents out of all the extracts. The phytoconstituent phytosterol, i.e., β-sitosterol, was isolated by column chromatography, identified, and quantified by TLC and HPTLC, which was liable for anti-inflammatory activity. The amount of β- sitosterol was estimated to be 14.09 μg in a 10.00 mg fraction of MEOT. MEOT was devoid of toxicity up to 2000 mg/kg in Wistar albino rats. It was analysed that in vitro anti-inflammatory activity of MEOT by egg albumin denaturation method exhibited an incredible decrement in turbidity and increased the percentage inhibition of albumin denaturation (60.52%) in MEOT treated group as compared with the control group. In egg albumin-induced edema in rats, MEOT at the dose of 400 mg/kg reduced the edema formation (3.03 ± 0.02) induced by egg albumin at 4th h. In cotton pellet-induced granuloma in rats, MEOT at the dose of 400 mg/kg displayed maximum granuloma inhibition (51.06%), which was similar to that of indomethacin. From the obtained findings, it is confirmed that O. turpethum contains β-sitosterol, which is responsible for potent anti-inflammatory activity without causing cytotoxicity to the plant. The results suggested that ME of O. turpethum roots had a high potential for application as an anti-inflammatory agent. The recognization and confirmation of the plant can be obtained from the study and will present data that is aidful in determining the quality and purity of a crude drug which further helps in preventing its adulteration.

We reported Chickpea leaf exudates (CLEs) as a Brønsted acid, naturally available biodegradable, eco-friendly, and reusable reaction medium for highly efficient and facile one-pot synthesis of pyran-annulated heterocyclic systems, like 7-aryl-benzopyrano[4,3-b]benzopyran-6,8- diones,tetrahydrobenzo[b]pyran, and dihydropyrano[c]chromenes scaffolds. The analogous products were obtained via tandem Knoevengel-Michael addition and cyclo condensation reaction in ethanol at room temperature with 90-96% yields in a short reaction time. Moreover, the reaction media containing Bronsted acids can be easily recovered and reused up to five times, slightly decreasing product yields.

Halogenated furanones have been found to act as potent quorum sensing inhibitors in several bacterial species. It is believed that dihalofuranones covalently bind to the LuxS enzyme, which is necessary for autoinducer-2 synthesis. In addition to their antimicrobial activity, halogenated furanones also possess anti-cancer, antioxidant, and depigmentation properties. However, traditional routes to these compounds are low-yielding and capricious. The aim of this study was to investigate higher-yielding preparations of gem-dihalofuranones and compare their reactivity using Suzuki chemistry. Ramirez dibromoolefination of maleic anhydride was optimised using a variety of conditions. A similar route was investigated for the preparation of bromofluorofuranones and dichlorofuranones. The conversion of a dichlorofuranone to the corresponding iodofuranone derivatives using microwave-assisted Finkelstein chemistry was also studied. Lastly, the reactivity of the different dihalofuranones was compared by Pd-mediated coupling with phenylboronic acid. A higher- yielding, concise synthesis of dibromofuranones was developed using a modified Ramirez reaction. Additionally, a telescoped preparation of dichlorofuranone was higher yielding than previous approaches. Bromine- and iodine-substituted dihalofuranones proved more reactive than their chlorine- substituted analogues. Higher yielding routes to bromine-, fluorine-, chlorine- and iodinecontaining dihalofuranones were successfully developed. Suzuki couplings of gem-dihalofuranones were found to proceed with high stereoselectivity.

In the present manuscript, we easily synthesized three different types of ionic liquid supported 3-quinuclidinone organocatalysts such as [PyAmEQ][BF4] (Py-CATALYST-1), [PyAmEQ][PF6] (Py-CATALYST-2), and [PyAmEQ][NTf2] (Py-CATALYST-3). After performing the careful characterization of the above catalysts with sophisticated analytical techniques, we utilized them as a catalyst to study the passive Morita-Baylis-Hillman reaction. The corresponding Morita-Baylis-Hillman adducts were easily isolated, followed by the simple ether extraction method. Moreover, the above protocol also promoted low catalyst loading, short reaction time, wide substrate scope, easy product, and catalyst recycling. We easily recycled the catalytic system for 5 runs with no noticeable loss in the chemical yield. Additionally, Py-CATALYST-3 was also used to prepare biologically active materials, i.e., N-((E,3S,4R)-5-benzylidene-tetrahydro-4-hydroxy-6-oxo- 2H-pyran-3-yl) palmitamide derivatives.

The isosteviol derived bifunctional primary amine-squaramide organocatalysts were applied in the Michael addition between nitroalkenes and acetophenone. The conjugate addition isomers of two configurations were observed with high yields (up to 93% yield) and good enantioselectivity (up to 91% ee) at room temperature.