Reactive Compounds Research Articles

Accurate measurement of sulfhydryls and TCEP-releasable sulfhydryls in the liquid phase of wine that contribute to ‘reductive’ aromas using LC-MS/MS

Volatile sulfur compounds (VSCs) are important aroma and flavour characters in food and beverage products. The identification and quantification of these extremely reactive and volatile compounds pose analytical challenges which demand selective and sensitive methods. In this study, a novel quantification method was developed to analyse sulfhydryls as well as the total pool of sulfhydryls which can be released after tris(2-carboxyethyl)phosphine (TCEP) addition from disulfides, polysulfides, metal-bound and other yet to be identified sources naturally present in wine. The majority of methods for VSC quantification analyse VSCs in wine headspace, whereas this method measures sulfhydryls and TCEP-releasable sulfhydryl species, which likely include free and metal-bound sulfhydryl forms, in the liquid phase of wine using UHPLC-MS/MS. Sulfhydryls were derivatised with N-(2-ferroceneethyl) maleimide (FEM), subsequently, followed by differential labelling of sulfhydryls released after TCEP addition with ferrocenecarboxylic acid-(2-maleimidoyl)ethylamide (FMEA). Analysis of commercial wines revealed the presence of hydrogen sulfide, methanethiol, ethanethiol, and 2-mercaptoethanol at aroma-active concentrations. Significant positive correlations were found between MeSH and CH3–S-R TCEP-releasable species, and significant positive correlations were found between EtSH and CH3–CH2–S-R TCEP-releasable species. This method provides important information on sulfhydryls, and may also provide insights into a wine's risk of developing ‘reductive’ faults post-bottling from latent sources.

Reactivity of Superbasic Carbanions Generated via Reductive Radical-Polar Crossover in the Context of Photoredox Catalysis.

Photocatalytic reactions involving a reductive radical-polar crossover (RRPCO) generate intermediates with carbanionic reactivity. Many of these proposed intermediates resemble highly reactive organometallic compounds. However, conditions of their formation are generally not tolerated by their isolated organometallic versions and often a different reactivity is observed. Our investigations on their nature and reactivity under commonly used photocatalytic conditions demonstrate that these intermediates are indeed best described as free, superbasic carbanions capable of deprotonating common polar solvents usually assumed to be inert such as acetonitrile, dimethylformamide, and dimethylsulfoxide. Their basicity not only towards solvents but also towards electrophiles, such as aldehydes, ketones, and esters, is comparable to the reactivity of isolated carbanions in the gas-phase. Previously unsuccessful transformations thought to result from a lack of reactivity are explained by their high reactivity towards the solvent and weakly acidic protons of reaction partners. An intuitive explanation for the mode of action of photocatalytically generated carbanions is provided, which enables methods to verify reaction mechanisms proposed to involve an RRPCO step and to identify the reasons for the limitations of current methods.

Nitrogen compounds at Mexican and USA coasts on the Gulf of Mexico

In recent decades, anthropogenic emissions in the Gulf of Mexico have caused a deterioration in air quality in surrounding areas, mainly due to particulate matter, sulfur dioxide and nitrogen dioxide. Over this period, interest in reactive nitrogen compounds has increased due to their relationships to air quality and ecosystem impacts associated with atmospheric deposition. In this study we summarize air concentrations of nitrogen dioxide in ambient air and wet atmospheric deposition of nitrate and ammonium along the southern coast of the United States of America and eastern Mexico over the period 2017 to 2020. The highest concentrations of ammonium and nitrate were observed in precipitation at Texas and sites in Mexico, although the highest rates of atmospheric deposition were observed in Florida and Louisiana. The ratio between ammonium and nitrate in precipitation was higher at Mexican stations than in studied sites in the United States, influenced by meteorological factors, atmospheric emissions, and characteristic air mass transport in the region. Back trajectory modeling showed the importance of the seasonality of the wind in the transport of nitrogen compounds of local and regional origin that affect Veracruz.

What are the DNA lesions underlying formaldehyde toxicity?

Formaldehyde is a highly reactive organic compound. Humans can be exposed to exogenous sources of formaldehyde, but formaldehyde is also produced endogenously as a byproduct of cellular metabolism. Because formaldehyde can react with DNA, it is considered a major endogenous source of DNA damage. However, the nature of the lesions underlying formaldehyde toxicity in cells remains vastly unknown. Here, we review the current knowledge of the different types of nucleic acid lesions that are induced by formaldehyde and describe the repair pathways known to counteract formaldehyde toxicity. Taking this knowledge together, we discuss and speculate on the predominant lesions generated by formaldehyde, which underly its natural toxicity.

Effects of Halides on Organic Compound Degradation during Plasma Treatment of Brines.

Plasma has been proposed as an alternative strategy to treat organic contaminants in brines. Chemical degradation in these systems is expected to be partially driven by halogen oxidants, which have been detected in halide-containing solutions exposed to plasma. In this study, we characterized specific mechanisms involving the formation and reactions of halogen oxidants during plasma treatment. We first demonstrated that addition of halides accelerated the degradation of a probe compound known to react quickly with halogen oxidants (i.e., para-hydroxybenzoate) but did not affect the degradation of a less reactive probe compound (i.e., benzoate). This effect was attributed to the degradation of para-hydroxybenzoate by hypohalous acids, which were produced via a mechanism involving halogen radicals as intermediates. We applied this mechanistic insight to investigate the impact of constituents in brines on reactions driven by halogen oxidants during plasma treatment. Bromide, which is expected to occur alongside chloride in brines, was required to enable halogen oxidant formation, consistent with the generation of halogen radicals from the oxidation of halides by hydroxyl radical. Other constituents typically present in brines (i.e., carbonates, organic matter) slowed the degradation of organic compounds, consistent with their ability to scavenge species involved during plasma treatment.

Elucidating the anti-cancer potential of Cinnamomum tamala essential oil against non-small cell lung cancer: A multifaceted approach involving GC-MS profiling, network pharmacology, and molecular dynamics simulations

Cinnamomum tamala (Buch.-Ham.) T.Nees & Eberm., or Indian Bay Leaf, is a well-known traditional ayurvedic medicine used to treat various ailments. However, the molecular mechanism of action of Cinnamomum tamala essential oil (CTEO) against non-small cell lung cancer (NSCLC) remains elusive. The present study aims to decipher the molecular targets and mechanism of CTEO in treating NSCLC. GC-MS analysis detected 49 constituents; 44 successfully passed the drug-likeness screening and were identified as active compounds. A total of 3961 CTEO targets and 4588 anti-NSCLC-related targets were acquired. JUN, P53, IL6, MAPK3, HIF1A, and CASP3 were determined as hub genes, while cinnamaldehyde, ethyl cinnamate and acetophenone were identified as core compounds. Enrichment analysis revealed that targets were mainly involved in apoptosis, TNF, IL17, pathways in cancer and MAPK signalling pathways. mRNA expression, pathological stage, survival analysis, immune infiltrate correlation and genetic alteration analysis of the core hub genes were carried out. Kaplan-Meier overall survival (OS) curve revealed that HIF1A and CASP3 are linked to worse overall survival in Lung Adenocarcinoma (LUAD) cancer patients compared to normal patients. Ethyl cinnamate and cinnamaldehyde showed high binding energy with the MAPK3 and formed stable interactions with MAPK3 during the molecular dynamic simulations for 100 ns. The MM/PBSA analysis revealed that van der Waals (VdW) contributions predominantly account for a significant portion of the compound interactions within the binding pocket of MAPK3. Density functional theory analysis showed cinnamaldehyde as the most reactive and least stable compound. CTEO exhibited selective cytotoxicity by inhibiting the proliferation of A549 cells while sparing normal HEK293 cells. CTEO triggered apoptosis by arresting the cell cycle, increasing ROS accumulation, causing mitochondrial depolarisation, and elevating caspase-3, caspase-8 and caspase-9 levels in A549 cells. The above study provides insights into the pharmacological mechanisms of action of Cinnamomum tamala essential oil against non-small cell lung cancer treatment, suggesting its potential as an adjuvant therapy.

Efficiency of ozonation and sulfate radical - AOP for removal of pharmaceuticals, corrosion inhibitors, x-ray contrast media and perfluorinated compounds from reverse osmosis concentrates

This study investigated the elimination of pharmaceuticals, corrosion inhibitors, x-ray contrast media and perfluorinated compounds from reverse osmosis concentrates during ozonation and UV/persulfate processes. Second-order rate constants for the reactions of candesartan, irbesartan, methyl-benzotriazole, and chloro‑benzotriazole with sulfate radical (SO4·−) were determined for the first time. Experiments were conducted in buffered pure water, in buffered water added with the matrix substituents chloride, carbonate, NOM, and reverse osmosis concentrate with spiked micropollutants (MP). UV/persulfate eliminated all MP to a higher extent than ozonation in RO concentrates due to the higher yield of oxidative species and photolytic degradation. Compounds with electron-rich moieties such as carbamazepine, diclofenac, metoprolol, and sulfamethoxazole were completely eliminated with small ozone doses (< 0.5 mg O3 / mg DOC) and with a small fluence (< 5000 J m−2) in UV/persulfate processes. Photosensitive compounds with high reactivity towards hydroxyl radicals (·OH) and SO4·− like the x-ray contrast media Iopamidol, Iohexol, and Amidotrizoic acid were successfully eliminated with a reasonable fluence in UV/persulfate, whereas these compounds persist in ozonation at common ozone dosages. However, much higher fluences and ozone dosages were required for the least reactive compounds like the class of benzotriazoles. Comparing the application of both oxidative processes to the RO concentrate, ozonation has the disadvantage of forming bromate. The energy input of both processes strongly depends on the target compounds to be eliminated. For the elimination of compounds such as sulfamethoxazole, ozonation is a feasible technique, whereas UV/persulfate is better suited for the elimination of recalcitrant compounds such as x-ray contrast media. In general, oxidative process treatment of RO concentrate could be applied to partly abate micropollutants before discharge.

Examining the benefits of extended patch test series in children: a comprehensive analysis.

The growing presence of allergens in materials and scarce data on allergic contact dermatitis in children has increased our need to refine its diagnosis in this population. We aimed to analyze children's specific responsivity to highly reactive subcomponents of Fragrance mix I, Fragrance mix II, and Textile dye mix from the European baseline series. We retrospectively analyzed patch test records of children aged 2 to 18 who underwent patch testing with the European baseline series between 2014 and 2022 in Israel. A total of 367 children were included in the study. In all, 160 children had positive results; 43 patients reacted to one of the mixes, and 20 performed further testing. Eleven of them completed the extended series at the exact same times as the regular European series, which benefited children. Farnesol was the most reactive compound (30.8%). Performing the extended European series provides a more accurate and time-efficient allergic contact dermatitis diagnosis. Farnesol reactivity appears prominent in children and may justify tighter product regulations.

Formaldehyde Exposure Racial Disparities in Southeast Texas.

Formaldehyde (HCHO) exposures during a full year were calculated for different race/ethnicity groups living in Southeast Texas using a chemical transport model tagged to track nine emission categories. Petroleum and industrial emissions were the largest anthropogenic sources of HCHO exposure in Southeast Texas, accounting for 44% of the total HCHO population exposure. Approximately 50% of the HCHO exposures associated with petroleum and industrial sources were directly emitted (primary), while the other 50% formed in the atmosphere (secondary) from precursor emissions of reactive compounds such as ethylene and propylene. Biogenic emissions also formed secondary HCHO that accounted for 11% of the total population-weighted exposure across the study domain. Off-road equipment contributed 3.7% to total population-weighted exposure in Houston, while natural gas combustion contributed 5% in Beaumont. Mobile sources accounted for 3.7% of the total HCHO population exposure, with less than 10% secondary contribution. Exposure disparity patterns changed with the location. Hispanic and Latino residents were exposed to HCHO concentrations +1.75% above average in Houston due to petroleum and industrial sources and natural gas sources. Black and African American residents in Beaumont were exposed to HCHO concentrations +7% above average due to petroleum and industrial sources, off-road equipment, and food cooking. Asian residents in Beaumont were exposed to HCHO concentrations that were +2.5% above average due to HCHO associated with petroleum and industrial sources, off-road vehicles, and food cooking. White residents were exposed to below average HCHO concentrations in all domains because their homes were located further from primary HCHO emission sources. Given the unique features of the exposure disparities in each region, tailored solutions should be developed by local stakeholders. Potential options to consider in the development of those solutions include modifying processes to reduce emissions, installing control equipment to capture emissions, or increasing the distance between industrial sources and residential neighborhoods.

When Does Multiphase Chemistry Influence Indoor Chemical Fate?

Human chemical exposure often occurs indoors, where large variability in contaminant concentrations and indoor chemical dynamics make assessments of these exposures challenging. A major source of uncertainty lies in the rates of chemical transformations which, due to high surface-to-volume ratios and rapid air change rates relative to rates of gas-phase reactions indoors, are largely gas-surface multiphase processes. It remains unclear how important such chemistry is in controlling indoor chemical lifetimes and, therefore, human exposure to both parent compounds and transformation products. We present a multimedia steady-state fugacity-based model to assess the importance of multiphase chemistry relative to cleaning and mass transfer losses, examine how the physicochemical properties of compounds and features of the indoor environment affect these processes, and investigate uncertainties pertaining to indoor multiphase chemistry and chemical lifetimes. We find that multiphase reactions can play an important role in chemical fate indoors for reactive compounds with low volatility, i.e., octanol-air equilibrium partitioning ratios (Koa) above 108, with the impact of this chemistry dependent on chemical identity, oxidant type and concentration, and other parameters. This work highlights the need for further research into indoor chemical dynamics and multiphase chemistry to constrain human exposure to chemicals in the built environment.

The Effect of Administration of Rosella Flower (Hibiscus Sabdariffa) Extract Gel on The Expression Of TNF-α And Caspase-3 Expression in An In Vivo Study of Wistar Strain Rats Exposed to Ultraviolet B-Lights

UV rays are oxidative because they can produce Reactive Oxygen Species and free radical compounds. The dangers of sun exposure can cause skin disorders such as aging at an early age (photoaging). Rosella flower petals can be used in medicine, jams, and natural food coloring because they contain flavonoids as antioxidants or free radical scavengers. The research aimed to determine the effect of administering Rosella (Hibiscus sabdariffa L.) flower extract gel on TNF-α expression and Caspase-3 expression in an in vivo study of Wistar mice exposed to UVB. This research is an experimental study. The sample for each treatment group consisted of 6 individuals, so the total research sample was 24. Data analysis used descriptive, normality, and homogeneity tests with data analysis processing using SPSS 25.0 for Windows. The study found that administration of rosella flower extract gel with a concentration of 15% effectively reduced the expression of TNF-α and Caspase-3 in mice exposed to UVB light and produced filled and dense collagen. So, it can be concluded that rosella flower extract gel can act as an antioxidant that inhibits the growth of TNF-α and Caspase-3 expression.

Autonomous execution of highly reactive chemical transformations in the Schlenkputer

We design a modular programmable inert-atmosphere Schlenkputer (Schlenk-line computer) for the synthesis and manipulation of highly reactive compounds, including those that are air and moisture sensitive or pyrophoric. Here, to do this, we constructed a programmable Schlenk line using the Chemputer architecture for the inertization of glassware that can achieve a vacuum line pressure of 1.5 × 10−3 mbar, and integrated a range of automated Schlenk glassware for the handling, storage and isolation of reactive compounds at sub-ppm levels of O2 and H2O. This has enabled automation of a range of common organometallic reaction types for the synthesis of four highly reactive compounds: [Cp2TiIII(MeCN)2]+, CeIII{N(SiMe3)2}3, B(C6F5)3 and {DippNacNacMgI}2, which are variously sensitive to temperature, pressure, water and oxygen. Automated crystallization, filtration and sublimation are demonstrated, along with analysis using inline nuclear magnetic resonance or reaction sampling for ultraviolet–visible spectroscopy. Finally, we demonstrate low-temperature reactivity down to −90 °C as well as safe handling and quenching of alkali metal reagents using dynamic feedback from an in situ temperature probe.

Measurements of atmospheric C10–C15 biogenic volatile organic compounds (BVOCs) with sorbent tubes

Abstract. Biogenic volatile organic compounds (BVOCs; e.g. terpenes) are highly reactive compounds typically present at sub-parts-per-billion mole fractions in the air. Due to this, their measurements are challenging and they may suffer losses during sampling, storage and analyses. Even though online measurements of BVOCs are becoming more common, the use of sorbent tubes is expected to continue because they offer greater spatial coverage compared to online measurements, and no infrastructure (e.g. electricity, housing/shelter with stable temperature and humidity, sampling lines) is required for sampling. In this study, the performance of an offline technique for the measurement of BVOCs based on sorbent tube sampling was evaluated. Tested compounds included eight monoterpenes, five sesquiterpenes and five oxygenated BVOCs, which are generally either directly emitted (1,8-cineol, linalool, bornyl acetate) or oxidation products (nopinone and 4-acetyl-1-methylcyclohexene). Two sorbent materials (Tenax TA and Carbopack B) and four tube materials (stainless steel (SS), SilcoNert 1000, glass and glass-coated SS) were used. The laboratory evaluations determined the storage stability, breakthrough volumes, suitable tube materials, recovery from ozone scrubbers and particulate filters, and sampling efficiency. In addition, an intercomparison between two laboratories was conducted. No multibed configurations were tested. Of the sorbent materials Tenax TA showed acceptable results for these BVOCs, while with Carbopack B losses and increases in some compounds were detected. Studied compounds were found to be stable in Tenax TA tubes for at least 1 month at −20 and at +20 ∘C. Breakthrough tests indicated that α- and β-pinene have clearly lower breakthrough volumes in the Tenax TA tubes used (4–7 and 8–26 L, respectively) than other terpenes (&gt; 160 L). SS, SilcoNert 1000 and glass were all shown to be suitable tube materials. Results from Tenax TA sorbent tube sampling agreed with online sampling for most compounds. Heated SS tubes, sodium thiosulfate filters and KI/Cu traps were found to be suitable ozone scrubbers for the studied BVOCs. Tested particle filters had a greater impact on limonene (relative difference &lt; +7 %) than on α- and β-pinene (relative difference ±2 %). The laboratory intercomparison of α- and β-pinene measurements showed that in general, measured values by the two laboratories were in good agreement with Tenax TA.

Fifty years of environmental progress for United States dairy farms

Dairy farms in the United States have changed in many ways over the past 50 yr. Milk production efficiency has increased greatly, with ∼30% fewer cows producing about twice the amount of milk today. Other improvements include increases in crop yields, fuel efficiency of farm equipment, and efficiency in producing most resources used on farms (e.g. electricity, fuel, fertilizer). These improvements have led to changes in the environmental impact of farms. Through simulation of representative dairy farms in 1971 and 2020, changes in nutrient losses and farmgate life cycle assessments of greenhouse gas (GHG) emissions, fossil energy use, and blue (ground and surface) water use were determined for 6 regions and the United States. For all environmental metrics studied, intensities expressed per unit of fat- and protein-corrected milk produced were reduced, but the total effects over all farms or milk produced increased for 5 of the 13 environmental metrics. Reductions in the impacts of dairy farms in the eastern United States were offset by large increases in western regions because of a major increase in cow numbers in the West. The national average intensity of GHG emissions decreased by 42%, which gave just a 14% increase in the total GHG emissions of all dairy farms over the 50-yr period. The intensity of fossil energy use decreased by 54%, with the total for all farms decreasing by 9%. Water use related to milk production decreased in intensity by 28%, but due to the large increase in dairy production in the dry western regions that have a greater dependence on irrigated feed crops, total blue water use increased by 42%. Major pathways of nitrogen loss included ammonia volatilization, leaching, and denitrification, where total ammonia emissions related to US dairy farms increased by 29%, while leaching losses decreased by 39%, with little change in nitrous oxide emissions. Simulated nitrogen and phosphorus runoff losses totaled for all dairy farms decreased by 27% to 51% through more efficient fertilizer use, reduced tillage, and greater use of cover crops. Emissions of methane and reactive non-methane volatile organic compounds increased by 32% and 53%, respectively, due to greater use of long-term manure storage and silage stored in bunkers and piles. Although much progress has been made in improving production efficiency, continued improvements with new strategies and technologies are needed to meet the demand for dairy products and mitigate total environmental impacts, particularly in view of projected climate variability.

Association between ethylene oxide exposure and sex steroid hormone levels in male adults in the United States

Sex steroid hormones play important roles in maintaining our health systems, including reproductive function and developmental health. Ethylene oxide (EtO) is a reactive organic compound that is widely used in the gas sterilization of materials such as foods, spices, and medical devices. Previous studies have suggested that EtO exposure is associated with carcinogenic risk, neurotoxicity, and reproductive toxicity. However, no studies focusing on the relationship between EtO exposure and changes in sex steroid hormone levels have been performed in human. The present study investigated the association between blood EtO levels and serum sex steroid hormone levels in 1,635 adult men from the NHANES 2013-2016. Multivariate linear regression analyses, a positive correlation between blood EtO and total testosterone levels, and the testosterone to estradiol ratio. Moderate EtO exposure was associated with a decrease in estradiol levels, but no relationship was found at the highest exposure range. No significant associations were observed between EtO exposure and free testosterone, bioavailable testosterone, or sex hormone-binding globulin levels. These findings suggest EtO exposure could impact human sex steroid hormone production, although analysis in females and further verification through prospective studies should be performed.

Study of thermal state, water absorption and strength properties of composite polymerpolymer binders

In this article, in order to improve the heat-water resistance and strength properties, the modification of urea-formal- dehyde polymeric materials is considered by introducing melamine and acrylonitic resins and reactive compounds into their composition. Shown by identifying the optimal ratios of urea-formaldehyde, melamine and acrylonitrile resins and the corresponding reactive compounds in increasing the heat-water resistance and shear strength of adhesive joints based on them, replacing expensive phenol-formaldehyde resins used in gluing basalt fibrous masses in the production of build- ing heat-insulating sheet materials.

Novel Derivatives of Phenylisoxazole‐3/5‐Carbaldehyde Semicarbazone: Synthesis, Characterization, and Computational Studies

Six novel phenylisoxazole semicarbazone derivatives 1–6 were synthesized by reaction of the corresponding phenylisoxazole‐3/5‐carbaldehyde derivatives with semicarbazide hydrochloride. The synthesized compounds were characterized by ESI‐MS, FT‐IR, and NMR (1H, 13C) spectroscopic techniques. The two‐dimensional 1H‐1H NOESY NMR (in acetone‐d6) data revealed that compound 1 exists in the E isomeric form. The computational study of the energetic, structural, and electronic properties, carried out at B3LYP/6‐311G++(d,p) level of theory, showed that the most stable conformer for the all synthesized compounds, in both gas and liquid (acetone and DMSO) phases, has a cisE geometrical configuration. This evidence found is in good agreement with the spectrometric results. The geometrical parameters, frontier molecular orbital (FMO), molecular electrostatic potential (MEP), Mulliken atomic charges, and natural bonding orbital (NBO) analysis were also performed at the same level of theory. Taking into account the relative enthalpies ΔH computed, we can establish for tautomeric structures of each of the compounds, the following stability order: I (cisE) &gt; II (E′E) &gt; III (cisE). The MEP descriptors indicate that the oxygen atom of the carbonyl group C=O is susceptible to electrophilic attack, while the hydrogen atoms of the amide and hydrazone fragments are sensitive to nucleophilic attack. The calculated HOMO‐LUMO gap energies Eg indicate that 5 (in gas phase) and 6 (in liquid phase) are the most stable and less reactive compounds, while 1 is the less stable and the most reactive compound. From the NBO analysis, it becomes evident that the presence of the hydrazone fragment produces stabilizing effects due to hyperconjugative interactions.

Preparation of polycrotonic aldehyde

Croton aldehyde (2-butenal) is a reactive compound. NaOH and, in the second experiment, KOH were used to get polycrotonic aldehyde. The dependence of alkali concentration and amount of water on the yield of polymerization products was revealed. It was found that the got compounds are not homogeneous, differ in their solubility, composition and physicochemical properties.

Selectively lighting up glyoxal in living cells using an o-phenylenediamine fused hemicyanine.

Glyoxal (GL) is a reactive α-dicarbonyl compound generated from glycated proteins in the Maillard reaction. It has attracted particular attention over the past few years because of its possible clinical significance in chronic and age-related diseases. In this work, a reaction-based red emission fluorescent probe GL1 has been synthesized successfully by grafting an alkyl group onto an amino group to regulate its selectivity for GL. Under physiological conditions, the fluorescence intensity of GL1 at 640 nm obviously increased with the increase of GL concentration, and it exhibited high selectivity for GL over other reactive carbonyl compounds, as well as a lower detection limit (0.021 μM) and a larger Stokes shift (112 nm). At the same time, GL1 can selectively accumulate in mitochondria and can be used to detect exogenous and endogenous GL in living cells with low cytotoxicity.

Asymmetric electrophilic functionalization of amino-substituted heteroaromatic compounds: a convenient tool for the enantioselective synthesis of nitrogen heterocycles.

The catalytic asymmetric electrophilic functionalization of the less reactive N-heteroaromatic compounds has been reported using the approach of the introduction of an exocyclic amino substituent. This strategy has allowed enantioselective Friedel-Crafts alkylation in pyrazoles, isoxazoles and isothiazoles, as well as in aminoindoles, aminobenzofurans and aminobenzothiophenes. Several stereoselective methods have been used for the 1,4-addition or 1,2-addition of these heteroaromatic compounds to different electrophiles employing organocatalysts or chiral metal complexes. The activating exocyclic amino substituent has also been used as a nucleophile in tandem reactions, including formal cycloadditions ([3+2] and [3+3]), for the synthesis of highly functionalized chiral nitrogen heterocycles.