Mild Conditions Research Articles

Photo‐induced three‐component reaction for the construction of α‐tertiary amino acid derivatives

The synthesis of α‐tertiary amino acids (ATAAs), which are pivotal components in natural metabolism and pharmaceutical innovation, continues to attract significant research interest. Despite substantial advancements, the pursuit of a facile, versatile, and resource‐efficient methodology remains an area of active development. In this work, we introduce a visible light‐triggered three‐component reaction involving readily available nitrosoarenes, N‐acyl pyrazoles, and allyl or (bromomethyl)benzenes under mild conditions. This approach enables the straightforward assembly of a wide array of ATAA derivatives (41 examples) in commendably high yields (up to 89%). Mechanistic investigations elucidate that the reaction proceeds through a dehydration condensation between nitrosoarenes and N‐acyl pyrazoles to generate ketimine intermediates. This is followed by a light‐driven halogen atom transfer (XAT) process and a radical addition, culminating in the formation of the desired products. The approach showcases excellent functional group compatibility and late‐stage derivatization potential, offering new insights and avenues for the synthesis of ATAA analogs.

Synthesis of Hemiindigo Derivatives via a Gold‐Catalyzed Intramolecular Cyclization Strategy

We described a gold‐catalyzed synthesis of Z‐hemiindigo frameworks from ortho‐propynol phenyl azides via the β‐hydroxy‐α‐imino gold carbene intermediates. The intermediates are trapped by water or acetone and then subsequently undergo enol tautomerization and dehydration, or release of acetone. The reaction has the advantage of being able to be carried out under mild conditions and on a gram‐scale. Importantly, this method enables a simple and efficient synthesis of the special hemiindigo derivatives for the development of environmentally sensitive photoswitches in biological systems.

Platinum(II) acetimino cyclometalated complexes derived from room temperature ammonia activation

Two Pt(II) rollover cyclometalated complexes, [Pt(bpyPh‐H)(DMSO)Me] (1) and [Pt(bpyPh‐H)(DMSO)Cl] (2), where bpyPh‐H is the C3‐deprotonated 6‐phenyl‐2,2’‐bipyridine, were reacted with aqueous ammonia in acetone at room temperature. In the case of the electron‐poor complex 2 simple substitution of DMSO gave the amino complex [Pt(bpyPh‐H)(NH3)Cl] (4), whereas the electron‐rich complex 1 produced the rare acetimine complex [Pt(bpyPh‐H)(HN=CMe2)Me] (3), stable both in solution and in the solid state. The result is noteworthy, as the condensation product of acetone and ammonia, acetimine, is not stable under mild conditions. The reaction likely requires a Pt(II) electron‐rich complex and the presence of a carbon donor in trans position. An analogous reaction occurs with methylamine, allowing the synthesis of the secondary imine complex [Pt(bpyPh‐H)(MeN=CMe2)Me], 5. Starting from this finding a series of cyclometalated acetimine complexes [Pt(N^C)(HN=CMe2)Me] were isolated and characterized with other classical and rollover cyclometalated ligands with an array of different electronic and steric properties, indicating a possible extension of the reaction to various cyclometalated ligands. A preliminary study on the antimicrobial and antitumor properties of complex 3, taken as a model for this class, showed no significant effects against Gram‐positive, Gram‐negative bacteria, or yeasts, but found activity in vitro against HT29 colon cancer cell line.

Global Inference and Test for Eigensystems of Imaging Data Over Complicated Domains

A nonparametric approach for analyzing eigensystems of image data over a complex domain is novelly developed. The proposed estimators, which are based on bivariate splines, have both oracle efficiency of O p ( n − 1 / 2 ) , meaning they are asymptotically indistinguishable from estimators computed with true trajectories, and computational efficiency with more convenient spectrum decomposition forms. Under mild conditions, we derive consistency and weak convergence of our proposed estimators, which can be used to construct confidence intervals and simultaneous confidence corridors for any individual eigenvalue and eigenfunction, as well as design uniform inference procedures for eigensystems with a diverging number of components. In addition, we extend our method to two-sample test problems. Extensive simulation results provide strong support for the asymptotic theory, and the procedures are applied to two potential seawater temperature data sets to demonstrate its validity.

Selective reductive conversion of CO2 to CH2-bridged compounds by using a Fe-functionalized graphene oxide-based catalyst

Anthropogenic climate change drastically affects our planet, with CO2 being the most critical gaseous driver. Despite the existing carbon dioxide capture and transformation, there is much need for innovative carbon dioxide hydrogenation catalysts with excellent selectivity. Here, we present a fast, effective, and sustainable route for coupling diverse alcohols, amines and amides with CO2 via heterogenization of a natural metal-based homogeneous catalyst through decorating on functionalized graphene oxide (GO). Combined synthetic, experimental, and theoretical studies unravel mechanistic routes to convergent 4‑electron reduction of CO2 under mild conditions. We successfully replace the toxic and expensive ruthenium species with inexpensive, ubiquitously available and recyclable iron. This iron-based functionalized graphene oxide (denoted as Fe@GO-EDA, where EDA represents ethylenediamine) functions as an efficient catalyst for the selective conversion of CO2 into a formaldehyde oxidation level, thus opening the door for interesting molecular structures using CO2 as a C1 source. Overall, this work describes an intriguing heterogeneous platform for the selective synthesis of valuable methylene-bridged compounds via 4‑electron reduction of CO2.

Photocatalyst‐Free Chiral Phosphoric Acid‐Catalyzed Enantioselective Minisci‐Type Alkylation of N‐Heteroarenes

In this study, we present an efficient radical approach for the enantioselective Minisci‐type alkylation of N‐heteroarenes, using chiral phosphoric acid (CPA) as a catalyst under mild conditions, without the need for metals, photocatalysts, and other additives. Prochiral α‐aminoalkyl radicals generated from RAEs were successfully introduced to N‐heteroarene derivatives, including pyridine, quinoline, and isoquinoline, resulting in a range of valuable chiral alkylated N‐heteroarenes with secondary amines in high yields and good to excellent enantioselectivities (up to 98% ee). The chiral phosphoric acid catalyst not only activates the substrate and induces asymmetry but also facilitates essential electron transfer processes.

Cu(II)-tyrosinase enzyme catalyst mediated synthesis of mosquito larvicidal active pyrazolidine-3,5-dione derivatives with molecular docking studies and their ichthyotoxicity analysis

The objective of this study was to develop pyrazolidine-3,5-dione derivatives with potential as environmentally friendly pesticides for pest control, specifically focusing on their efficacy as larvicidal agents. A novel one-pot synthesis of multicomponent pyrazolidine-3,5-dione derivatives (1a-m) was accomplished via the grindstone method using Cu(II)tyrosinase enzyme as a catalyst under mild reaction conditions, yielding 84%–96%. The synthesised derivatives (1a-m) were characterized using various spectroscopic methods (mass spectrometry, elemental analysis, FT-IR, and 1H and 13C NMR). NMR characterisation using DMSO-d6 as a solvent. The larvicidal and antifeedant activities of the synthesised compounds were screened and in silico computational studies were performed. The larvicidal activity against Culex quinquefasciatus and antifeedant activity against Oreochromis mossambicus were evaluated. Among the synthesised compounds, compound 1c demonstrated superior efficacy (LD50: 9.7 μg/mL) against C. quinquefasciatus compared to permethrin (LD50: 17.1 μg/mL). Regarding antifeedant activity, compounds 1a, 1e, 1f, 1j, and 1k exhibited 100% mortality at 100 μg/mL. Molecular docking analysis was performed to assess the binding capacity of a mosquito odorant-binding protein (3OGN) from Culex quinquefasciatus to compound 1c. The results revealed that compound 1c had a docking score of -10.4 kcal/mol, surpassing that of standard permethrin (-9.5 kcal/mol). Furthermore, DFT calculations were conducted to acquire theoretical data aligned with the experimental FT-IR results. According to experimental research, compound 1c demonstrates promising larvicidal activity against mosquito larvae of C. quinquefasciatus.

Ligand-to-Metal Charge Transfer (LMCT) Catalysis: Harnessing Simple Cerium Catalysts for Selective Functionalization of Inert C-H and C-C Bonds.

ConspectusChemists have long pursued harnessing light energy and photoexcitation processes for synthetic transformations. Ligand-to-metal charge transfer (LMCT) in high-valent metal complexes often triggers bond homolysis, generating oxidized ligand-centered radicals and reduced metal centers. While photoinduced oxidative activations can be enabled, this process, typically seen as photochemical decomposition, remains underexplored in catalytic applications. To mitigate decomposition during LMCT excitation, we developed a catalytic cycle integrating in situ coordination, LMCT, and ligand homolysis to activate ligated alcohols transiently into alkoxy radicals. This catalytic approach leverages Ce(IV) LMCT excitation and highly reactive alkoxy radical intermediates for selective functionalizations of C(sp3)-H and C(sp3)-C(sp3) bonds under mild conditions. In this Account, we discuss these advancements, highlighting the practical utility of cost-effective cerium salts as catalysts and their potential to develop innovative transformations, addressing long-standing synthetic challenges.Selective functionalization of chemically inert C(sp3)-H bonds has long posed a significant challenge. We first detail our research using LMCT-enabled alkoxy radical-mediated hydrogen atom transfer (HAT) processes for selective C(sp3)-H functionalizations. Using readily available CeCl3, we established a general protocol for employing free alcohols in the Barton reaction. By integrating LMCT and HAT catalysis, we introduced a selective photocatalytic strategy for functionalizing feedstock alkanes, converting gaseous hydrocarbons into valuable products. Employing simple cerium salts like Ce(OTf)3 and CeCl3, we achieved selective C-H amination of methane and ethane at ambient temperature, achieving turnover numbers of 2900 and 9700, respectively. This catalytic manifold has been further exploited to address the site-selectivity challenge in the C-H functionalization of linear alkanes. The use of methanol as a cocatalyst enabled preferential functionalization of the most electron-rich sites, achieving a high intrinsic selectivity over 12:1 of secondary vs primary sites in pentane and hexane.Next, we discuss the catalytic utilization of alkoxy-radical-mediated β-scission, a frequently encountered side reaction in HAT transformations, for selective cleavage and functionalization of C-C bonds. The versatility of the LMCT catalytic platform facilitates the generation of alkoxy radicals from various free alcohols. In our initial demonstration of LMCT-enabled C(sp3)-C(sp3) bond activation, we developed a cerium-catalyzed ring-opening and amination of cycloalkanols, providing an effective protocol for cleaving unstrained C-C bonds. This strategy has been successfully applied to various radical cross-coupling processes, leading to innovative transformations such as ring expansions of cycloalkanols, dehydroxymethylative alkylation, amination, alkenylation, and ring expansions of cyclic ketones. These results highlight the synthetic potential of employing LMCT-mediated β-scission and ubiquitous C-C bonds as unconventional functional handles for generating molecular complexity.Lastly, we delve into our mechanistic investigations. Beyond the catalytic application of Ce(IV) LMCT in various transformations, we have undertaken comprehensive mechanistic studies. These investigations encompass characterization of Ce(IV) alkoxide complexes to elucidate their structures, evaluation of their photoactivity and selectivity in radical generation, and elucidation of kinetic pathways associated with transient LMCT excited states. Our research has revealed ultrafast bond homolysis, back electron transfer, and the selectivity of heteroleptic complexes in homolysis, providing crucial insights for advancing LMCT catalysis.

A base-promoted synthesis of 3,4-dihydro-2(1H)-quinazolinones

Abstract A convenient and concise base-promoted synthesis of 3,4-dihydro-2(1H)-quinazolinones and multi-membered cyclic ureas has been developed. In the presence of tBuOK, a variety of 3,4-dihydro-2(1H)-quinazolinones as well as the N-arylated five-, six- and nine-membered cyclic ureas were readily synthesized under mild conditions. This method offers an alternative synthesis toolkit towards cyclic ureas.

Influences of Salt Stress on Cotton Metabolism and Its Consequential Effects on the Development and Fecundity of Aphis gossypii Glover

The degree of global soil salinization is gradually deepening, which will inevitably affect agricultural ecology. It has been found that salt stress induces the resistance of host plants to phytophagous pests. However, little is known about the effects of salt-stressed cotton plants on the fitness of cotton aphids (Aphis gossypii Glover). In this study, we investigated the differences between cotton metabolomes under mild (75 mM NaCl) and moderate (150 mM NaCl) salinity conditions and their effects on the fitness of cotton aphids. The results showed that 49 metabolites exhibited significant upregulation, while 86 metabolites were downregulated, with the increasing NaCl concentration. The duration of nymphal aphids under 150 mM NaCl significantly extended to 6.31 days when compared with the control (0 mM NaCl, 4.10 days). Meanwhile, the longevity of adult aphids decreased significantly under 75 and 150 mM NaCl, with an average of 10.38 days (0 mM NaCl) reduced to 8.55 and 4.89 days, respectively. Additionally, the total reproduction number of single females decreased from 31.31 (0 mM NaCl) to 21.13 (75 mM NaCl) and 10.75 (150 mM NaCl), whereas the survival rate of aphids decreased from 81.25% (0 mM NaCl) to 56.25% (75 mM NaCl) and 34.38% (150 mM NaCl) on the 12th day. These results support the hypothesis that plants growing under salt stress are better defended against herbivores. Furthermore, 49 differential metabolites were found to be negatively correlated with the longevity and fecundity of adult aphids, while 86 different metabolites showed the opposite trend. These results provide insights into the occurrence and control of cotton aphids amidst the escalating issue of secondary salinization.

Microwave and ultrasound-assisted green protocols for 5-methylthiazole induced Betti bases: molecular docking, in-silico pharmacokinetics, and anticancer activity studies

ABSTRACT Herein, we describe an efficient one-pot three-component microwave and ultrasound-endorsed approaches for synthesizing distinct 5-methylthiazole induced Betti bases (5-methyl-thiazol-2-ylamino-aryl-benzylnapthols) employing silica sulfuric acid (SSA, silica-OSO3H) as an active heterogeneous acid catalyst. The title compounds produced in good yields (86–95%) from naphthalen-2-ol, 5-methylthiazol-2-amine, and assorted aryl aldehydes; and structurally characterized by spectral and elemental analyses. A comprehensive comparative study of conventional, ultrasonic, and microwave-irradiated synthetic routes has been achieved by optimizing various reaction parameters. These new protocols provide several advantages, including the use of an inexpensive, non-toxic, and reusable catalyst. Additionally, they benefit from mild reaction conditions, short reaction times, and simple workup and purification procedures, thereby increasing their practicality. Furthermore, the synthesized compounds were evaluated for their anticancer potency against A-549 (lung cancer) and A-498 (kidney cancer) cell lines, with scaffold IVa demonstrating excellent (GI50 < 10 µg/mL) inhibitory activity against A-549. Additionally, molecular docking was performed to investigate potential binding interactions between ligands and proteins. Scaffold IVa exhibited the best docking with cancerous target proteins 1M17 (−8.9 kcal/mol) and 1M14 (−7.2 kcal/mol), thereby supporting our bio-activity studies.

Synthesis of Tetrasubstituted Enamines Using Secondary Amines and In Situ-Generated Allenes from Nitrocyclopropanes.

A novel reaction of cyclic and acyclic secondary amines with in situ-generated allene intermediate species from nitro-substituted donor-acceptor cyclopropanes is reported. In the presence of a simple inorganic base, NaOH, tetrasubstituted enamine derivatives can be obtained in moderate to excellent yields. The reaction is operationally easy, features mild reaction conditions and simple inorganic bases, and is free of transition metals.

Laccase-mediated chemoselective C-4 arylation of 5-aminopyrazoles.

Chemoselective arylation of 5-aminopyrazoles was performed through oxidative formation of orthoquinones from catechols catalyzed by Myceliophthora thermophila laccase (Novozym 51003), and subsequently nucleophilic attack of 5-aminopyrazole to the catechol intermediates. The C-4 arylated products were obtained under extremely mild conditions without the need for amine protection or halogenation of the substrates. From this method, 10 derivatives with moderate to good efficiency (42-94%) were prepared.

Statistical inference for the first-order autoregressive process with the fractional Gaussian noise

While the statistical inference of first-order autoregressive processes driven by independent and identically distributed noises has a long history, the statistical analysis for first-order autoregressive processes driven by dependent noises is more recent. This paper considers the problem of estimating all the unknown parameters in first-order autoregressive processes driven by the fractional Gaussian noise, which is a self-similar stochastic process used to model persistent or anti-persistent dependency structures in observed time series. The estimation procedure is built upon the marriage of the log-periodogram regression and the method of moments. The usual asymptotic properties, including consistency and asymptotic normality, are established under some mild conditions. Monte Carlo simulations are performed to demonstrate the feasibility and effectiveness of the proposed method. Finally, the estimation methods are applied to model some realized volatility time series, where we find that the realized volatility is rough. Moreover, the proposed model is compared with some alternative models, including the first-order autoregressive process driven by the standard Gaussian noise, the heterogeneous autoregression model with lag structure (1,5,21) (HAR(1,5,21)), the autoregressive fractionally integrated moving average model (ARFIMA(1,d,0)) and the scaled fractional Brownian motion, in forecasting the logarithmic realized volatility.

Recent Advances in Visible‐Light‐Mediated Synthesis of Phosphorylated Heterocycles

Organophosphorus compounds, especially phosphorylated heterocycles, are gaining increasing attention in the fields of materials science, pharmaceuticals, and agrochemistry due to their excellent biological activities. Consequently, the exploration of green and efficient methods for the synthesis of phosphorylated heterocycles has garnered significant interest from organic chemists. In recent years, visible light‐induced photoredox‐catalyzed organic synthesis has made substantial progress in the field of phosphorylation reaction since its eco‐friendly and mild conditions. This review summarizes the advance of the past five years in the visible‐light‐mediated synthesis of phosphorylated heterocycles using phosphine oxides as precursors through P‐centered radical addition, cross‐couping, and cyclization reactions.

BPBSBDM as an influential Brønsted acidic ionic liquid catalyst in preparing bis(pyrazolyl)methanes under mild conditions

BPBSBDM as an influential Brønsted acidic ionic liquid catalyst in preparing bis(pyrazolyl)methanes under mild conditions

Electrochemical Hydrogenation of Quinoline Enabled by Cu0‐Cu+ Dual Sites Coupled with Efficient Biomass Valorization in Aqueous Solution

AbstractThe hydrogenation of nitrogen‐containing heterocyclic precursors in aqueous medium is challenging, especially at ambient temperature and pressure. Electrochemical hydrogenation (ECH) of quinoline to 1,2,3,4‐tetrahydroquinoline (THQ) at mild conditions using water as the hydrogen source is demonstrated with splendid activity on a Cu‐based nonprecicous catalyst. The yield of THQ is up to ≈100% with ≈100% selectivity at −1.275 V vs Hg/HgO. The real active sites and key intermediates are deciphered, where the Lewis acid‐base sites on the heterointerface of Cu/Cu2O are beneficial to the quinoline adsorption in a dual‐site coordination configuration and water dissociation to afford H*. The presence of Cu0 plays a vital role in inhibiting the binding of H*, which ensures good Faradaic efficiency. In addition, a novel co‐production system by coupling benzyl alcohol oxidation at the anode is established, achieving dual benefits in both energy utilization efficiency and economic benefits.

Hollow CoFe Oxide Prisms for Cross-Dehydrogenative Coupling Reactions of 1,2,3,4-Tetrahydroisoquinolines under Mild Conditions.

A three-dimensional hollow CoFe oxide prism catalyst was successfully prepared via a self-template strategy. This bimetallic oxide catalyst demonstrated excellent catalytic activity in cross-dehydrogenative coupling reactions of 1,2,3,4-tetrahydroisoquinolines under mild conditions compared to its monometallic oxide counterparts. A preliminary mechanistic investigation showed the involvement of reactive oxygen species, produced from molecular O2 by the active bimetallic oxide catalyst in the catalytic cycle.

Asymmetric Synthesis of Chiral Cyclopropanes from Vinyl Sulfoxonium Ylides Catalyzed by a Chiral-at-Metal Rh(III) Complex.

A chiral-at-metal Rh(III) complex-mediated [2+1] cyclization of vinyl sulfoxonium ylides with α,β-unsaturated 2,2-acylimidazoles has been demonstrated for the first time. This work provides a practical approach for assembling 1,2,3-trisubstituted chiral cyclopropane with alkyl structural units, which had advantages such as a wide range of substrates, good functional group tolerance, and mild reaction conditions. In addition, further amplification experiments and transformation of cycloaddition products were carried out to highlight the practicality of the method.

4+2] Cycloaddition Mediated Stereoselective Synthesis of Tetrahydro‐1H‐Isobenzofuro Chromene Dione Derivatives: Antibacterial Evaluation and Molecular Docking Investigation

AbstractAn efficient stereoselective synthesis of tetrahydro‐1H‐isobenzofuro[4,5‐c]chromene‐1,3(3aH)‐dione derivatives were achieved through a novel [4+2] cycloaddition reaction of 4‐styryl‐2H‐chromenes with cheaply available maleic anhydride. A series of new tetrahydro‐1H‐isobenzofuro[4,5‐c]chromene‐1,3(3aH)‐dione derivatives 21(a–p) were synthesized in good to excellent yield under mild reaction condition with no chromatographic purification. In this reaction, the generation of four new consecutive stereogenic centers were determined by single crystal X‐ray analysis. All the synthesized compounds were investigated further in silico and in vitro for antibacterial activities using two bacterial strain of DNA gyrase. Compounds 21 b and 21 j showed excellent docking score −9.3 kCal/mol and −8.6 kCal/mol with gram negative bacterial strain Escherichia coli (E. coli) with protein data bank (PDB ID) 3G7E. Out of all the tested molecules, 21 b and 21 j displayed good results with minimum inhibitory concentration 10 μg/ml, 10 μg/ml against the bacterial strain Escherichia coli(E. coli) and 10 μg/ml, 20 μg/ml against Staphylococcus aureus (S. aureus) respectively.