Good Yields Research Articles

Optimization and Effect of Substituents on the Transformation of 3-(Substituted acetoxy)azetidin-2-ones to Chiral 3-Hydroxyazetidin-2-ones, Molecular Docking and Enantiomeric Excess Determination

Abstract: The enantioselective synthesis of chiral cis-3-hydroxyazetidin-2-ones mediated by Porcine Pancreatic Lipase (PPL) via hydrolysis of cis-3-(chloro acetoxy) azetidin-2-ones in the presence of a phosphate buffer (0.1M, pH = 7.2) in acetonitrile at a temperature range of 25-35 °C was optimized. Under the optimized reaction conditions, the influence of various electron withdrawing/donating/neutral groups on ester functionality of cis-3-(substituted acetoxy)azetidin-2- ones towards hydrolysis was extensively studied, and the bromoacetoxy, propanyloxy, and formyloxy groups provided moderate to good yields of 90%, 91%, and 81%, respectively. Moreover, the chiral cis-3-hydroxyazetidin-2-ones underwent acetylation, and their enantiomeric excess was assessed using the 1H NMR technique, employing chiral shift reagents. To gain insights into the active sites of the biocatalyst, molecular docking studies of compounds 5(a-i) with pancreatic lipase (PDB ID: 1LBS) were carried out. Additionally, the proposed interaction of substituents with the biocatalyst established the absolute stereochemistry of the target chiral cis-3-hydroxyazetidin-2-ones using Seebach's model in comparison to Jone's models.

Genetic assessment of diverse rice germplasm for yield-related and stress tolerance traits

AbstractThe development of stress-resistant crops without compromising their yield and nutritional quality is one of the major challenges in plant biology. Plant breeders have made considerable effort in developing cultivars with high yield and tolerance to biotic and abiotic stresses. This research aimed to evaluate pre-breeding resources for favorable genes conferring good yield and resistance to biotic and abiotic stresses for rice varietal improvement. Two hundred forty diverse rice cultivars from top countries with which the United States imports and exports rice were selected from the Germplasm Resource Information Network (GRIN) collection, and these were characterized using molecular markers for various desirable traits. Among the cultivars, 16 were used as checks. The genes of various traits evaluated were grain number (Gn1a), panicle weight (WFP), cold stress tolerance (qSCT-11 and qCTS-12), anaerobic germination (AG1 and AG2), rice blast disease resistance (PiB, Pi-ta, Ptr, and Piz), wide compatibility (S5-n), and restoring ability (Rf4). Out of these 240 accessions, 192 have the Gn1a gene, 168 possess the qSCT-11 cold tolerance gene, 139 carry the Rf4 gene, 152 have the qCTS12 cold tolerance gene, 87 have blast resistance genes, and 44 possess the WC gene. None of the 240 accessions possess the WFP (Wealthy Farmer’s Panicle) gene. The selections with favorable genes can be used by breeders as potential donor parents for varietal improvement programs to produce new and promising cultivars with desired specific traits that may contribute towards alleviating global issues related to food security.

Ligand-Enabled C6-Selective C-H Arylation of Pyrrolo[2,3-d] Pyrimidine Derivatives with Pd Catalysts: An Approach to the Synthesis of EGFR Inhibitor AEE-788.

Herein, we report the Pd(II)-catalyzed direct C-H arylation of pyrrolo[2,3-d]pyrimidine derivatives with aryl iodides, which is enabled by bidentate pyridine-pyridine ligands. A range of aryl iodides proved to be suitable coupling partners affording the desired products in good yields with high levels of C6 selectivity. This protocol features good tolerance of reactive functional groups, mild reaction conditions, and a simple reaction system, which provides an expeditious route to an essential class of 6-arylpyrrolo[2,3-d]pyrimidines frequently found in bioactive compounds, and provides a step-economical access to the second-generation EGFR inhibitor AEE-788.

Rapid Synthesis of Peptides Mediated by PPh3−I2

AbstractWe report a mild, operationally simple, convenient, and rapid method of peptide bond formation using triphenylphosphine and iodine. The developed protocol was utilized to couple coded, non‐coded, and challenging amino acids in 64–92 % yield. Sterically hindered α,α‐disubstituted amino acids, which are important constituents of natural peptides, were also coupled in good yield. Mild reaction conditions in open air produce peptide bonds in a short time (30 min) without racemization.

Structural Diversity of Sn(II) Phosphine Oxide Complexes with Weakly Coordinating Anions and Comparisons with Related Ge(II) and Pb(II) Species

A series of tin(II) triflate phosphine oxide complexes has been prepared from the reaction of Sn(OTf)2 (OTf‐ = [O3SCF3]‐ with various ratios of OPPh3, OPMe3 or dppmO2 (dppmO2 = Ph2(O)PCH2P(O)Ph2). The complexes [Sn(OPPh3)n][OTf]2 (n = 2, 3 or 4), [Sn(OPMe3)n][OTf]2 (n = 2 or 3) and [Sn(dppmO2)n][OTf]2 (n = 1 or 2) have been isolated in moderate to good yields. Selected germanium(II) and lead(II) analogues have been made for comparison, namely [Ge(OPPh3)n][OTf]2 (n = 2 or 3) and [Pb(OPR3)4][OTf]2 (R = Me, Ph). The effect of changing the weakly coordinating OTf‐ anion for the non‐coordinating [BArF]‐ anion was investigated through anion metathesis, furnishing the complexes [Sn(OPPh3)n][BArF]2 (n = 3 or 4) and [Ge(OPPh3)3][BArF]2. The isolated solids were characterised by 1H, 19F{1H}, 31P{1H} and IR spectroscopy and microanalysis. Crystal structures were obtained for all complexes except [Ge(OPPh3)2][OTf]2 and [Sn(OPPh3)3][BArF]2, allowing comparisons of the structural features of these divalent group 14 complexes down the group and as a function of coordination number, ligand sterics and electronics.

Mechanistic insights into the role of cyclodextrin in the regioselective radical CH trifluoromethylation of aromatic compounds.

The regioselective radical CH trifluoromethylation of aromatic compounds have been shown to proceed in good yield and high regioselectivity when cyclodextrin (CD) is present. Yet, the reaction mechanism and the role of CD during the reaction have remained obscure. To this end, here we performed density functional theory (DFT) calculations to the conformations obtained by semiempirical quantum mechanical molecular dynamics calculations to reveal the reaction mechanism and the role of CD in controlling regioselectivity. The results show that metal salt increases the yield but do not affect the regioselectivity, which we further confirmed by an experiment. In contrast, multiple CD-substrate complex conformations and reaction pathways were obtained, and CD was shown to contribute to improving the regioselectivity by stabilizing the intermediate state via encapsulation. The present study indicates that CDs can increase the regioselectivity by stabilizing the intermediate and product states while only marginally affecting the transition state.

Cyclopropanation of Aryl and Styryl Acetonitriles With Selenium‐Based Dielectrophiles

AbstractEfficient cyclopropanation reactions of aryl or styrylacetonitriles with vinyl selenones under mild conditions were described. By this approach, synthetically challenging 1‐vinylcyclopropane‐1‐carbonitriles were accessible in good yields. This methodology features the advantage of operational simplicity, broad substrate scope, good functional group tolerance, transition‐metal‐free conditions, mild temperature, and a high level of regio‐ and diastereo‐control.

Catalytic Enantioselective Electrophilic Difunctionalization of Unsaturated Sulfones.

An efficient protocol of enantioselective thiolative azidation of sulfone-tethered alkenes via a chiral chalcogenide catalyzed electrophilic reaction is disclosed. A series of enantioenriched sulfones bearing remote stereogenic centers was achieved with good yields and high enantioselectivities with linear unsaturated sulfones and cyclic unsaturated sulfones. Mechanistic studies revealed the importance of the sulfone group in the improvement of the reactivity and enantioselectivity of the reaction.

CVO/TiO2 Heterojunction Photocatalyst for the Synthesis of Arylamines via Oxidative Aromatization of Amines and Cyclohexenones

A novel CVO/TiO2 heterojunction material has been prepared and used to catalyze the oxidative aromatization of amines and cyclohexenones under visible light irradiation, avoiding the use of noble metal catalysts and providing an environmentally friendly alternative for the synthesis of aromatic amines. The catalytic reaction uses oxygen as the final oxidant and provides good yields over a wide range of substrates. Notably, the recyclable heterogeneous semiconductor photocatalyst can be readily recovered and reused for at least four cycles. In addition, several biologically active molecules were successfully synthesized using the photocatalytic method.

Enantioselective Synthesis of Sterically Hindered α‐Allyl‐α‐Aryl Lactams via Palladium‐Catalysed Decarboxylative Asymmetric Allylic Alkylation

AbstractThe Pd‐catalysed decarboxylative asymmetric allylic alkylation (DAAA) of sterically hindered α‐aryl,β‐amido allyl ester lactams has been developed. The key step in the synthesis of a range of α‐aryl lactam substrates for catalysis was a Pb‐mediated α‐arylation of a β‐amido allyl ester affording 14 novel examples of α‐aryl‐β‐amido allyl ester lactams in good yields (up to 80 %). The Pd‐catalysed DAAA was optimised with the 2,4,6‐trimethoxyphenyl‐containing substrate. Using (S,S)‐DACH‐phenyl Trost as the optimal chiral ligand, enantioselectivities of up to 82 % ee were obtained. A substrate scope of 11 examples of α‐aryl‐β‐amido allyl ester lactams showed that products containing the di‐ortho‐methoxy‐substituted phenyls and naphthyl groups gave rise to the highest ees, whereas products not bearing this substitution pattern showed lower enantioselectivities (<60 % ee). Transition states to rationalise the observed stereochemical outcome are proposed.

Palladium complexes of N,O‐bidentate ligands bearing N‐oxide units as simple and efficient catalysts for Suzuki–Miyaura reaction of aryl halides with arylboronic acids

Palladium‐catalyzed Suzuki–Miyaura reaction is an important synthetic strategy for the synthesis of biaryl compounds. This work describes that palladium complexes with N,O‐bidentate ligands bearing N‐oxide units from cyclic secondary amines were used as highly efficient catalysts for Suzuki–Miyaura reactions of aryl halides with arylboronic acids. The reaction exhibited good functional group compatibility, high yields, and mild conditions. More importantly, these N,O‐coordinated palladium complexes could be easily prepared and displayed excellent catalytic performance for this classic Csp2–Csp2 coupling reaction in very short time.

A new nickel-based δ-isomer Anderson-type polyoxometalates: Synthesis, crystal structure and catalytic activity in 1,2,3-triazoles production

In this study, we present a novel organic hybrid Ni-based δ-isomer of Anderson-type polyoxometalates (POMs), namely, δ-[C6H12Mo6N2NiO24]4− (1), as an efficient catalyst for the cycloaddition reaction between alkynes, halides, and sodium azide. Synthesis of the catalyst was performed using a facile one-pot method followed by characterization using single crystal, powder XRD, SEM, and FT-IR techniques. After optimizing reaction conditions for a model reaction (T = 80 °C, time = 6 h, and solvent = 2 mL H2O), the catalytic activity of this compound was examined for the preparation of diversely substituted 1,2,3-triazoles under ambient atmospheric and additive-free conditions, achieving moderate to good yields. Catalyst 1 could reuse up to four sequential cycles without significant loss in its catalytic activity. Additionally, the true heterogeneity of the catalyst was determined by the hot-filtration test.

Lewis acid mediated allylation of vinyl diazonium ions by allylstannanes.

The Lewis acid mediated reaction of allyltributylstannane compounds with β-hydroxy-α-diazo carbonyls gives β-allyl-α-diazo carbonyl products in good yields. This reaction proceeds via a vinyl diazonium ion intermediate which is intercepted by the allylstannane nucleophile. Importantly, the diazo functional group is retained over the course of the reaction to give diazo-containing scaffolds with increased molecular complexity. Methallyltrimethylsilane also serves as a functional allyl transfer reagent in this reaction.

Copper-Catalyzed [4+1+1] Annulation of Ammonium Salts and Anthranils: Synthesis of 2,3-Diaroylquinolines.

A copper(I)-catalyzed protocol is developed for the synthesis of various 2,3-diaroylquinolines starting from achiral ammonium salts and anthranils through [4+1+1] annulation. Using copper(I) chloride as the sole catalyst, this reaction is featured with easily available starting materials, broad substrate scope, good yields and simple reaction conditions.

Iron(I) Complex Bearing an Open-Shell Diazenido Ligand.

Low-valent transition-metal diazenido species are important intermediates in transition-metal-mediated dinitrogen reduction reactions. Isolable complexes of the type unanimously feature closed-shell diazenido ligands. Those bearing open-shell diazenido ligands have remained elusive. Herein, we report the synthesis, characterization, and reactivity of a d7 iron(I) complex featuring an open-shell silyldiazenido ligand, [(ICy)Fe(NNSiiPr3)(η2:η2-dvtms)] (1, ICy = 1,3-dicyclohexylimidazole-2-ylidene, dvtms = divinyltetramethyldisiloxane). Complex 1 is prepared in good yield by silylation of the iron(-I)-N2 complex [K(18-crown-6)][(ICy)Fe(N2)(η2:η2-dvtms)] with iPr3SiOTf and has been fully characterized by various spectroscopic methods. Theoretical studies, in combination with characterization data, established an S = 1/2 ground spin-state for 1 that can best be described as a quartet iron(I) center featuring an antiferromagnetically coupled triplet silyldiazenido ligand. The diazenido and alkene ligands in 1 are labile, as indicated by the facile disproportionation reaction of 1 at ambient temperature to transform into the iron(II) bis(diazenido) species [(ICy)(NNSiiPr3)2Fe(dvtms)Fe(NNSiiPr3)2(ICy)] (2) and the iron(0) species [(ICy)Fe(η2:η2-dvtms)] and also the alkene-exchange reaction of 1 with PhCH═CHBC8H14 to form [(ICy)Fe(NNSiiPr3)(η2-trans-PhCH═CHBC8H14)] (3). Complex 1 is light-sensitive. Upon photolysis, it undergoes a SiiPr3 radical-transfer reaction to yield [(ICy)Fe(σ:η2-MeCHSiMe2OSiMe2CH═CHSiiPr3)] (4) and N2. The reactions of 1 with the trityl radical and organic bromides yield iron(II) complexes, which indicates its reducing nature. Moreover, 1 is a weak hydrogen-atom abstractor, as indicated by its inertness toward HSi(SiMe3)3 and cyclohexa-1,4-diene and the low calculated N-H bond dissociation energy (48 kcal/mol) of its corresponding iron(II) iso-hydrazenido species.

Visible Light Photoredox-Catalyzed Formyl/Carboxylation of Activated Alkenes with Glyoxylic Acid Acetals and CO2.

A photoredox-catalyzed sequential α-formyl/carboxylation of alkenes with glyoxylic acid acetals and CO2 has been developed to afford a range of masked γ-formyl esters in good yields, which could be readily transformed into diverse compounds, such as γ-formyl ester, hemiacetal, and 1,4-diol. This reaction features mild conditions, readily available starting materials, and operational simplicity.

Radiosynthesis and Preclinical Evaluation of m-[18F]FET and [18F]FET-OMe as Novel [18F]FET Analogs for Brain Tumor Imaging.

O-([18F]Fluoroethyl)-l-tyrosine ([18F]FET) is actively transported into the brain and cancer cells by LAT1 and possibly other amino acid transporters, which enables brain tumor imaging by positron emission tomography (PET). However, tumor delivery of this probe in the presence of competing amino acids may be limited by a relatively low affinity for LAT1. The aim of the present work was to evaluate the meta-substituted [18F]FET analog m-[18F]FET and the methyl ester [18F]FET-OMe, which were designed to improve tumor delivery by altering the physicochemical, pharmacokinetic, and/or transport properties. Both tracers could be prepared with good radiochemical yields of 41-56% within 66-90 min. Preclinical evaluation with [18F]FET as a reference tracer demonstrated reduced in vitro uptake of [18F]FET-OMe by U87 glioblastoma cells and no advantage for in vivo tumor imaging. In contrast, m-[18F]FET showed significantly improved in vitro uptake and accelerated in vivo tumor accumulation in an orthotopic glioblastoma model. As such, our work identifies m-[18F]FET as a promising alternative to [18F]FET for brain tumor imaging that deserves further evaluation with regard to its transport properties and in vivo biodistribution.

An ambipolar PEDOT-perfluorinated porphyrin electropolymer: application as an active material in energy storage systems.

The development of functional organic materials is crucial for the advancement of various fields, such as optoelectronics, energy storage, sensing, and biomedicine. In this context, we successfully prepared a stable ambipolar perfluoroporphyrin-based polymeric film by electrochemical synthesis. Our strategy involved the synthesis of a novel tetra-pentafluorophenyl porphyrin covalently linked to four 3,4-ethylenedioxythiophene (EDOT) moieties. The resulting monomer, EDOT-TPPF16, was obtained through a straightforward synthetic approach with a good overall yield. The unique molecular structure of EDOT-TPPF16 serves a dual function, with EDOT moieties allowing electropolymerization for polymeric film formation, while the electron-acceptor porphyrin core enables electrochemical reduction and electron transport. The electrochemical polymerization permits the polymer (PEDOT-TPPF16) synthesis and film formation in a reproducible and controllable manner in one step at room temperature. Spectroelectrochemical experiments confirmed that the porphyrin retained its optoelectronic properties within the polymeric matrix after the electrochemical polymerization. The obtained polymeric material exhibited stable redox capabilities. Current charge-discharge cycles and electrochemical impedance spectroscopy of the electrochemically generated organic film demonstrated that the polymer could be applied as a promising active material in the development of supercapacitor energy storage devices.

22]Pentaphyrins(2.0.1.1.0) Displaying N-Fusion, Pyrrole-Rearrangement, and Dimerization Reactions Upon Oxidation and Metalation.

Exploration of expanded porphyrins with unprecedented reactivities has remained important. Here [22]pentaphyrins(2.0.1.1.0) were synthesized as a constitutional isomer of sapphyrin by acid-catalyzed cyclization of 1,14-dibromo-5,10-diaryltripyrrin with 1,2-di(pyrro-2-ly)ethenes. These pentaphyrins display roughly planar structures and varying aromaticities depending upon the vinylene structures. The 19,20-ditolyl pentaphyrin gave an N-fused product and an unprecedented pyrrole-rearranged product, depending upon the oxidation conditions. Remarkably, upon the metalation with CuCl, the N-fused product and the pyrrole-rearranged product afforded an inner b-b coupled face-to-face CuII complex dimer and an outer b-b coupled lateral CuII complex dimer, respectively, in fairly good yields. Further, [22]pentaphyrin(2.0.1.1.0) fused with a NiII porphyrin was effectively dimerized upon oxidation with MnO2 to give a 16-16' directly linked dl-dimer.

Synthesis of Biindene Derivatives via Pd-Catalyzed Alkene Difunctionalization Reactions.

The palladium-catalyzed cross-coupling of 2-allylphenyl triflate and related electrophiles with substituted indenes affords biindene derivatives in moderate to good yields with high selectivity for thermodynamically preferred alkene isomers. The transformations involve alkene nucleopalladation with indenyl anions, and we also demonstrate that 2-allylphenyl triflates can be transformed to indenes under similar conditions. The scope of this transformation, along with the mechanism of formation of both indene and biindene products, is described.