Experiment and Computational Study on Pd-Catalyzed Methoxyiminoacyl-Directed γ-Alkoxylation of Alkylamides.

The direct alkoxylation of amides has been accomplished via methoxyiminoacyl (MIA)-mediated Pd-catalyzed C-H functionalization. A diverse array of alkylamide substrates is amenable to this protocol, providing γ-C(sp3)-alkoxylation of alkylamide derivatives with good to high efficiency. Two aspects of the research were completed to explore the reaction mechanism. On the one hand, the result of the kinetic isotopic effect experiment and control experiment indicated that reductive elimination is a rate-limiting step. On the other hand, density functional theory calculations demonstrated that a concerted Sn2 reductive elimination mechanism pathway is prior. Finally, the MIA group could be efficiently hydrogenated and protected in a one-pot procedure, which provides a short synthetic route to γ-methoxy amino acid derivatives.

Methionine-Derived Organogels as Lubricant Additives Enhance the Continuity of the Oil Film through Dynamic Self-Healing Assembly.

(S)-2-((1-(Hexadecylamino)-4-(methylthio)-1-oxobutan-2-yl)carbamoyl)benzoic acid (HMTA) was efficiently synthesized and successfully applied as an additive to several types of blank lubricant oils. Initially, HMTA self-assembles to fibrous structures and traps blank lubricant oils to form gel lubricants. The prepared gel lubricants show thermo-reversible properties and enhanced lubricating performance by 3∼5-fold. X-ray photoelectron spectrometry of the metal surface and the quartz crystal microbalance illustrated that there are no obvious interactions between HMTA and the metal surface. The results of Fourier transform infrared spectroscopy and X-ray diffraction further confirm that inter/intro-molecular H-bonding interactions are the main driving force for the self-healing of HMTA. Finally, molecular dynamics (MD) simulations show that the number of noncovalent H-bonding interactions fluctuates with time, and this highly dynamic H-bonding network could regulate the self-assembly process and result in the self-healing property of the HMTA organogel, which is consistent with the results of the step-strain tests. Especially, the Hirshfeld independent gradient model method at the quantum level demonstrated that C8/C9 aromatics of 500SN have strong π-π stacking interactions with the aromatic heads of HMTA and van der Waals interactions with the hydrophobic tails of HMTA, which disrupt the self-assembly behavior of the 500SN model. Therefore, the calculation studies offer a rational explanation for the superior lubricant property of the PAO10 gel as compared to that for 500SN.

Pd-Catalyzed γ-Acetoxylation of Alkylamides: Structural Influence of Directing Groups.

Although direct acetoxylation and cyclization of alkylamide have been extensively reported, investigation of the structural influence of directing groups on selectivity is limited. Pd-catalyzed 2-methoxyiminoacyl (MIA) assisted γ-acetoxylation of alkylamides has been developed. Further DFT studies have demonstrated that the directing groups have a significant influence on the reductive elimination step. The strong electron-donating effect of the OMe group in MIA leads to the preferential formation of a five-membered cyclopalladium (OAc-Pd-C) complex, which favors the acetoxylation pathway.

Pyromellitic-Based Low Molecular Weight Gelators and Computational Studies of Intermolecular Interactions: A Potential Additive for Lubricant.

Low molecular weight gelators (LMWG) have been extensively explored in many research fields due to their unique reversible gel-sol transformation. Intermolecular interactions between LMWG are known as the main driving force for self-assembly. During this self-assembly process, individually analyzing the contribution difference between various intermolecular interactions is crucial to understand the gel properties. Herein, we report 2,5-bis(hexadecylcarbamoyl)terephthalic acid (BHTA) as a LMWG, which could efficiently form a stable organogel with n-hexadecane, diesel, liquid paraffin, and base lubricant oil at a relatively low concentration. To investigate the contribution difference of intermolecular interactions, we first finished FT-IR spectroscopy and XRD experiments. On the basis of the d-spacing, a crude simulation model was built and then subjected to molecular dynamics (MD) simulations. Then, we knocked out the energy contribution of the H-bonding interactions and π-π stacking, respectively, to evaluate the intermolecular interactions significantly influencing the stability of the gel system. MD simulations results suggest that the self-assembly of the aggregates was mainly driven by dense H-bonding interactions between carbonyl acid and amide moieties of BHTA, which is consistent with FT-IR data. Moreover, wave function analysis at a quantum level suggested these electrostatic interactions located in the middle of the BHTA molecule were surrounded by strong dispersion attraction originating from a hydrophobic environment. Furthermore, we also confirmed that 2 wt % BHTA was able to form gel lubricant with 150BS. The coefficient of friction (COF) data show that the gel lubricant has a better tribological performance than 150BS base lubricant oil. Finally, XPS was performed and offered valuable information about the lubrication mechanism during the friction.

MIA-Directed 2-Pyridione-Enabled Selective Ortho-C-H Arylation of Phenylalanine: A Mechanistic Study.

The 2-methoxyiminoacyl-mediated arylation of substituted phenylalanines has been examined. Selective monoarylation at the ortho position was achieved using pyridone ligands which decelerate the arylation process. Density functional theory (DFT) study of a continuous C-H arylation process that included the first and second arylation stage was performed. The computational result shows that the introduction of a pyridone ligand obviously disfavors the second arylation stage, which directly contributes to the selectivity between the mono/diarylated products. Furthermore, results of the kinetic isotope effect and a control experiment are agreed with DFT study.

Synthetic Studies on Enantioselective Total Synthesis of Cyathane Diterpenoids: Cyrneines A and B, Glaucopine C, and (+)-Allocyathin B2.

The details for the synthetic studies on enantioselective total synthesis of cyathane diterpenoids cyrneine A (1) and B (2), glaucopine C (3), and (+)-allocyathin B2 are presented. We established a mild Suzuki coupling for heavily substituted nonactivated cyclopentenyl triflates using a phosphinamide-derived palladacycle as precatalyst and a chelation-controlled highly regioselective Friedel-Crafts cyclization. The utilization of these two key reactions enabled a rapid construction of the 5-6-6 tricyclic skeleton. In the middle stage of the synthesis, a Birch reductive methylation, a modified Wolff-Kishner-Huang reduction, and a carbenoid-mediated ring expansion were employed as the key reactions to furnish the 5-6-7 tricyclic core bearing two antiorientated all-carbon quaternary stereocenters at the C6 and C9 ring junctions. By applying these key transformations, a more efficient total synthesis of cyrneine A and allocyathin B2, and the first total synthesis of cyrneine B and glaucopine C, were accomplished through a collective manner. The late-stage conversions involving a base-mediated double bond migration and a double bond migration/aerobic γ-CH oxidation cascade for the stereoselective synthesis of cyrneine B and glaucopine C were interesting.

Tranylcypromine and 6-trifluoroethyl thienopyrimidine hybrid as LSD1 inhibitor.

Tranylcypromine moiety extracted from LSD1 inhibitors and 6-trifluoroethyl thienopyrimidine moiety from menin-MLL1 PPI inhibitors were merged to give new chemotypes for medicinal chemistry study. Among 15 new compounds prepared in this work, some exhibited nanomolar LSD1 activity and good selectivity over MAO-A/B, low micromolar menin-MLL1 PPI inhibitory activity, as well as submicromolar MV4-11 antiprofilative activities. Intracellular LSD1 engagement of compounds with higher enzymatic and antiproliferative activities was confirmed by CD86 mRNA up-regulation experiments.

Scaleable two-component gelator from phthalic acid derivatives and primary alkyl amines: acid-base interaction in the cooperative assembly.

A series of phthalic acid derivatives (P) with a carbon-chain tail was designed and synthesized as single-component gelators. A combination of the single-component gelator P and a non-gelling additive n-alkylamine A through acid-base interaction brought about a series of novel phase-selective two-component gelators PA. The gelation capabilities of P and PA, and the structural, morphological, thermo-dynamic and rheological properties of the corresponding gels were investigated. A molecular dynamics simulation showed that the H-bonding network in PA formed between the NH of A and the carbonyl oxygen of P altered the assembly process of gelator P. Crude PA could be synthesized through a one-step process without any purification and could selectively gel the oil phase without a typical heating-cooling process. Moreover, such a crude PA and its gelation process could be amplified to the kilogram scale with high efficiency, which offers a practical economically viable solution to marine oil-spill recovery.

Metal-Free Aerobic Oxidative Cyanation of Tertiary Amines: Azobis(isobutyronitrile) (AIBN) as a Sole Cyanide Source.

An aerobic oxidative cyanation for the synthesis of α-aminonitriles was reported. The formation of C(sp3)-CN bonds was achieved under a metal-free condition by utilizing azobis(isobutyronitrile) as a sole organic cyanide source with the combination of pivalic acid and sodium acetate as additives.

Boosting the catalysis of cesium phosphomolybdate encapsulated in hierarchical porous UiO-66 by microenvironment modulation for epoxidation of alkenes.

The chemical microenvironment of polyoxometalates (POMs) encapsulated in metal-organic frameworks (MOFs) presents a significant influence on their catalytic performance, which can be easily regulated by the linker functional group alteration or metal substitution in MOFs. Herein, a series of cesium phosphomolybdate (CsPM) encapsulated in hierarchical porous UiO-66-X composites (CsPM@HP-UiO-66-X, X = H, 2CH3, or 2OH, where X represents the alterable group grafted onto the linker benzene ring) were successfully synthesized through a one pot modulated solvothermal method. The catalytic performances of the obtained materials were explored in alkene epoxidation reaction with tert-butyl hydroperoxide (t-BuOOH). CsPM@HP-UiO-66-2CH3 showed relatively high catalytic activity, stability, and epoxidation selectivity in cyclooctene epoxidation among the CsPM@HP-UiO-66-X composites. Moreover, CsPM@HP-UiO-66-2CH3 was effective in the epoxidation of numerous alkenes, especially cyclic alkenes. The superior catalytic activity of CsPM@HP-UiO-66-2CH3 is mainly attributed to the modulation of the microenvironment surrounding CsPM active sites by introducing a hydrophobic methyl group. Meanwhile, the size-matched effect, the introduction of cesium cations, and the strong metal-support interactions (SMSIs) between CsPM and HP-UiO-66-2CH3 play a crucial role in the stability of CsPM@HP-UiO-66-2CH3.

Modulated synthesis of cesium phosphomolybdate encapsulated in hierarchical porous UiO-66 for catalysing alkene epoxidation.

The hybrid composite of cesium phosphomolybdate (CsPM) encapsulated in hierarchical porous UiO-66 (HP-UiO-66) was synthesized using a modulated solvothermal method. A variety of characterization results demonstrated that the pore size distribution of CsPM@HP-UiO-66 is broader than traditional microporous CsPM@UiO-66 and cesium phosphomolybdate clusters are uniformly distributed in the octahedral cages of HP-UiO-66. The catalytic properties of the hybrid composite were investigated in alkene epoxidation reaction with tert-butyl hydroperoxide (t-BuOOH) as an oxidant. CsPM@HP-UiO-66 showed much higher catalytic activity for the alkene epoxidation reaction in comparison with the reference catalysts and could be easily reused by centrifugation and recycled for at least ten runs without significant loss in catalytic activity. The superior catalytic activity and stability of the hybrid composite CsPM@HP-UiO-66 should be mainly attributed to the hierarchical pores in the support HP-UiO-66 promoting the diffusion of alkene molecules, the uniform distribution of highly active CsPM clusters in the octahedral cages of HP-UiO-66, the introduction of cesium cations to form the insoluble cesium phosphomolybdate and the strong metal-support interactions (SMSI) between the CsPM clusters and the HP-UiO-66 framework.

Metallophilic Interaction-Mediated Hierarchical Assembly and Temporal-Controlled Dynamic Chirality Inversion of Metal-Organic Supramolecular Polymers.

The study of dynamic supramolecular chirality inversion (SMCI) not only helps to deepen the understanding of chiral transfer and amplification in both living organizations and artificially chemical self-assembly systems but also is useful for the development of smart chiral nanomaterials. However, it is still challenging to achieve the dynamic SMCI of the self-aggregation of metal-organic supramolecular polymers with great potential in asymmetric synthesis, chiroptical switches, and circular polarized luminescence. Here, we successfully developed a hierarchical coassembly system based on the mPAzPCC and various metal ions with effective chirality transfer and temporal-controlled SMCI. Due to the dynamic self-assembly and hierarchical chirality transfer of the Ag+/mPAzPCC complex driven by metallophilic interaction and coordination, morphological transition with nanoribbons, helical nanoribbons, and chiral nanotubules was successively obtained. Interestingly, the SMCI of chiral nanoaggregates was precisely regulated by solvents and metal ions in the Cu2+/mPAzPCC and Mn2+/mPAzPCC system. Besides, temporal-controlled dynamic SMCI switching from helix to bundled helix was clearly revealed in the aggregation of Cu2+/mPAzPCC, Mn2+/mPAzPCC, and Bi3+/mPAzPCC systems. This work provides a metallophilic interaction-mediated helical assembly pathway to dynamically modulate the chirality of metal-organic complex-based assemblies and deepen the understanding of the hierarchically dynamic self-assembly process, which would be of great potential in metal ion-mediated supramolecular asymmetric catalysis and bioinspired chiral sensing.

Kinetic Resolution of 2,2-Disubstituted Dihydroquinolines through Chiral Phosphoric Acid-Catalyzed C6-Selective Asymmetric Halogenations.

A novel kinetic resolution of 2,2-disubstituted dihydroquinolines was achieved by regioselective asymmetric halogenations enabled by chiral phosphoric acid catalysis. A series of dihydroquinolines bearing 2,2-disubstitutions were well-tolerated in these reactions, generating both the recovered dihydroquinolines and C-6-brominated products with high enantioselectivities, with s-factors up to 149. In addition, this kinetic resolution protocol is also applicable for 2,2-disubstituted tetrahydroquinoline and asymmetric iodonation reaction.

Au(I)-Catalyzed Domino Cyclization of 1,6-Diynes Incorporated with Indole.

We disclose herein a Au(I)-catalyzed domino cyclization of 1,6-diynes incorporated with indole. This protocol enabled the diastereoselective buildup of indole-fused azabicyclo[3.3.1]nonanes from linear precursors. Density functional theory calculations showed that the reaction proceeded via an unprecedented cascade dearomatization/rearomatization/dearomatization process. Independent gradient model analysis revealed that a noncovalent attractive interaction between the distal alkyne and the Au/proximal complex was responsible for the chemoselectivity of the first spirocyclization step.

Geometry transformation of ionic surfactants and adsorption behavior on water/n-decane-interface: calculation by molecular dynamics simulation and DFT study.

Understanding the effect of surfactant structure on their ability to modify interfacial properties is of great scientific and industrial interest. In this work, we have synthesized four amide based ionic surfactants under acidic or basic conditions, including CTHA·HCl, CTEA·HCl, CTHA-Na+ and CTEA-Na+. Experiments have proved that the anionic surfactant with polyethylene oxide groups (CTEA-Na+) had the lowest surface tension on the water/n-decane interface. Molecular dynamics simulations have been applied to investigate the structural effect on the adsorption behavior of four different surfactants. The surface tension, interface thickness, interface formation energy, density profiles, order parameters, radial distribution function on the water/n-decane interfaces were calculated and compared. During the equilibrium states, we found that the interface configuration of two cationic surfactants are almost linear while the two anionic surfactants are changed to bending shapes due to the different positions of the hydrophilic head groups. Further DFT study and wavefunction analysis of surfactants have shown that CTEA-Na+ can form stronger vdW interactions with n-decane molecules due to a more neutral electrostatic potential distribution. Meanwhile, the introduction of polyethylene oxide groups has offered more H-bonding sites and resulted in more concentrated H-bonding interactions with water molecules. The difference of weak interactions may contribute to the conformational change and finally affect the interface properties of these ionic surfactants.

Asymmetric Aza-Diels-Alder Reactions of in Situ Generated ß,ß-Disubstituted α,ß-Unsaturated N-H Ketimines Catalyzed by Chiral Phosphoric Acids.

A novel asymmetric synthesis of dihydropyridinones with vicinal quaternary stereocenters has been realized by asymmetric aza-Diels-Alder reactions of 3-amido allylic alcohols with oxazolones enabled by chiral phosphoric acid catalysis. A series of aryl/alkyl- and alkyl/alkyl-disubstituted 3-amido allylic tertiary alcohols and 4-substituted oxazolones could be well tolerated in these reactions, producing dihydropyridinones with excellent diastereoselectivities and high enantioselectivities. Mechanistic study and control experiments were performed to shed light on the reaction mechanism, in which a configurationally defined ß,ß-disubstituted α,ß-unsaturated N-H ketimine was proposed as the key intermediate.

Visible-light driven synthesis of polycyclic benzo[d][1,3]oxazocine from 2-aminochalcone.

Herein, we report a tandem cycloisomerization/nucleophilic addition/cyclization of 2-amino chalcone with bifunctional nucleophiles driven by visible light. This cascade process is realized by the irradiation of a blue LED at room temperature, which provides a concise route to structurally diverse benzo[d][1,3]oxazocine scaffolds. Mechanistic studies show that the reaction is initiated with the E to Z isomerization of a C-C double bond upon the irradiation of visible light, followed by cyclization/rearomatization to generate a transient quinolinium intermediate, which is trapped by the nucleophile and cyclized to produce the polycyclic benzo[d][1,3]oxazocine.

Biosynthetic Hypothesis-Guided Discovery and Total Syntheses of PKS-NRPS Hybrid Metabolites from Endophytic Fungus Periconia Species.

Guided by our biosynthetic hypothesis, pericoannosins C-F, four new PKS-NRPS hybrid metabolites, were discovered from the endophytic fungus Periconia sp. F-31. Their structures and absolute configurations were elucidated by extensive spectroscopic data and electronic circular dichroism analyses. Preliminary biological evaluation revealed that pericoannosins C-D exhibited anti-HIV activities with IC50 values of 15.5 and 13.5 µM. Furthermore, the bioinspired syntheses of pericoannosins C-E have also been completed with high efficiency.

Flexible total synthesis of biphenomycin B.

A total synthesis of the biaryl antibiotic biphenomycin B is reported which makes use of three independent building blocks (key steps were a clean Suzuki-Miyaura coupling of a free acid iodide, a novel 4-hydroxyornithine synthesis, and a high-yielding macrolactamization); a practical deprotection protocol allowed isolation of the target compound with excellent recovery and purity.

Catalytic, metal-free sulfonylcyanation of alkenes via visible light organophotoredox catalysis.

The group transfer radical addition of olefins with tosyl cyanide has been accomplished via visible light-induced organophotoredox catalysis. A diverse array of olefins is amenable to this protocol, furnishing ß-sulfonyl nitriles with excellent efficiency under metal-free and redox-neutral conditions. A closed catalytic cycle is operative in this transformation, providing complementary reactivity to the classic radical chain process.