Functional Group Transformations Research Articles

Photoinduced Tandem Cyanomethylation/Cyclization of Unsaturated Compounds: Access to Cyanomethylated 7- or 5-Membered N-Heterocycles.

A cyanomethylation/cyclization of aryl acetylenes/ethylenes with bromoacetonitrile was finished in a photopromoted condition, which offers an efficient and mild protocol for the preparation of cyanomethylated 7- or 5-membered N-heterocycles with good yields. Meanwhile, trichloroacetonitrile was also compatible with this radical pathway. In addition, a variety of single-crystal X-ray diffraction measurements, scaled-up operations to 1 mmol, functional group transformations of final products, light on/off experiments, and even radial inhibition studies were smoothly performed in this tandem system.

Multigram Synthesis of α‐ and γ‐((Hetera)cyclo)alkylpyridines through α‐Arylation of (Hetero)aliphatic Nitriles

AbstractA systematic study on the SnAr reaction of halogenated fluoropyridines and (hetero)aliphatic nitrile anions as an approach to the synthesis of functionalized pyridines bearing a (cyclo)alkyl or saturated heterocyclic substituent by is described. The scope of the method was demonstrated on a wide range of (hetero)aliphatic nitriles (including three‐ to six‐membered cycloalkane derivatives and N‐, O‐, S‐containing saturated heterocycles) and all isomeric halogenated 2‐and 4‐fluoropyridines. High chemo‐ and regioselectivity (i. e., exclusive substitution of the fluorine atom), as well as excellent scalability of the proposed reaction sequence were demonstrated (up to 450 g for the arylation step or up to 77 g of cycloalkylpyridine over two steps in a single run). The utility of the synthesized products was illustrated in the additional functional group transformations resulting in synthetically valuable pyridine‐containing building blocks.

Nickelacarborane-Supported Bis-N-heterocyclic Carbenes.

Metallacarboranes have attracted significant attention due to their unique properties. Considerable efforts have been made on the reactions around the metal centers or the metal ion itself, while transformations of functional groups of the metallacarboranes have been much less explored. We presented here the formation of imidazolium-functionalized nickelacarboranes (2), their subsequent conversion to nickelacarborane-supported N-heterocyclic carbenoids (NHCs, 3), and the reactivities of 3 toward Au(PPh3)Cl and Se powder, which resulted in the formation of bis-gold carbene complexes (4) and NHC selenium adducts (5). Cyclic voltammetry of 4 shows two reversible peaks, corresponding to the interconversion transformations NiII ↔ NiIII and NiIII ↔ NiIV. Theoretical calculations demonstrated relatively high-lying lone-pair orbitals, weak B-H···H-C interactions between the BH units and the methyl group, and weak B-H···π interactions between the BH groups and the vacant p-orbital of the carbene.

Preparation and inhibition performance of dry water materials for preventing spontaneous combustion of coal

This work aimed to effectively prevent the spontaneous combustion of coal in goafs by preparing a type of dry water material with a solid-in-liquid structure through the mechanical stirring method, with nano-aluminum hydroxide aqueous solution as the core material and hydrophobic nano-silicon dioxide as the wall material. The effects of solid-to-liquid ratio, stirring time, and mass concentration of nano-aluminum hydroxide on the particle size and microstructure of dry water were studied. Results showed that the prepared dry water powder was the most uniform and fine when nano-silica, nano-aluminum hydroxide, and water were mixed at a mass ratio of 5:0.75:49.25 and stirred at a speed of 23,000 r/min for 25 s. The samples were characterized by using a temperature-programmed oxidation device, a thermogravimetric analyzer, and a Fourier-transform infrared spectrometer, and the inhibition performance of dry water was evaluated. Results revealed that dry water effectively slowed the oxidation rate of coal and inhibited the release of CO in the low-temperature environment, and the cross-point temperature increased from 125.1 °C to 155.4 °C for raw coal. In a high-temperature environment, dry water delayed the process of spontaneous combustion of coal, the temperature leading to the maximum mass increased from 308.6 °C to 369.4 °C, and the ignition temperature rose from 458.2 °C to 484.7 °C. In addition, the dry water material can inhibit the oxidative decomposition of aliphatic hydrocarbons and the transformation of oxygen-containing functional groups in coal samples, thus indicating, from a microscopic level, that it has good inhibition performance.

Ru(II)-Catalyzed Weakly Coordinating Carbonyl-Assisted Dialkynylation of (Hetero)Aryl Ketones.

Functionalized aryl(heteroaryl) ketones are present in many natural products as key structural components and serve as basic synthetic building blocks for various organic transformation reactions. Therefore, the development of an effective and sustainable route for making these classes of compounds remains challenging yet highly desirable. Herein, we report a simple and efficient catalytic system for dialkynylation of aromatic/heteroaromatic ketones via a double C-H bond activation in the presence of less expensive ruthenium(II)-salt as a catalyst using the weakly and native carbonyl group as the desired directing group. The developed protocol is highly compatible, tolerant, and sustainable toward various functional groups. The synthetic utility of the developed protocol has been demonstrated through the scale-up synthesis and functional group transformation. Control experiments support the involvement of the base-assisted internal electrophilic substitution (BIES) reaction pathway.

Recent Advances in the Gold-Catalyzed Reactions of Propargyl Esters.

ConspectusLate-transition-metal-based complexes represent an indispensable catalytic tool in chemical synthesis due to their ability to increase molecular complexity rapidly and efficiently from readily accessible substrates in a single operation. Added to this is the exquisite control of product chemo-, diastereo-, enantio-, and site-selectivities achieved by catalytic systems of the transition-metal salts that have been developed to mediate a wide range of functional group transformations. Within this venerable synthetic toolbox, complexes and salts of Au(I) and Au(III) have emerged in recent years as an invaluable addition as a result of their potent σ- and π-Lewis acidities and ability to stabilize cationic reaction intermediates. The insights provided by mechanistic studies examining the various electronic, steric, and stereoelectronic factors at play in the organogold species that are expected to be formed in the catalytic chemistry of the transition-metal complex have also been pivotal in understanding and exploring their potential synthetic utility. Illustrative of this, for example, is the contribution made by the gold-catalyzed cycloisomerization chemistry of propargyl esters in synthetic strategies to a variety of bioactive natural products and compounds of current pharmaceutical and materials interest. This Account summarizes our efforts over the past decade toward realizing new single-step strategies for carbocyclic and heterocyclic synthesis that relied on the gold-catalyzed reactions of propargyl esters. It outlines synthetic methods developed by the group that exploited the unique reactivities of the gold-carbene species typically generated from the [2,3]-sigmatropic rearrangement of the compound class containing a terminal or electron-deficient alkyne moiety on exposure to the transition-metal salt. This Account also describes the realization of synthetic methods initiated by the gold-catalyzed 1,3-acyloxy migration of propargyl esters with an electronically unbiased disubstituted C≡C bond that delivers the corresponding allenyl ester that is primed for further reactivity on activation by the group 11 metal complex. The studies formed a part of an ongoing overarching program within our group that was focused on determining reactivities in gold catalysis that would enable their application as readily recognizable disconnections in retrosynthetic analysis. They were additionally a part of efforts aimed at evaluating the opportunities offered by the relativistic effects possessed by a Au(I) and Au(III) complex, the most pronounced among the d-block elements and thus the catalyst of choice in alkyne activation chemistry, to generate new chemical space. For instance, we demonstrated in several studies the cycloisomerization of 1,3- and 1,4-enyne esters to be a reliable strategy for the in situ formation of a wide range of 1,4-cyclopentadienyl derivatives. Their further reaction with an appropriately placed functional group or a second starting material was then shown to afford a variety of synthetic targets containing the five-membered ring structure. An example of this was the assembly of a new member of the 1H-isoindole compound family that was found to exhibit potent TNF-α (tumor necrosis factor-α) inhibitor activity.

Detection of Nitroaromatic and Peroxide-Based Explosives with Amine- and Phosphine-Functionalized Diketopyrrolopyrroles.

Effective strategies for the detection and identification of explosives are highly desirable. Herein, we illustrate the efficient optoelectronic detection of nitroaromatic and peroxide-based explosives using amine- and phosphine-substituted diketopyrrolopyrroles. Selective quenching and an unprecedented enhancement of thin-film emission in the presence of nitroaromatic vapors are demonstrated via the judicious choice of amine substituents. The modulation of fluorescence emission in each case is shown to be dominated by electronic and thermodynamic effects, the vapor pressure of explosives, and the thin-film morphology. For peroxide detection, we describe an approach exploiting redox-mediated functional group transformation. The rapid oxidation of triphenylphosphine to phosphine oxide with hydrogen peroxide affords a significant increase in fluorescence emission, facilitating the sensitive turn-on detection of an important class of explosives at ppb concentrations.

Direct Synthesis of Aliphatic Polyesters with Pendant Hydroxyl Groups from Bio-Renewable Monomers: A Reactive Precursor for Functionalized Biomaterials.

Introducing desired functionalities into biomaterials is an effective way to obtain functionalized biomaterials. A versatile platform with the possibility of postsynthesis functionalization is highly desired but challenging in biomedical engineering. In this work, linear aliphatic polyesters with pendant hydroxyl (PEOH) groups were directly synthesized using renewable malic acid/tartaric acid as raw materials under mild conditions through the polyesterification reaction promoted by 1,1,3,3-tetramethylguanidine (TMG). The hydroxyl groups on PEOH provide an active stepping stone for the fabrication of demanded functionalized polyesters. We demonstrated the possibility of the PEOH as a reactive precursor for functional group transformation, coupling of bioactive molecules, and formation of crosslinking networks. Moreover, a theranostic nanoplatform (mPEG-b-(P7-asp&TPV)-b-mPEG NPs) was synthesized using PEOH as a reactive stepping stone by the programmable combination of the above functionalization methods. Overall, these hydroxyl-containing polyesters have great potential in biological applications.

Efficient Transformation of Polymer Main Chain Catalyzed by Macrocycle Metal Complexes via Pseudorotaxane Intermediate

AbstractPost‐synthesis modification of polymers streamlines the synthesis of functionalized polymers, but is often incomplete due to the negative polymer effects. Developing efficient polymer reactions in artificial systems thus represents a long‐standing objective in the fields of polymer and material science. Here, we show unprecedented macrocycle‐metal‐complex‐catalyzed systems for efficient polymer reaction that result in 100 % transformation of the main chain functional groups presumably via a processive mode reaction. The complete polymer reactions were confirmed in not only intramolecular reaction (hydroamination) but also intermolecular reaction (hydrosilylation) by using Pd‐ and Pt‐macrocycle‐catalyzed systems. The most fascinating feature of the both reactions is that higher‐molecular‐weight polymers reach completion faster. Various studies suggested that the reactions occur in the catalyst cavity via the formation of a supramolecular complex between the macrocycle catalyst and polymer substrate like pseudorotaxane, which should be of characteristic of the efficient polymer reactions progressing in a processive mode.

Efficient Transformation of Polymer Main Chain Catalyzed by Macrocycle Metal Complexes via Pseudorotaxane Intermediate.

Post-synthesis modification of polymers streamlines the synthesis of functionalized polymers, but is often incomplete due to the negative polymer effects. Developing efficient polymer reactions in artificial systems thus represents a long-standing objective in the fields of polymer and material science. Here, we show unprecedented macrocycle-metal-complex-catalyzed systems for efficient polymer reaction that result in 100 % transformation of the main chain functional groups presumably via a processive mode reaction. The complete polymer reactions were confirmed in not only intramolecular reaction (hydroamination) but also intermolecular reaction (hydrosilylation) by using Pd- and Pt-macrocycle-catalyzed systems. The most fascinating feature of the both reactions is that higher-molecular-weight polymers reach completion faster. Various studies suggested that the reactions occur in the catalyst cavity via the formation of a supramolecular complex between the macrocycle catalyst and polymer substrate like pseudorotaxane, which should be of characteristic of the efficient polymer reactions progressing in a processive mode.

Diverse Synthetic Transformations Using 4-Bromo-3,3,4,4-tetrafluorobut-1-ene and Its Applications in the Preparation of CF2 CF2 -Containing Sugars, Liquid Crystals, and Light-Emitting Materials.

Organic molecules with fluoroalkylene scaffolds, especially a tetrafluoroethylene (CF2 CF2 ) moiety, in their molecular structures exhibit unique biological activities, or can be applied to functional materials such as liquid crystals and light-emitting materials. Although several methods for the syntheses of CF2 CF2 -containing organic molecules have been reported to date, they have been limited to methods using explosives and fluorinating agents. Therefore, there is an urgent need to develop simple and efficient approaches to synthesize CF2 CF2 -containing organic molecules from readily available fluorinated substrates using carbon-carbon bond formation reactions. This personal account summarizes the simple and efficient transformation of functional groups at both ends of 4-bromo-3,3,4,4-tetrafluorobut-1-ene and discusses its synthetic applications to biologically active fluorinated sugars and functional materials, such as liquid crystals and light-emitting molecules.

Total Synthesis of Campylobacter jejuni NCTC11168 Capsular Polysaccharide via the Intramolecular Anomeric Protection Strategy

The infection of Campylobacter jejuni results in a significant diarrhea disease, which is highly fatal to young children in unindustrialized countries. Developing a new therapy is required due to increasing antibiotic resistance. Herein, we described a total synthesis of a C. jejuni NCTC11168 capsular polysaccharide repeating unit containing a linker moiety via an intramolecular anomeric protection (iMAP) strategy. This one-step 1,6-protecting method structured the challenging furanosyl galactosamine configuration, facilitated further concise regioselective protection, and smoothed the heptose synthesis. The tetrasaccharide was constructed in a [2 + 1 + 1] manner. The synthesis of this complicated CPS tetrasaccharide was completed in merely 28 steps, including the preparation of all the building blocks, construction of the tetrasaccharide skeleton, and functional group transformations.

Modular Click Assembly DNA-Encoded Glycoconjugate Libraries with on-DNA Functional Group Transformations.

Carbohydrates are an important class of naturally active products and play vital roles in regulating various physiological activities. To meet the demand for carbohydrate-based libraries used for the identification of potential drug candidates for pharmaceutical-related targets, we developed a set of on-DNA protocols to construct the DNA-encoded glycoconjugates, including Seyferth-Gilbert homologation, anomeric azidation, and CuAAC cyclization. These on-DNA chemistries enable the generation and modification of DNA-linked glycosyl compounds with good conversions and broad substrate scope. Finally, three DNA-linked glycoconjugate libraries were successfully generated to demonstrate their applicability and feasibility in library preparation.

An Intramolecular Umpolung Cascade Kukhtin-Ramirez Reaction/Michael Addition-Initiated Cyclization: Stereoselective Synthesis of Tetrasubstituted Cyclopropane Fused 1-Indanones.

Herein, we disclose a fascinating highly stereoselective P(NMe2)3 mediated intramolecular deoxygenative umpolung cascade Michael addition-initiated cyclopropanation with a diverse substrate adaptability. This methodology creates a new horizon for expedient access to valuable 6,5,3-fused scaffolds having an all-carbon quaternary stereocenter via Kukhtin-Ramirez (K-R) adduct formation, with excellent diastereoselectivity and yields under metal-free ambient conditions. A few functional group transformations have also been performed successfully. Additionally, an asymmetric catalytic attempt using (R)-(+)-H8-BINOL has delivered good enantioselectivity.

Solid‐Supported Catalysts for Organic Functional Group Transformations

AbstractDesign of solid‐supported metal catalysts (SSMCs) has made an increasingly important contribution to heterogeneous catalysis in terms of fundamental understanding and technological applications. For instance, industrial use of supported catalysts for oxidation, reduction, and C−C bond formation reactions is highly prevalent. The reason behind this is that such catalysts are economical, have high thermal stability, dispersion, high exposed surface area, and above all, high reusability (up to multiple subsequent cycles). Such characteristics make supported catalysts ideal for green synthesis. However, unlike homogeneous catalysis, heterogeneous catalysis is widely applied in crude oil refining, the pharmaceutical industry, water purification, natural product synthesis, and environmental catalysis. Carbon‐carbon bond formation reactions are frequently used in the organic synthesis using SSMCs. SSMCs are attractive to synthetic chemists due to their easy recovery and excellent stability compared to unsupported metal catalysts. However, the major drawback of SSMCs is related to metal sintering at elevated temperatures caused by weak interactions between the metal and solid support in SSMCs. This review highlights major advancements in SSMCs. Three commonly reported solid supports for metal catalysts, such metal oxides, carbonaceous materials, and polymeric compounds, are discussed. Moreover, a series of thermo‐ and photocatalyzed reactions, such as hydrogenation, carbon‐carbon bond formation, oxidation reactions and multicomponent reactions and the effect of variable supports towards activity and selectivity are demonstrated.

A Mild Method for the Replacement of a Hydroxyl Group by Halogen: 4. Practical Synthesis of Cyclic β-Halovinylketones under Neutral Conditions

AbstractThe replacement of a hydroxyl group by a halogen is a pivotal organic functional group transformation. Existing procedures often require acidic conditions or lack sustainability and atom economy. We have previously shown that tetramethyl-α-haloenamines (TMXE) or 2,2-dimethyl-1-halo-1-diisopropylamines (DIXE) react with a wide variety of hydroxyl-containing molecules to yield the corresponding halides under very mild conditions and with high atom economy. We now show that the deoxyhalogenation reactions of the enol tautomers of cyclic1,3-diketones and of 2-hydroxymethylene cycloketones can also be performed with TMCE or DIXE to yield β-halo-α,β-unsaturated ketones in excellent yields. The reactions are regioselective and in some cases stereoselective. The reaction is also successful with acetylacetone but the yield is only moderate. β-Ketoesters are not reactive. The method favorably compares to the best existing methods: It is more general, occurs under very mild conditions, which should allow acid-sensitive functional groups such as ketals, esters, ethers, etc., to be tolerated, and, above all, is quite sustainable (no toxic reagents or products).

An Amino Acid‐Based Thixotropic Hydrogel: Tuning of Gel Recovery Time by Mechanical Shaking

AbstractFmoc‐Trp‐OH (Fmoc: N‐fluorenylmethoxycarbonyl; Trp‐OH: L‐Tryptophan) undergone hydrogelation at 50 mM phosphate buffer saline of pH 7.4 with a minimum gelation concentration (MGC) of 0.25 % w/v after 12 to 15 hours. However, the hydrogel formation kinetics can be faster just by mechanical hand shaking of the hydrogelator solution during the hydrogel preparation procedure. The shake hydrogel is thermally and mechanically more stable than the non‐shake hydrogel. These hydrogels have been characterized thoroughly by Tgel estimations, UV‐Vis spectroscopy, Fluorescence spectroscopy, Fourier Transform‐Infra Red (FT‐IR) Spectroscopy, X‐ray diffractions (XRD), Field Emission Scanning Electron Microscopy (FE‐SEM) and rheology. This amino acid‐based hydrogel is thixotropic in nature and interestingly without doping any foreign materials into the hydrogel, the gel reformation kinetics can be faster just by number of times breaking of the hydrogel by mechanical hand shaking followed by keeping the hydrogel glass vial at rest. This holds future promise to develop supramolecular mechanocatalyst for various functional group transformation reactions in water through green and sustainable chemistry pathways.

Temperature-Controlled Divergent Asymmetric Synthesis of Indole-Based Medium-Sized Heterocycles through Palladium Catalysis

The divergent construction of chiral medium-sized rings is an essential but challenging task in organic synthesis. Herein, we report a temperature-controlled catalytic system for the divergent, enantioselective synthesis of different types of medium-sized rings starting from the same substrate set. Enabled by a planar chiral bisphosphine ligand, the palladium-catalyzed (5 + 4) and formal (5 + 2) annulations of cyclic aza-dienes and vinylethylene carbonates proceeded smoothly to afford a broad spectrum of indole-based medium-sized heterocycles in excellent yields with outstanding enantioselectivities. Those products could be further diversified through various functional group transformations. Moreover, mechanistic studies, including control experiments and DFT calculations, shed light on understanding the observed regio- and enantioselectivities of palladium-catalyzed (5 + n) cyclization.

Hydrolysis, Microstructural Profiling and Utilization of Cyamopsis tetragonoloba in Yoghurt

The present study investigates the hydrolysis, microstructural profiling and utilization of guar gum (Cyamopsis tetragonoloba) as a prebiotic in a yoghurt. Guar galactomannans (GG) was purified and partially depolymerized using an acid, alkali and enzyme to improve its characteristics and increase its utilization. The prebiotic potential of hydrolyzed guar gum was determined using Basel and supplemented media. Crude guar galactomannans (CGG), purified guar galactomannans (PGG), base hydrolyzed guar galactomannans (BHGG), acid hydrolyzed guar galactomannans (AHGG) and enzymatic hydrolyzed guar galactomannans (EHGG) were analyzed using scanning electron microscope (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Yoghurt was prepared with a starter culture and incorporating guar gum, its hydrolyzed forms (0.1, 0.5 and 1%) and Bifidobacterium bifidum. The results showed that PHGG significantly improved the viability of B. bifidum. SEM revealed a significant change in the surface morphology of guar gum after acidic and enzymatic hydrolysis. Enzymatic hydrolysis developed a well-defined framework within guar gum molecules. The XRD pattern of CGG, PGG and AHGG presented an amorphous structure and showed low overall crystallinity while EHGG and BHGG resulted in slightly increased crystallinity regions. FTIR spectral analysis suggested that, after hydrolysis, there was no major transformation of functional groups. The addition of the probiotic and prebiotic significantly improved the physiochemical properties of the developed yoghurt. The firmness, cohesiveness, adhesiveness and syneresis were increased while consistency and viscosity were decreased during storage. In sum, a partial hydrolysis of guar gum could be achieved using inexpensive methods with commercial significance.

Reaction-based energy level modulation of a cyclometalated iridium complex for electrochemiluminescent detection of formaldehyde.

Formaldehyde is a toxic compound present in both the environment and living systems, and its detection is important due to its association with various pathological process. In this study, we report a new electrochemiluminescence (ECL) probe based on a cyclometalated iridium complex (IrHAA) for the selective detection of formaldehyde. The homoallylamine moiety in IrHAA reacts with formaldehyde, undergoing a 2-aza-Cope-rearrangement reaction to form a formyl group. Significant changes in the electronic properties and molecular orbital energies of the iridium complex through the functional group transformation result in enhanced ECL and radiometric phosphorescence changes, enabling the quantitative and selective detection of formaldehyde. The energetic requirements for ECL sensing were investigated, highlighting the importance of the excited state energy for achieving efficient ECL. The sensing mechanism was elucidated using NMR spectroscopy and MALDI-TOF analysis.