Simple Functional Group Research Articles

Copper-Initiated Regiodivergent Chloropentafluorosulfanylation of 1,3-Enynes under Substrate Control.

A copper-catalyzed regiodivergent chloropentafluorosulfanylation strategy for 1,3-enynes using SF5Cl has been developed. The regioselectivity is dictated by the structural and substitution patterns of 1,3-enynes, enabling facile access to three classes of SF5-containing products: propargylic chlorides, 1,3-dienes, and allenes. The reaction systems involve radical species, where the transfer of a chlorine atom from SF5Cl to a carbon radical is considered the predominant pathway. Diverse types of SF5- building blocks can be synthesized through simple functional group transformations.

Cooperative Cu/azodiformate system-catalyzed allylic C–H amination of unactivated internal alkenes directed by aminoquinoline

Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp3)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp3)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.

Ligand Relay for Nickel-Catalyzed Decarbonylative Alkylation of Aroyl Chlorides.

Transition metal-catalyzed direct decarboxylative transformations of aromatic carboxylic acids usually require high temperatures, which limit the substrate's scope, especially for late-stage applications. The development of the selective decarbonylative of carboxylic acid derivatives, especially the most fundamental aroyl chlorides, with stable and cheap electrophiles under mild conditions is highly desirable and meaningful, but remains challenging. Herein, a strategy of nickel-catalyzed decarbonylative alkylation of aroyl chlorides via phosphine/nitrogen ligand relay is reported. The simple phosphine ligand is found essential for the decarbonylation step, while the nitrogen ligand promotes the cross-electrophile coupling. Such a ligand relay system can effectively and orderly carry out the catalytic process at room temperature, utilizing easily available aroyl chlorides as an aryl electrophile for reductive alkylation. This discovery provides a new strategy for direct decarbonylative coupling, features operationally simple, mild conditions, and excellent functional group tolerance. The mild approach is applied to the late-stage methylation of various pharmaceuticals. Extensive experiments are carried out to provide insights into the reaction pathway and support the ligand relay process.

Copper‐Catalyzed Olefinic C(sp2)−H Activation/Carbene Insertion/Ester Hydrolysis/Cyclization with Aryl Diazo Esters for the Synthesis of Multisubstituted Furanones

AbstractA copper‐catalyzed olefinic C(sp2)−H activation/carbene insertion/ester hydrolysis/cyclization sequence has been developed for the synthesis of substituted 2(5H)‐furanones employing readily available enaminones and aryl diazo esters as substrates. This method features operationally simple and good functional group tolerance. The transformation could be scaled up to gram quantities and the obtained 2(5H)‐furanone derivatives could be easily converted to a wide range of useful synthetic building blocks, indicative of the applicability of the synthetic strategy. Isotope labeling experiments demonstrated the ester group of diazo esters was hydrolyzed during the reaction.

Highly dispersed Cu2O quantum dots (about 2 nm) constructed by a simple functional group anchoring strategy boost the photocatalytic water splitting ability by 72 times

Ultra-small Cu2O QDs with an average particle size of only 1.8 nm were anchored on the TiO2 surface. The QDs are uniformly dispersed and the photocatalytic hydrogen evolution yield is 72 times higher than that of commercial P25.

Joining of metal and non-polar polypropylene composite through a simple functional group seeding layer

Polypropylene (PP) and its composites are one of the hardest to directly join with metals due to their inherent chemical incompatibility. This paper presents a simple, efficient, and cost-effective method for joining PP composite to aluminum alloy in spot welding configuration by seeding the functional groups via an insert layer of PA6 thin film without requiring surface or material pre-treatment. The resulting joint loading capacity is shown to be sufficiently high to consistently develop failures in PP substrates in lap shear tensile tests away from the bonded area. Joint interface microstructure features are examined in detail. Bonding mechanisms are then described based on the detailed observations obtained in this study.

A Simple Mechanochromic Mechanophore Based on Aminothiomaleimide.

Mechanochromic mechanophores have promising applications in stress sensing and damage detection. Here we report a simple mechanofluorochromic mechanophore based on aminothiomaleimide (ATM). Poly(methyl acrylate) containing this mechanophore (ATM-PMA) was synthesized by atom transfer radical polymerization (ATRP) using an ATM-derived difunctional initiator. To investigate its mechanofluorochromism, the solution of ATM-PMA was subjected to ultrasonication, and size exclusion chromatography (SEC) and fluorescence spectroscopy were employed to monitor the changes in molecular weight and fluorescence emission. The results showed that the molecular weight of ATM-PMA decreased upon ultrasonication, accompanied by a shift of fluorescence emission from bright yellow to light blue. This mechanophore of a simple functional group of ATM has great potential to be used in mechanochromic polymer materials.

Asymmetric Synthesis of Lysergic Acid via an Intramolecular (3+2) Dipolar Cycloaddition/Ring-Expansion Sequence.

An effective, potentially scalable asymmetric synthesis of lysergic acid, a core component of the ergot alkaloid family, is reported. The synthesis features the strategic combination of an intramolecular azomethine ylide cycloaddition and Cossy-Charette ring expansion to assemble the target's C- and D-rings. Simple functional group manipulation produced a compound that had been converted to lysergic acid in four steps, thus constituting a formal synthesis of the natural product. The strategy may be used to prepare novel ergot analogues that include unnatural antipodes and may be more amenable to analogue generation relative to prior approaches.

Enantioselective Self-Assembled Nanofibrillar Network with Glutamide-Based Organogelator.

A chiral molecular gelation system, as a chiral host, was used to effectively realize enantioselectivity using the simple carboxylic acid functional group. For this purpose, an L-glutamic-acid-based lipidic amphiphile (G-CA) with a carboxylic head group was selected and its responsiveness to cationic guest molecules was investigated. The dispersion morphology of G-CA in its solution state was examined by confocal and transmission electron microscopies, while interactions between the G-CA, as the host system, and guest molecules were evaluated by UV-visible, circular dichroism, and fluorescence spectroscopies. As a result, enantioselectivity was effectively induced when G-CA formed highly ordered aggregates that provide negatively charged surfaces in which carboxyl groups are assembled in highly ordered states, and when the two cationic groups of the guest molecule are attached to this surface through multiple interactions.

Macromolecular Design of Lithium Conductive Polymer as Electrolyte for Solid-State Lithium Batteries.

In the development of solid-state lithium batteries, solid polymer electrolyte (SPE) has drawn extensive concerns for its thermal and chemical stability, low density, and good processability. Especially SPE efficiently suppresses the formation of lithium dendrite and promotes battery safety. However, most of SPE is derived from the matrix with simple functional group, which suffers from low ionic conductivity, reduced mechanical properties after conductivity modification, bad electrochemical stability, and low lithium-ion transference number. Appling macromolecular design with multiple functional groups to polymer matrix is accepted as a strategy to solve the problems of SPE fundamentally. In this review, macromolecular design based on lithium conducting groups is summarized including copolymerization, network construction, and grafting. Meanwhile, the construction of single-ion conductor polymer is also focused herein. Moreover, synergistic effects between the designed matrix, lithium salt, and fillers are reviewed with the objective to further improve the performance of SPE. At last, future studies on macromolecular design are proposed in the development of SPE for solid-state batteries with high energy density and durability.

Combination of least absolute shrinkage and selection operator with Bayesian Regularization artificial neural network (LASSO-BR-ANN) for QSAR studies using functional group and molecular docking mixed descriptors

A combination of least absolute shrinkage and selection operator (LASSO) with Bayesian Regularization feed-forward artificial neural network (LASSO-BR-ANN) was used as a new approach in the quantitative structure-activity relationship (QSAR) studies. A mixture of the docking derived descriptors with the simple functional group (structural) features was also introduced as a new ensemble of descriptors for accurate QSAR modeling. The performance of introduced approaches was tested with QSAR modeling of the biological activities (pEC50) of 73 azine derivatives as new non-nucleoside reverse transcriptase inhibitors (NNRTIs) for treatment of HIV disease. Molecular docking descriptors (MDDs) were generated from ligand-receptor interactions and functional group features derived using Dragon 5.5 software. The dataset was divided into three sets of training, validation, and test data. LASSO, as a penalized regression method, was applied to the training data set for the selection of the most relevant descriptors among the mixture of the structural and MDDs. LASSO selected descriptors were used as inputs in the construction of the Bayesian Regularization artificial neural network (BR-ANN) model. The results showed that the addition of functional group properties to the MDDs improves the accuracy of the model. Under the optimum conditions, LASSO-BR-ANN was successfully applied for the prediction of PEC50 values for compounds in the external test set with mean square error (MSE) and coefficient of determination (R2) values of 0.07 and 0.88, respectively. Some of the prediction statistical parameters of the model were calculated and all of them were in their acceptable ranges, which confirm the validity of the proposed QSAR model.

Rhodium(III)‐Catalyzed Alkynylation of 4‐Arylphthalazin‐1(2H)‐one Scaffolds via C‐H Bond Activation

Selective C–H bond alkynylation toward modular access to material and pharmaceutical molecules is of great desire in modern organic synthesis. Disclosed herein is rhodium(III)‐catalyzed selective C–H bond mono‐/bialkynylation of 4‐aryl phthalazin‐1(2H)‐one was developed. The silver salt AgSbF6 are demonstrated to play a vital role in promoting the bialkynylation reactions. The present alkynylation strategy is simple, efficient, and features high functional group tolerance and broad substrate scope under an air atmosphere. Additionally, 6‐aryl pyridazin‐3(2H)‐one scaffold is amenable to the selective monoalkynylation and sequential bialkynylation, respectively.

Cyanomethylation of Substituted Fluorenes and Oxindoles with Alkyl Nitriles.

The first example of metal-free cyanomethylenation from alkyl nitriles of sp3 C-H bonds to afford quaternary carbon centers is described. This oxidative protocol is operationally simple and features good functional group compatibility. This method provides a novel approach to highly functionalized fluorene and oxindole derivatives, which are commonly used in material and pharmaceutical areas. Control experiments provide evidence of a radical reaction process.

Lewis Acid Catalyzed Electrophilic Aminomethyloxygenative Cyclization of Alkynols with N,O-Aminals.

Lewis acid enables the electrophilic carbooxygenative cyclization of alkynols with N,O-aminals. The new process proceeds efficiently under very mild conditions via a pathway that is opposite to classical carbo-metalation. These reactions exhibit broad substrate generality and functional group compatibility, leading to a wide variety of 5-8-membered oxacycles bearing diverse functional groups. The cyclization products can be elaborated via simple functional group transformations to generate synthetically useful oxacycles.

Urinalysis and Prenatal Health: Evaluation of a Simple Experiment That Connects Organic Functional Groups to Health Equity

Knowledge of functional groups provides students with a language for organic chemistry. However, students in a health science chemistry course do not plan to be synthetic organic chemists and, therefore, need examples of how functional group chemistry is relevant to their vocational goals. We have developed a lab to demonstrate how simple functional group chemistry is used in laboratory testing, namely, the “pee test”, or dipstick urinalysis. Dipstick urinalysis is frequently used to screen for various conditions and is used weekly in the last month of pregnancy. Our lab models the prenatal clinical environment. The laboratory allows for testing of chemical species that support a medical diagnosis: albumin testing for preeclampsia; leukocytes, nitrites, and pH for urinary tract infection; glucose, ketones, and pH to test for gestational diabetes, alcoholism, or other serious metabolic diseases. The related lessons are designed to support students in understanding the reactions involved in testing, biochemistry related to diagnosis, and general understandings of how tests are interpreted. In developing this experiment, we were confronted with disparities in prenatal care, namely, the absence of culturally competent care, inequitable access to care, and toxic stress due to racism that contribute to dramatically increased maternal death rates for women of color in the US. We identified resources to educate students on culturally competent care. These resources include reference to the way in which the “pee test” is administered. We have incorporated this resource into our lab with appropriate reflection questions, based on our newly devised cultural competence and social justice framework for chemistry students. Our findings indicated that student understandings of the chemistry and testing methods were adequate; on average, 77% of samples were properly diagnosed. With respect to social justice and cultural competence, we found that students predominantly discussed two elements of the cultural competence and social justice framework: reflection on privilege in society and agency to promote equity in healthcare.

Construction of Chiral 1,3-Diamines through Rhodium-Catalyzed Asymmetric Arylation of Cyclic N-Sulfonyl Imines.

A rhodium/sulfur-olefin complex catalyzed asymmetric 1,2-addition of arylboronic acids to six-membered 1,2,6-thiadiazinane 1,1-dioxide-type cyclic imines to access highly optically active sulfamides (95-99% ee) has been developed. By taking advantage of the simple functional group transformations, an interesting array of valuable chiral 1,3-diamines with different substitution patterns can be readily obtained in a highly enantioenriched manner.

Sulfur Betaines from S-Propargyl Xanthates. Unusual Chemistry from a Simple Functional Group

S-Propargyl xanthates undergo upon heating a [3,3] sigmatropic rearrangement followed by a reversible ring closure into a novel betaine. This betaine can be implicated in carbon–carbon bond forming processes, in the synthesis of esters, in the inversion of secondary alcohols, in the formation of alkenes, for the generation of rigid, cisoid dienes that are highly reactive in both inter- and intra-molecular Diels–Alder cycloadditions, and in various other synthetically useful transformations.1 Introduction2 An Unexpected Transformation3 Evidence for the Betaine Intermediate4 A Method for the Synthesis of Esters and for the Inversion of Secondary Alcohols5 A General Alkylation Process6 The Case of Carbon Acids7 A Synthesis of Alkenes8 Further Trapping Experiments. Concerted or Not Concerted?9 Rigid Cisoid Dienes10 Propargyl Radicals11 Concluding Remarks

N-ferrocenylphthalimide; A single redox couple formed by attaching a ferrocene moiety to phthalimide for non-aqueous flow batteries

N-ferrocenylphthalimide (FcPI) is prepared by replacing the hydrogen atom at the N-site of phthalimide with a ferrocene moiety. Phthalimide shows irreversible redox reaction due to H atom at the N-site of phthalimide. By replacing H atom of phthalimide with non-detachable functional group, such as alkyl group, redox reaction becomes reversible. Reversibility of redox reaction is requirement for redox couple due to cycling performance in battery system. In this work, electroactive group, not the simple functional group, is introduced to substitute H atom of phthalimide. As an electroactive group, ferrocenyl group has two main benefits. First, the redox reaction of the initial phthalimide with H atom at the N-site becomes reversible at E1/2 = −1.87 V (vs. Fc/Fc+) with an excellent stability. Second, FcPI is a single redox couple with Ecell = 1.94 V in a non-aqueous electrolyte because the ferrocene moiety in the molecule is also redox-active at E1/2 = 0.07 V (vs. Fc/Fc+) with stability. A non-flowing coin-type cell employing FcPI as a single redox couple exhibits an excellent Coulombic efficiency of 97.3% and stable cycle performance during the 50th cycle. Furthermore, rate test realizes fast charge transfer kinetics as voltage efficiency of 96.5–90.1% at 1.0–3.0 C.

Instilling exploitable INHIBIT logic gate response for F−/H+ in ‘end-off’ anthracene-diamine hybrid by simple functional group manipulation: Experimental study aided by DFT calculations

Two anthracene based receptors ADAMN and ANOPD were synthesized and characterized. The response of both towards F− ion has been monitored by UV–Vis and 1H NMR spectroscopy as well as naked eye color change. Interestingly, change in acceptor unit endows ADAMN to behave as a INHIBIT logic gate with F− and H+ as inputs whereas ANOPD remains totally silent towards F−. The reason for this differential behavior has been explored by DFT calculations. The practical utility of the logic gate response of ADAMN was explored by successful paper strip experiment.

Ruthenium-catalyzed umpolung carboxylation of hydrazones with CO2.

The first ruthenium-catalyzed umpolung carboxylation of hydrazones with CO2 to generate important aryl acetic acids is reported. Besides aldehyde hydrazones, a variety of ketone hydrazones, which have not been successfully applied in previous umpolung reactions with other reactive electrophiles, also show high reactivity and selectivity under mild conditions. Moreover, this operationally simple protocol features good functional group tolerance, is readily scalable, and offers easy derivation of important structures, including bioactive felbinac and adiphenine. Computational studies reveal that this umpolung reaction proceeds through the generation of a Ru-nitrenoid followed by concerted [4 + 2] cycloaddition with CO2.