Selective Addition Reactions Research Articles

Spiroannulations of β-Ketothioamides with Bromoenals via Selective C-Michael Addition and S-Michael Addition-Triggered Cascade Reactions.

A spiroannulation reaction of β-ketothioamides with aromatic β-bromoenals and aromatic α-bromoenals via selective C-Michael addition and S-Michael addition-triggered cascade reactions has been developed. This protocol provides a novel and rapid approach for the synthesis of substituted spirothiopyran and spirothiophene derivatives under mild conditions with moderate to good yields and a broad substrate scope.

Design and synthesis of a novel fluorescent probe for the detection of bisulfite in plant and zebrafish

Sulfur dioxide (SO2) and its derivative bisulfite (SO32−/HSO3−) have a serious impact on the human health and environment. Therefore, the development of highly sensitive and specific detection methods for SO2 and its derivative is of great significance for environmental monitoring, food safety, and related disease research. In this paper, probe TPN-DP based on the triphenylamine fluorophore was developed to enable the imaging and detection of HSO3− in plant and zebrafish. In PBS buffer solution, the designed probe TPN-DP can react with HSO3− by highly selective nucleophilic addition reaction, leading to a sensitive change in the color of probe TPN-DP solution from pink to colorless. The changes in fluorescence and color can be easily recognized by the naked eye. Moreover, probe TPN-DP exhibited a fast response time of 8 min, high sensitivity of 19.4 nM, and excellent selectivity for sensing HSO3−. With the help of probe TPN-DP, the detection of HSO3− was successfully achieved in water sample and various biological systems, including onion epidermal cells, tobacco seedling roots, and zebrafish. These findings not only provide valuable insights into the biological role of HSO3− but also offer a promising analytical method for efficient HSO3− recognition.

Postpolymerization Modification and Topological Structure Design of Poly(vinyl ether)s Based on the Selective Addition Reaction of Electrophilic Selenium Reagent and Divinyl Monomers

Postpolymerization Modification and Topological Structure Design of Poly(vinyl ether)s Based on the Selective Addition Reaction of Electrophilic Selenium Reagent and Divinyl Monomers

Polymers from organosilicon derivatives of 5-norbornene-2-methanol for membrane gas separation

In this work, we have proposed a new strategy to the synthesis of norbornene-type monomers with Si–O–C structural motifs via a straightforward and selective dehydrogenative addition reaction between 5-norbornene-2-methanol and trialkylsilanes. As a result, a set of monomers with various trilalkylsiloxy groups (alkyl – CH3, C2H5, and n-C3H7) was synthesized with the yields of 89–90%. These monomers exhibited a high reactivity in both metathesis and vinyl-addition polymerization, affording high-molecular-weight products in yields up to 90%. The metathesis polymers were rubbery with glass transition temperatures from −29 to +23 °C, while related isomeric vinyl-addition polynorbornenes were glassy polymers. Permeability (P) and diffusion (D) coefficients for these polymers were systematically evaluated for permanent gases (He, H2, O2, N2, and CO2) and C1–C4 alkanes. Studying their gas transport properties allowed to establish new structure-property relationships. Particularly, the length of alkyl fragments in trilalkylsiloxy group affected differently gas permeability of metathesis (rubbery) and vinyl-addition (glassy) polymers. Besides, it was shown that the method of linking the Si–O–C-containing group to the main chains of polymers played very important role: Alk3SiO-substituted polynorbornenes are more permeable than isomeric (AlkO)Alk2Si-substituted ones. For the metathesis polynorbornenes, P(CO2) were in the range of 152–226 Barrer, and ideal selectivity (α) of CO2/N2 – 13-16; for the vinyl-addition polynorbornenes, P(CO2) = 230–500 Barrer, and α(CO2/N2) = 14–17. Among studied polymers, promising results for ethane/methane separation was demonstrated by metathesis polynorbornene bearing tri(n-propyl)siloxymethyl substituents: P(C2H6) = 138 Barrer and α(C2H6/CH4) = 2.4. The obtained polymers were also characterized by using TGA, WAXD, and nitrogen adsorption-desorption methods.

Introverted Brønsted acid cavitands for selective conjugate addition reactions

ABSTRACT Four new quinoxaline-spanned cavitands having a diester hydrogen phosphate group were successfully synthesised. These phosphorous derivatives were applied in Brønsted acid-assisted catalytic conjugate addition reactions. The results were ranked with the control of diphenyl hydrogen phosphate as well as among those four cavitands. The structure–activity relationship revealed that the catalyst centre surrounded by two trans-positioned quinoxalines significantly influences reaction profile and product distribution. This comparative study provides us an intellectual basis for future catalytic cavitand chemistry and artificial enzymatic catalysis.

Ynamide-Mediated Thionoester and Dithioester Syntheses.

A novel ynamide-mediated synthesis of thionoesters and dithioesters is described. The selective addition reactions of various monothiocarboxylic acids with ynamide furnish α-thioacyloxyenamides, which undergo transesterification with nucleophilic -OH or -SH species to afford thionoesters and dithioesters, respectively. The broad substrate scope, mild reaction conditions, and excellent yields make this method an attractive synthetic approach to thionoesters and dithioesters.

Selective addition reactions of difluoromethyltriazoles to ketones and aldehydes without the formation of difluorocarbene

There has been great interest in the chemistry, syntheses and reactivities of heteroaryl-N-difluoromethane. The present work is based on the addition reaction of difluoromethyl anions, which are generated directly from difluoromethyl heterocycles, to benzophenone and benzaldehyde. As 1,2,3-triazoles and benzotriazoles can act as leaving groups, two reaction pathways are expected to exist: either the desired reaction route - deprotonation (formation of difluoromethyl anion) or the unfavored reaction route – the formation of difluorocarbene. We describe the chemistry for the selective addition reactions of difluoromethyltriazoles to ketones and aldehydes without the formation of difluorocarbene. Addition reactions of 1-(difluoromethyl)-1H-benzotriazole 1 to benzophenone 2 using potassium t-butoxide as a base were found to proceed smoothly at 0 °C for 5 min with high yields (80–88%). A plausible mechanism for the addition reactions of 1-(difluoromethyl)-1H-benzotriazole 1 and 1-difluoromethyl-4-phenyltriazole 5 to benzophenones and benzaldehydes is proposed based on deuterium-quenching experiments.

Exploring the abundance of oleate hydratases in the genus Rhodococcus\u2014discovery of novel enzymes with complementary substrate scope

Oleate hydratases (Ohys, EC 4.2.1.53) are a class of enzymes capable of selective water addition reactions to a broad range of unsaturated fatty acids leading to the respective chiral alcohols. Much research was dedicated to improving the applications of existing Ohys as well as to the identification of undescribed Ohys with potentially novel properties. This study focuses on the latter by exploring the genus Rhodococcus for its plenitude of oleate hydratases. Three different Rhodococcus clades showed the presence of oleate hydratases whereby each clade was represented by a specific oleate hydratase family (HFam). Phylogenetic and sequence analyses revealed HFam-specific patterns amongst conserved amino acids. Oleate hydratases from two Rhodococcus strains (HFam 2 and 3) were heterologously expressed in Escherichia coli and their substrate scope investigated. Here, both enzymes showed a complementary behaviour towards sterically demanding and multiple unsaturated fatty acids. Furthermore, this study includes the characterisation of the newly discovered Rhodococcus pyridinivorans Ohy. The steady-state kinetics of R. pyridinivorans Ohy was measured using a novel coupled assay based on the alcohol dehydrogenase and NAD+-dependent oxidation of 10-hydroxystearic acid.

Selective Hydride Addition Reaction in Ester vs. Amide Chemical Functional Group

Cancer is among the leading causes of death in the United States. In fact, according to the Center for Disease Control, there was 599,108 cancer-related deaths in the year 2017. In addition to having a high mortality rate, the cost of cancer care has also continued to climb over the years and is estimated to reach 173 billion in 2020, according to the National Institute of Health. With that being said, more research and studies are needed to be conducted to find a more effective and inexpensive alternative, to contribute to the treatment of cancer. Natural products (NPs) have proven to be promising in drug discovery, particularly in the development of anti-cancer therapy. Therefore, in our research lab, we are interested in contributing to the development of a tripeptide natural product that could be used in oncology therapy. In fact, the main objective of this study is to evaluate the selective hydride addition reaction on those two functional groups which is a part of on-going synthetic NP synthesis of bio-active tripeptide. My senior project is involved with two chemical steps which is 1) Coupling reaction and 2) Hydride additional reaction. Thus far, we have successfully synthesized dipeptide and analytical data such as MS and NMR are presented in this poster with the most current update on this project on the hydride addition reaction. The outcome of this project provides us with the feasibility of possible NP peptide synthesis and a possible anti-cancer relevant analog development.

A novel phenylalanine ammonia-lyase from Pseudozyma antarctica for stereoselective biotransformations of unnatural amino acids

A novel phenylalanine ammonia-lyase of the psychrophilic yeast Pseudozyma antarctica (PzaPAL) was identified by screening microbial genomes against known PAL sequences. PzaPAL has a significantly different substrate binding pocket with an extended loop (26 aa long) connected to the aromatic ring binding region of the active site as compared to the known PALs from eukaryotes. The general properties of recombinant PzaPAL expressed in E. coli were characterized including kinetic features of this novel PAL with l-phenylalanine (S)-1a and further racemic substituted phenylalanines rac-1b-g,k. In most cases, PzaPAL revealed significantly higher turnover numbers than the PAL from Petroselinum crispum (PcPAL). Finally, the biocatalytic performance of PzaPAL and PcPAL was compared in the kinetic resolutions of racemic phenylalanine derivatives (rac-1a-s) by enzymatic ammonia elimination and also in the enantiotope selective ammonia addition reactions to cinnamic acid derivatives (2a-s). The enantiotope selectivity of PzaPAL with o-, m-, p-fluoro-, o-, p-chloro- and o-, m-bromo-substituted cinnamic acids proved to be higher than that of PcPAL.

Highly Specific Cys Fluorescence Probe for Living Mouse Brain Imaging via Evading Reaction with Other Biothiols.

Depression is characterized by oxidative stress in the brain. As the crucial reductive biothiol, cysteine (Cys) directly regulates the occurrence of oxidative stress in the brain. Despite its significance, the precise exploration of Cys in mouse brains remains a challenge, primarily owing to the limitations of Cys-monitoring tools, especially the interference from unavoidable reaction with other biothiols. Thus, we developed a novel two-photon fluorescence probe for Cys based on a new specific recognition site, thiobenzoate. Encountering Cys, the carbon-sulfur double bond in the probe formed a stable five-membered ring via the selective nucleophilic addition reaction, triggering a remarkable fluorescence increase. Notably, this reaction cannot occur with other biothiols, which afford the probe unprecedented selectivity to Cys. With two-photon excitation at 754 nm, we achieved in situ visualization of the increased Cys in PC12 cells under dithiothreitol stimulation. Furthermore, we directly visualized the precipitous reduction of Cys in the brains of mice with depression phenotypes for the first time. This work opens up new vistas for Cys imaging and expands the understanding of pathogenesis of depression.

Selective Double Addition Reaction of an E‒H Bond (E = Si, B) to a C≡N Triple Bond of Organonitriles.

The catalytic double hydrometalation such as hydrosilylation and hydroborylation of organonitriles has attracted considerable attention because the obtained products are widely used in organic synthesis and it is thought to be one of the effective methods for reduction of organonitriles. However, the examples of these reactions are quite limited to date. This paper summarizes the development of selective double hydrosilylation, double hydroborylation, and dihydroborylsilylation of organonitriles, including their reaction mechanisms and the role of the metal species in the catalytic cycle.

Facile Phenylphosphinidene Transfer Reactions from Carbene-Phosphinidene Zinc Complexes.

Phosphinidenes [R-P] are convenient P1 building blocks for the synthesis of a plethora of organophosphorus compounds. Thus far, transition-metal-complexed phosphinidenes have been used for their singlet ground-state reactivity to promote selective addition and insertion reactions. One disadvantage of this approach is that after transfer of the P1 moiety to the substrate, a challenging demetallation step is required to provide the free phosphine. We report a simple method that enables the Lewis acid promoted transfer of phenylphosphinidene, [PhP], from NHC=PPh adducts (NHC=N-heterocyclic carbene) to various substrates to produce directly uncoordinated phosphorus heterocycles that are difficult to obtain otherwise.

Facile Phenylphosphinidene Transfer Reactions from Carbene–Phosphinidene Zinc Complexes

AbstractPhosphinidenes [R‐P] are convenient P1 building blocks for the synthesis of a plethora of organophosphorus compounds. Thus far, transition‐metal‐complexed phosphinidenes have been used for their singlet ground‐state reactivity to promote selective addition and insertion reactions. One disadvantage of this approach is that after transfer of the P1 moiety to the substrate, a challenging demetallation step is required to provide the free phosphine. We report a simple method that enables the Lewis acid promoted transfer of phenylphosphinidene, [PhP], from NHC=PPh adducts (NHC=N‐heterocyclic carbene) to various substrates to produce directly uncoordinated phosphorus heterocycles that are difficult to obtain otherwise.

Stereocomplementary Routes to Hydroxylated Nitrogen Heterocycles: Total Syntheses of Casuarine, Australine, and 7‐epi‐Australine

Addition of lithiated 1-benzyloxyallene to a D-arabinose-derived cyclic nitrone occurred with perfect diastereoselectivity furnishing a bicyclic 1,2-oxazine derivative, which is an excellent precursor for pyrrolizidine alkaloids hydroxylated at C-7 with optional configuration at this stereogenic center. Depending on the stage of the N-O bond cleavage and ring re-closure, 7-hydroxypyrrolizidines with 7R or 7S configuration were obtained, as a result of completely selective addition reactions occurring complementarily at the bottom or top face of the endocyclic C-C double bond in six- and five-membered B rings, respectively. Applicability of these stereodivergent routes to obtain polyhydroxy pyrrolizidine alkaloids is demonstrated by the efficient syntheses of casuarine and australine as examples of the two classes of diversely configured 7-hydroxypyrrolizidine alkaloids. An alternative synthesis of australine and two strategies for the preparation of 7-epi-australine are also reported, which demonstrate that the stereoselectivity of hydride reduction of an exocyclic C-O double bond is independent of the ring size, occurring preferentially from the top face either in a six- or five-membered ring.

Multifunctional Macrocyclic Receptors as Templates for Aromatic Amino Acids: A Rare Example of a Highly Selective Multi-Input Multi-Output Chemo-"Logic Gate".

Proton-bound [M⋅H⋅G]+ diastereomeric complexes between some chiral aromatic amino acids or dipeptides (G) and a chiral multifunctional macrocyclic receptor (M=Chirabite-A) undergo, in the gas phase, highly selective substitution and addition reactions by amines, such as 2-aminobutane and piperidine. All the [M⋅H⋅G]+ complexes follow time-dependent monoexponential decays. In some cases, the kinetic curves exhibit a plateau revealing the presence of unreactive [M⋅H⋅G]+ structures. In them, the amino acid is accommodated in the macrocycle cavity in the zwitterionic form by sharing its acidic hydrogen atoms with the pyridine nitrogen atoms of the host. The same interactions are structurally inaccessible to G=dipeptides or monofunctional amines, which then can be readily released from [M⋅H⋅G]+ . When the amino acid interacts with the amidocarbonyl oxygen atoms pointing outside the macrocycle cavity, it saves the canonical structure and can be readily displaced by the amine. The Chirabite-A may act as an efficient template for aromatic amino acids by releasing them or not depending upon the amino acid configuration and the basicity of the amine. These unique properties confer to the gas-phase diastereomeric [M⋅H⋅G]+ complexes the features of multi-input multi-output chemo-"logic gates".

Determination of critical micelle concentration of dendritic surfactant synthesized via a selective ring-opening addition reaction

An azetidine-2,4-dione was applied to synthesize dendrons with four carbons in the end ([G-0.5]-C4 and [G-1]-C4) via a selective ring-opening addition reaction, which was subsequently extended to obtain a dendritic surfactant ([G-1]-C4 surfactant) by acidification. The dendrons were characterized by Fourier transform infrared (FT-IR), 1H nuclear magnetic resonance (1H NMR), elemental analyzer (EA), and fast atom bombardment mass spectrometry (FAB MS). The dendritic surfactant, with a cationic head and branched hydrophobic C4 tails, was dissolved in 2wt.% dimethyl sulfoxide (DMSO) aqueous solution for the determination of critical micelle concentration (CMC) by fluorescence and electrical conductivity measurements. The resulted CMC values were very close within measurements, ca. 0.013–0.05mM. Transmission electron microscopy (TEM) and zeta potential measurement also provided an evidence of micelle formation and shape. Moreover, anionic dyes were adsorbed onto the micelles successfully to confirm the positive charge of [G-1]-C4 surfactant.

Bio-polymer starch thin film sensors for low concentration detection of cyanide anions in water

Abstract Starch films containing a chemodosimeter probe based on a quinolinium merocyanine dye were successfully prepared and studied. Through the selective nucleophilic addition reaction between cyanide anions and the dye chromophore the film can selectively detect sub-micromolar quantities of cyanide ion by a distinct color change.

Selective and CO-Retentive Addition Reactions of Acid Chlorides to Terminal Alkynes in Synthesis of β-Chloro-α,β-unsaturated Ketones Using ZnO

Abstract The addition reaction of acid chlorides with terminal alkynes to afford β-chloro-α,β-unsaturated ketones using ZnO as catalyst has been studied under solvent-free conditions. All the reactions were done at room temperature and β-chloro-α,β-unsaturated ketones were obtained with selectivity in high yields.

ChemInform Abstract: Ruthenium‐Catalyzed Direct Arylations Through C—H Bond Cleavages

AbstractReview: 93 refs.