Ligand-Enabled γ-C(sp3)–H Olefination of Free Carboxylic Acids

2020 ◽  
Author(s):  
Kiron Kumar Ghosh ◽  
Alexander Uttry ◽  
Francesca Ghiringhelli ◽  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Reaction Mechanism ◽  
Carboxylic Acids ◽  
Michael Addition ◽  
Kinetic Studies ◽  
Wide Range ◽  
Palladium Catalyzed

We report the ligand enabled C(sp3)–H activation/olefination of free carboxylic acids in the γ-position. Through an intramolecular Michael-addition, δ-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the γ-position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.<br>

Ligand-Enabled γ-C(sp3)–H Olefination of Free Carboxylic Acids

2020 ◽  
Author(s):  
Kiron Kumar Ghosh ◽  
Alexander Uttry ◽  
Francesca Ghiringhelli ◽  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Reaction Mechanism ◽  
Carboxylic Acids ◽  
Michael Addition ◽  
Kinetic Studies ◽  
Wide Range ◽  
Palladium Catalyzed

We report the ligand enabled C(sp3)–H activation/olefination of free carboxylic acids in the γ-position. Through an intramolecular Michael-addition, δ-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the γ-position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.<br>

scholarly journals Ligand-Enabled β-C(sp3)–H Lactonization: A Stepping Stone for General and Practical β-C–H Functionalizations

2019 ◽  
Author(s):  
Zhe Zhuang ◽  
jin-quan yu
Keyword(s):  
Carboxylic Acids ◽  
Amino Groups ◽  
Major Drawback ◽  
Aliphatic Acids ◽  
Amino Acid Ligand ◽  
Acid Ligand ◽  
Aryl Bromides ◽  
Wide Range ◽  
Palladium Catalyzed ◽  
Highly Strained

β-C–H functionalization of aliphatic acids is emerging as a valuable synthetic disconnection that complements a wide range of conjugate addition reactions. Despite two decades of effort on β-C–H functionalizations, reported reactions bear numerous challenges, especially for industrial-scale applications due to the use of expensive oxidants and poor scope. For example, arylation reactions are only compatible with aryl iodides but not the more practical aryl bromides and chlorides, alkylations are limited to primary alkyl coupling partners; fluorination and amination reactions have not been possible using free carboxylic acids as directing groups. The unselective formation of mono- and di-functionalized products is another major drawback. Herein, we report an unprecedented palladium-catalyzed β-C(sp<sup>3</sup>)–H lactonization of aliphatic acids enabled by a mono-<i>N</i>-protected β-amino acid ligand. The highly strained and reactive β-lactone products are versatile linchpins for the mono-selective installation of diverse alkyl, alkenyl, aryl, alkynyl, fluoro, hydroxyl, and amino groups at the β position of the parent acid, thus providing a one-for-all strategy to synthesize a myriad of carboxylic acids. The use of inexpensive <i>tert</i>-butyl hydrogen peroxide (TBHP) as the oxidant, as well as the ease of product purification without column chromatography renders this reaction amenable to ton-scale manufacturing.

scholarly journals Ligand-Enabled β-C(sp3)–H Lactonization: A Stepping Stone for General and Practical β-C–H Functionalizations

2019 ◽  
Author(s):  
Zhe Zhuang ◽  
jin-quan yu
Keyword(s):  
Carboxylic Acids ◽  
Amino Groups ◽  
Major Drawback ◽  
Aliphatic Acids ◽  
Amino Acid Ligand ◽  
Acid Ligand ◽  
Aryl Bromides ◽  
Wide Range ◽  
Palladium Catalyzed ◽  
Highly Strained

β-C–H functionalization of aliphatic acids is emerging as a valuable synthetic disconnection that complements a wide range of conjugate addition reactions. Despite two decades of effort on β-C–H functionalizations, reported reactions bear numerous challenges, especially for industrial-scale applications due to the use of expensive oxidants and poor scope. For example, arylation reactions are only compatible with aryl iodides but not the more practical aryl bromides and chlorides, alkylations are limited to primary alkyl coupling partners; fluorination and amination reactions have not been possible using free carboxylic acids as directing groups. The unselective formation of mono- and di-functionalized products is another major drawback. Herein, we report an unprecedented palladium-catalyzed β-C(sp<sup>3</sup>)–H lactonization of aliphatic acids enabled by a mono-<i>N</i>-protected β-amino acid ligand. The highly strained and reactive β-lactone products are versatile linchpins for the mono-selective installation of diverse alkyl, alkenyl, aryl, alkynyl, fluoro, hydroxyl, and amino groups at the β position of the parent acid, thus providing a one-for-all strategy to synthesize a myriad of carboxylic acids. The use of inexpensive <i>tert</i>-butyl hydrogen peroxide (TBHP) as the oxidant, as well as the ease of product purification without column chromatography renders this reaction amenable to ton-scale manufacturing.

Aerobic oxidation of 5-hydroxymethylfurfural to 2,5-diformylfuran on supported vanadium oxide catalysts: Structural effect and reaction mechanism

2011 ◽  
Vol 84 (3) ◽  
pp. 765-777 ◽  
Author(s):  
Junfang Nie ◽  
Haichao Liu
Keyword(s):  
Reaction Mechanism ◽  
Vanadium Oxide ◽  
Aerobic Oxidation ◽  
Kinetic Studies ◽  
Structural Effect ◽  
Monolayer Capacity ◽  
Rate Determining Step ◽  
Vis Spectroscopy ◽  
Wide Range ◽  
Support Surfaces

The structure–activity relationship and reaction mechanism for selective oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-diformylfuran (DFF) in toluene were studied on vanadium oxide domains on TiO2, Al2O3, Nb2O5, ZrO2, and MgO and with a wide range of VOx surface densities. The structures of these catalysts were characterized by X-ray diffraction (XRD), diffuse reflectance UV–vis spectroscopy (UV–vis DRS), and Raman spectroscopy, and their reducibility was probed by H2-temperature programmed reduction. The structures of the VOx domains evolved from monovanadate to polyvanadate structures with increasing the VOx surface densities, and finally to crystalline V2O5 clusters at surface densities above one-monolayer capacity. Within one-monolayer capacity, higher VOx surface densities and more reducible supports led to higher reducibility and reactivity of the VOx domains. The support surfaces covered with polyvanadates and V2O5 clusters and the supports with acidity favored the formation of DFF. The correlation between the reducibility and reactivity, together with the kinetic studies, suggests that the HMF oxidation to DFF proceeds via the redox mechanism involving the V5+/V4+ redox cycles and the reoxidation of V4+ to V5+ by O2 as the rate-determining step. These results may provide guidance for the design of more efficient catalysts for the HMF oxidation to synthesize DFF.

Palladium-catalyzed decarbonylative methylation of aryl carboxylic acids

2022 ◽  
Author(s):  
Boya Feng ◽  
Guodong Zhang ◽  
Xu Feng ◽  
Yu Chen
Keyword(s):  
Carboxylic Acids ◽  
Wide Range ◽  
Palladium Catalyzed

Described herein is a palladium-catalyzed decarbonylative methylation of aryl carboxylic acids using trimethylboroxine (TMB) as the methylating reagent. The Pd(OAc)2/XantPhos system is compatible with a wide range of carboxylic acids...

Arylation of enelactams using TIPSOTf: reaction scope and mechanistic insight

2021 ◽  
Author(s):  
Tomasz J. Idzik ◽  
Zofia M. Myk ◽  
Łukasz Struk ◽  
Magdalena Perużyńska ◽  
Gabriela Maciejewska ◽  
...  
Keyword(s):  
Reaction Mechanism ◽  
Multinuclear Nmr ◽  
Mechanistic Insight ◽  
Nmr Study ◽  
Wide Range

Triisopropylsilyltrifluoromethanesulfonate can be effectively used for the arylation of a wide range of enelactams. The multinuclear NMR study provided deep insights into the reaction mechanism.

Reversing Reactivity: Stereoselective Desulfurative β-O-Glycosylation of Anomeric Thiosugars with Carboxylic Acids Under Copper or Cobalt Catalysis

2019 ◽  
Author(s):  
Samir Messaoudi ◽  
Nedjwa Bennai ◽  
Amelie Chabrier ◽  
Maha Fatthalla ◽  
Expédite Yen-Pon ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Late Stage ◽  
Catalytic Amount ◽  
Broad Scope ◽  
Wide Range ◽  
Glycosylation Reaction

We have discovered a new mode of reactivity of 1-thiosugars in the presence of Cu(II) or Co(II) for a stereoselective <i>O</i>-glycosylation reaction. The process involves the use of a catalytic amount of Cu(acac)2 or Co(acac)2 and Ag2CO3 as an oxidant in α,α,α-trifluorotoluene (TFT). Moreover, this protocol turned out to have a broad scope, allowing to prepare a wide range of com-plex substituted <i>O</i>-glycoside esters in good to excellent yields with an exclusive β-selectivity. The late-stage modification of phar-maceuticals by this method was also demonstrated.

Stereospecific, Palladium-catalyzed C(sp3)–H Alkenylation and Alkynylation of a Proline Derivative Enabled by 8-Aminoquinoline as a Directing Group

2020 ◽  
Author(s):  
Aleksandra Balliu ◽  
Aaltje Roelofje Femmigje Strijker ◽  
Michael Oschmann ◽  
Monireh Pourghasemi Lati ◽  
Oscar Verho
Keyword(s):  
Carboxylic Acid ◽  
Building Blocks ◽  
Wide Range ◽  
Palladium Catalyzed ◽  
Directing Group ◽  
High Yields ◽  
Vinyl Iodides ◽  
Initial Results

<p>In this preprint, we present our initial results concerning a stereospecific Pd-catalyzed protocol for the C3 alkenylation and alkynylation of a proline derivative carrying the well utilized 8‑aminoquinoline directing group. Efficient C–H alkenylation was achieved with a wide range of vinyl iodides bearing different aliphatic, aromatic and heteroaromatic substituents, to furnish the corresponding C3 alkenylated products in good to high yields. In addition, we were able show that this protocol can also be used to install an alkynyl group into the pyrrolidine scaffold, when a TIPS-protected alkynyl bromide was used as the reaction partner. Furthermore, two different methods for the removal of the 8-aminoquinoline auxiliary are reported, which can enable access to both <i>cis</i>- and <i>trans</i>-configured carboxylic acid building blocks from the C–H alkenylation products.</p>

pH-Dependent Thermal Stability of Vibrio cholerae L-asparaginase

2019 ◽  
Vol 26 (10) ◽  
pp. 743-750 ◽  
Author(s):  
Remya Radha ◽  
Sathyanarayana N. Gummadi
Keyword(s):  
Vibrio Cholerae ◽  
Conformational Changes ◽  
Kinetic Studies ◽  
Structural Features ◽  
Structure Stability ◽  
Kcal Mole ◽  
Scanning Calorimetry ◽  
Wide Range ◽  
Ph Dependent ◽  
Ph Range

Background:pH is one of the decisive macromolecular properties of proteins that significantly affects enzyme structure, stability and reaction rate. Change in pH may protonate or deprotonate the side group of aminoacid residues in the protein, thereby resulting in changes in chemical and structural features. Hence studies on the kinetics of enzyme deactivation by pH are important for assessing the bio-functionality of industrial enzymes. L-asparaginase is one such important enzyme that has potent applications in cancer therapy and food industry.Objective:The objective of the study is to understand and analyze the influence of pH on deactivation and stability of Vibrio cholerae L-asparaginase.Methods:Kinetic studies were conducted to analyze the effect of pH on stability and deactivation of Vibrio cholerae L-asparaginase. Circular Dichroism (CD) and Differential Scanning Calorimetry (DSC) studies have been carried out to understand the pH-dependent conformational changes in the secondary structure of V. cholerae L-asparaginase.Results:The enzyme was found to be least stable at extreme acidic conditions (pH< 4.5) and exhibited a gradual increase in melting temperature from 40 to 81 °C within pH range of 4.0 to 7.0. Thermodynamic properties of protein were estimated and at pH 7.0 the protein exhibited ΔG37of 26.31 kcal mole-1, ΔH of 204.27 kcal mole-1 and ΔS of 574.06 cal mole-1 K-1.Conclusion:The stability and thermodynamic analysis revealed that V. cholerae L-asparaginase was highly stable over a wide range of pH, with the highest stability in the pH range of 5.0–7.0.

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