Pd(II)-catalyzed enantioselective C(sp3)–H arylation of cy-clopropanes and cyclobutanes guided by tertiary alkyla-mines.

ABSTRACT: Strained aminomethyl-cycloalkanes are a recurrent scaffold in medicinal chemistry due to their unique structural features that give rise to a range of biological properties. Here, we report a palladium-catalyzed enantioselective C(sp3)–H arylation of aminome-thyl-cyclopropanes and -cyclobutanes with aryl boronic acids. A range of native tertiary alkylamine groups are able to direct C–H cleavage and forge carbon-aryl bonds on the strained cycloalkanes framework as single diastereomers and with excellent enantiomeric ratios. Cen-tral to the success of this strategy is the use of a simple N-acetyl amino acid ligand, which not only controls the enantioselectivity but also promotes -C–H activation of over other pathways. Computational analysis of the cyclopalladation step provides an understanding of how enantioselective C–H cleavage occurs and revealed distinct transition structures to our previous work on enantioselective desymme-trization of N-iso-butyl tertiary alkylamines. This straightforward and operationally simple method simplifies the construction of func-tionalized aminomethyl-strained cycloalkanes, which we believe will find widespread use in academic and industrial settings relating to the synthesis of biologically active small molecules.

Corrosion Inhibition Studies of Benzilic Acid-Tyrosine Ligand and their Metal Complexes

A novel amino acid ligand derived from Benzilic acid and Tyrosine and its Cr (II), Fe (III), Co (II) and Ni (II) transition metal complexes were synthesized. The structure elucidation of the ligand and its complexes were derived on the basis of various spectroscopic methods such as Infrared and electronic spectra along with the aid of CHN, magnetic and conductometric measurements1, 2, 3. The corrosion inhibition efficiency of newly synthesized amino acid-mixed ligand and their metal complexes were studied in 0.5M HCl solution. The results show that the inhibitors exhibits an inhibition efficiency of 40-67% at 200ppm.The ligand shows the maximum efficiency whereas on complexation the efficiency tend to decrease. When the concentration of the inhibitor increases, then the efficiency of the inhibitor will increase4. The adsorption studies reveal that iron complex with the mild steel is chemisorption and the thermodynamic parameters such as adsorption, equilibrium constant (K) and free energy of adsorption (∆Gads) were calculated. The curve of the adsorption fits well with Langmuir adsorption isotherm.

Rapid Construction of Tetralin, Chromane, and Indane Motifs via Cyclative C−H/C−H Coupling: Four-Step Total Synthesis of (±)-Russujaponol F

The development of practical C−H/C−H coupling reactions remains a challenging yet appealing synthetic venture because it circumvents the need to prefunctionalize both coupling partners for the generation of C−C bonds. Herein, we report a cyclative C(sp³)−H/C(sp²)−H coupling reaction of free aliphatic acids enabled by a cyclopentane-based mono-<i>N</i>-protected β-amino acid ligand. This reaction uses inexpensive sodium percarbonate (Na₂CO₃·1.5H₂O₂) as the sole oxidant, generating water as the only byproduct. A range of biologically important scaffolds, including tetralins, chromanes, and indanes, could be easily prepared by this protocol. Finally, the synthetic application of this methodology is demonstrated by the concise total synthesis of (±)-russujaponol F in a four-step sequence starting from readily available phenylacetic acid and pivalic acid through the sequential functionalizations of four C−H bonds.

Rapid Construction of Tetralin, Chromane, and Indane Motifs via Cyclative C−H/C−H Coupling: Four-Step Total Synthesis of (±)-Russujaponol F

The development of practical C−H/C−H coupling reactions remains a challenging yet appealing synthetic venture because it circumvents the need to prefunctionalize both coupling partners for the generation of C−C bonds. Herein, we report a cyclative C(sp³)−H/C(sp²)−H coupling reaction of free aliphatic acids enabled by a cyclopentane-based mono-<i>N</i>-protected β-amino acid ligand. This reaction uses inexpensive sodium percarbonate (Na₂CO₃·1.5H₂O₂) as the sole oxidant, generating water as the only byproduct. A range of biologically important scaffolds, including tetralins, chromanes, and indanes, could be easily prepared by this protocol. Finally, the synthetic application of this methodology is demonstrated by the concise total synthesis of (±)-russujaponol F in a four-step sequence starting from readily available phenylacetic acid and pivalic acid through the sequential functionalizations of four C−H bonds.

Spin-frustration with two quasi-degenerated spin states of a copper(ii) heptanuclear complex obtained from an amino acid ligand

A Cu(ii) heptanuclear complex, Cu7atac, synthesized from an amino acid ligand showed to be an antiferromagnetic spin-frustrated bis-triangular system. Cu7atac might be a promising qubit candidate for quantum information storage.

The structural bases for agonist diversity in anArabidopsis thalianaglutamate receptor-like channel

Arabidopsis thalianaglutamate receptor-like (GLR) channels are amino acid-gated ion channels involved in physiological processes including wound signaling, stomatal regulation, and pollen tube growth. Here, fluorescence microscopy and genetics were used to confirm the central role of GLR3.3 in the amino acid-elicited cytosolic Ca2+increase inArabidopsisseedling roots. To elucidate the binding properties of the receptor, we biochemically reconstituted the GLR3.3 ligand-binding domain (LBD) and analyzed its selectivity profile; our binding experiments revealed the LBD preference forl-Glu but also for sulfur-containing amino acids. Furthermore, we solved the crystal structures of the GLR3.3 LBD in complex with 4 different amino acid ligands, providing a rationale for how the LBD binding site evolved to accommodate diverse amino acids, thus laying the grounds for rational mutagenesis. Last, we inspected the structures of LBDs from nonplant species and generated homology models for other GLR isoforms. Our results establish that GLR3.3 is a receptor endowed with a unique amino acid ligand profile and provide a structural framework for engineering this and other GLR isoforms to investigate their physiology.

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

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(sp³)–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.

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

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(sp³)–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.