C‐S cross‐coupling reaction using novel and green synthesized CuO nanoparticles assisted by Euphorbia maculata extract

In the present study, biosynthesis of CuO nanoparticles using a rapid, eco‐friendly, cost‐effective and efficient method has been reported employing aqueous Euphorbia maculata extract as mild, renewable and non‐toxic reducing and capping agents without adding any surfactants. The biogenic and green method has some benefits compared to conventional physical and chemical methods. It is simple, cheap and environmentally friendly. The biosynthesized CuO NP displayed a color change pattern (from sky blue to black) on preparation and presented its respective broad peak at 365 nm, which was analyzed by UV–Vis spectroscopy. Using the FT‐IR analysis, biomolecules in E. maculata extract which are responsible for bioreduction activity and synthesize of CuO NP, were identified. The XRD, EDX and FESEM results confirmed the successful synthesis of CuO nanoparticles of 18 nm sizes, with spherical and sponge crystal structure. The catalytic activity of biosynthesized CuO NPs was studied in C‐S cross‐coupling reaction. This method has the advantages of high yields, easy work‐up, and simple reusability. The recovered CuO NP can be reused four times without any considerable loss of its catalytic activity.     

Screening of Three Transition Metal‐Mediated Reactions Compatible with DNA‐Encoded Chemical Libraries

The construction of DNA‐encoded chemical libraries (DECLs) crucially relies on the availability of chemical reactions, which are DNA‐compatible and which exhibit high conversion rates for a large number of diverse substrates. In this work, we present our optimization and validation procedures for three copper and palladium‐catalyzed reactions (Suzuki cross‐coupling, Sonogashira cross‐coupling, and copper(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC)), which have been successfully used by our group for the construction of large encoded libraries.     

Copper-Catalyzed Trifunctionalization of Alkynes: Rapid Formation of Oxindoles Bearing Geminal Diboronates

A copper-catalyzed trifunctionalization of alkynes that provides rapid access to oxindoles bearing a geminal diboronate side chain, highlighted by the simultaneous formation of one C−C bond and two C−B bonds, is reported. This new reaction features simple reaction conditions (ligand-free catalysis), a general substrate scope, and excellent chemoselectivity. Mechanistic study revealed a reaction sequence constituted by, in the order, borylation, intramolecular cross-coupling, hydroboration, which has been rarely documented.     

Designing Cross-Coupling Reactions using Aryl(trialkyl)silanes

Organo(trialkyl)silanes have several advantages, including high stability, low toxicity, good solubility, easy handling, and ready availability compared with heteroatom-substituted silanes. However, methods for the cross-coupling of organo(trialkyl)silanes are limited, most probably because of their exceeding robustness. Thus, a practical method for the cross-coupling of organo(trialkyl)silanes has been a long-standing challenging research target. This article discusses how aryl(trialkyl)silanes can be used in cross-coupling reactions. A pioneering example is Cu^II catalytic conditions with the use of electron-accepting aryl- or heteroaryl(triethyl)silanes and aryl iodides. The reaction forms biaryls or teraryls. This design concept can be extended to Pd/Cu^II-catalyzed cross-coupling polymerization reactions between such silanes and aryl bromides or chlorides and to Cu^I-catalyzed alkylation using alkyl halides.     

Catalytic C−H/C−F Coupling of Azoles and Acyl Fluorides

A method for the palladium/copper-catalyzed direct acylation of azoles with acyl fluorides is described. This study reports the first examples of acyl fluorides being used as acylation reagents in transition-metal-catalyzed aromatic C−H bond functionalization reactions. Depending on the reaction temperature, decarbonylative coupling may also occur. Mechanistic studies suggest that the cleavage of the aromatic C−H bond, promoted by a copper-phosphine species, is not the rate-limiting step of this acylation.     

Copper quinolate: A simple and efficient catalytic complex for coupling reactions

We describe an effective and novel method to prepare N-aryl imidazoles via the copper quinolate-catalyzed N-arylation of aryl halides and imidazoles. A wide range of products were obtained in moderate to excellent yields under the optimal reaction conditions. Applying standard conditions, the model reaction could be performed on a gram scale. This method also presents a new avenue to the “click” reaction of terminal alkynes, benzyl bromide, and sodium azide and to the construction of C–C bonds by homocoupling of phenylboronic acid or phenylacetylene derivatives with the aid of copper quinolate.     

Single-Step N-Terminal Modification of Proteins via a Bio-Inspired Copper(II)-Mediated Aldol Reaction

The chemical modification of proteins is an effective technique for manipulating the properties and functions of proteins, and for creating protein-based materials. The N-terminus is a promising target for single-site modification that provides modified proteins with uniform structures and properties. In this paper, a copper(II)-mediated aldol reaction with 2-pyridinecarboxaldehyde (2-PC) derivatives is proposed as an operationally simple method to selectively modify the N-terminus of peptides and proteins at room temperature and physiological pH. The copper(II) ion activates the N-terminal amino acids by complexation with an imine of the N-terminal amino acid and 2-PCs, realizing the selective formation of the nucleophilic intermediate at the N-terminus. This results in a stable carbon-carbon bond between the 2-PCs and the α-carbon of various N-terminal amino acids. The reaction is applied to four different proteins, including biopharmaceuticals such as filgrastim and trastuzumab. The modified trastuzumab retains the human epidermal growth factor receptor 2 recognition activity.     

Copper-Catalyzed Regioselective [3+3] Annulations of Alkynyl Ketimines with α-Cyano Ketones: the Synthesis of Polysubstituted 4H-Pyran Derivatives with a CF3-Containing Quaternary Center

Regioselective [3+3] annulation of alkynyl ketimines with α-cyano ketones for the synthesis of polysubstituted 4H-pyran derivatives with a quaternary CF₃-containing center has been realized by using Cu(OAc)₂ as the catalyst. The novel strategy tolerates a wide range of α-CF₃ alkynyl ketimines and α-cyano ketones with both aryl and alkyl substitutents. A preliminary asymmetric synthesis of chiral product 3 has been attempted by using copper and chiral thiourea as the cocatalyst with excellent yields (86-99 %) and good enantioselectivities (71–78 % ee). Furthermore, product 3 aa could be obtained on a gram-scale reaction with 75 % yield and 99 % ee after recrystallization. Several products were also transformed readily. Control experiments indicate that the reaction involves a process with a base-catalyzed or chiral thiourea-catalyzed Mannich-type reaction followed by a highly regioselective copper-catalyzed ring-closing reaction on the alkynyl moiety in a 6-endo-dig fashion.     

Copper‐Catalyzed Difunctionalization of Activated Alkynes by Radical Oxidation–Tandem Cyclization/Dearomatization to Synthesize 3‐Trifluoromethyl Spiro[4.5]trienones

A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent sodium trifluoromethanesulfinate (NaSO₂CF₃ or Langlois’ reagent) has been developed incorporating a tandem cyclization/dearomatization process. This strategy affords a straightforward route to synthesis of 3‐(trifluoromethyl)‐spiro[4.5]trienones, and presents an example of difunctionalization of alkynes for simultaneous formation of two carbon–carbon single bonds and one carbon–oxygen double bond.     

Formation and Reactivity of Organo‐Functionalized Tin Selenide Clusters

Reactions of R¹SnCl₃ (R¹=CMe₂CH₂C(O)Me) with (SiMe₃)₂Se yield a series of organo‐functionalized tin selenide clusters, [(SnR¹)₂SeCl₄] ( 1 ), [(SnR¹)₂Se₂Cl₂] ( 2 ), [(SnR¹)₃Se₄Cl] ( 3 ), and [(SnR¹)₄Se₆] ( 4 ), depending on the solvent and ratio of the reactants used. NMR experiments clearly suggest a stepwise formation of 1 through 4 by subsequent condensation steps with the concomitant release of Me₃SiCl. Furthermore, addition of hydrazines to the keto‐functionalized clusters leads to the formation of hydrazone derivatives, [(Sn₂(μ‐R³)(μ‐Se)Cl₄] ( 5 , R³=[CMe₂CH₂CMe(NH)]₂), [(SnR²)₃Se₄Cl] ( 6 , R²=CMe₂CH₂C(NNH₂)Me), [(SnR⁴)₃Se₄][SnCl₃] ( 7 , R⁴=CMe₂CH₂C(NNHPh)Me), [(SnR²)₄Se₆] ( 8 ), and [(SnR⁴)₄Se₆] ( 9 ). Upon treatment of 4 with [Cu(PPh₃)₃Cl] and excess (SiMe₃)₂Se, the cluster fragments to form [(R¹Sn)₂Se₂(CuPPh₃)₂Se₂] ( 10 ), the first discrete Sn/Se/Cu cluster compound reported in the literature. The derivatization reactions indicate fundamental differences between organotin sulfide and organotin selenide chemistry.