Determination of the absolute configuration and identity of chiral carboxylic acids using a Cu(II) complex of pyridine–benzimidazole-based ligand

We report a new achiral Cu host [Cu(bmb–bpy)(H₂O)(OTf)₂] (bmb–bpy = 6,6′-bis[((1-methylbenzimidazol-2-yl)thio)methyl]-2,2′-bipyridine) for the enantioselective and chemoselective recognition of chiral carboxylic acids. The binding of chiral carboxylic acids to [Cu(bmb–bpy)(H₂O)(OTf)₂] produced an exciton-coupled circular dichroism signal; the linear discriminant analysis allowed the assignment of the absolute configuration, enantiomeric excess, and identity of chiral carboxylic acids.     

An effective method for the synthesis of carboxylic esters and lactones using substituted benzoic anhydrides with Lewis acid catalysts

An efficient mixed-anhydride method for the synthesis of carboxylic esters and lactones using benzoic anhydride having electron withdrawing substituent(s) is developed by the promotion of Lewis acid catalysts. In the presence of a catalytic amount of TiCl₂(ClO₄)₂, various carboxylic esters are prepared in high yields through the formation of the corresponding mixed-anhydrides from 3,5-bis(trifluoromethyl)benzoic anhydride and carboxylic acids. The combined catalyst consisting of TiCl₂(ClO₄)₂ together with chlorotrimethylsilane functions as an effective catalyst for the synthesis of carboxylic esters from free carboxylic acids and alcohols with 4-(trifluoromethyl)benzoic anhydride. Various macrolactones are prepared from the free ω-hydroxycarboxylic acids by the combined use of 4-(trifluoromethyl)benzoic anhydride and titanium(IV) catalysts together with chlorotrimethylsilane under mild reaction conditions. The lactonization of trimethylsilyl ω-(trimethylsiloxy)carboxylates using 4-(trifluoromethyl)benzoic anhydride is also promoted at room temperature in the presence of a catalytic amount of TiCl₂(ClO₄)₂. An 8-membered ring lactone, a synthetic intermediate of cephalosporolide D, is successfully synthesized according to this mixed-anhydride method using 4-(trifluoromethyl)benzoic anhydride by the promotion of a catalytic amount of Hf(OTf)₄.     

Copper-catalysed intramolecular O-H addition to unactivated alkenes

Intramolecular cyclisation of ω-alkenoic acids and alkenols can be achieved using a catalytic amount of Cu(OTf)₂ to afford lactones and cyclic ethers, offering a practical alternative to existing catalysts.     

6-endo-dig Cyclization of heteroarylesters to alkynes promoted by Lewis acid catalyst in the presence of Brønsted acid

We report a regiocontrolled 6-endo-dig cyclization of 2-(2-arylethynyl)heteroaryl esters occurred under Brønsted acidic conditions and in the presence of a catalytic amount of Lewis acids such as Cu(OTf)₂, AuCl₃, or (CF₃CO₂)Ag. A variety of heterocyclic lactones are readily prepared in excellent yields.     

Synthesis of 2-Oxazolines from Ring Opening Isomerization of 3-Amido-2-Phenyl Azetidines

Chiral 2-oxazolines are valuable building blocks and famous ligands for asymmetric catalysis. The most common synthesis involves the reaction of an amino alcohol with a carboxylic acid. In this paper, an efficient synthesis of 2-oxazolines has been achieved via the stereospecific isomerization of 3-amido-2-phenyl azetidines. The reactions were studied in the presence of both Brønsted and Lewis acids, and Cu(OTf)₂ was found to be the most effective.     

Indium‐Catalyzed Synthesis of Keto Esters from Cyclic 1,3‐Diketones and Alcohols and Application to the Synthesis of Seratrodast

Esterification reactions from cyclic 1,3‐diketones and alcohols are carried out in the presence of several Lewis acids. In particular, indium(III) triflate, In(OTf)₃, iron(III) triflate, Fe(OTf)₃, copper(II) triflate, Cu(OTf)₂, and silver(I) triflate, AgOTf, show high catalytic activities. These reactions proceed through the carbon–carbon bond cleavage by a retro‐aldol reaction and were found to be highly regioselective even in the presence of other functional groups. This type of reaction can also be applied to the preparation of the keto esters during the synthesis of seratrodast, which is an antiasthmatic and eicosanoid antagonist.     

Copper-catalyzed arylation of indolin-2,3-ones with arylboronic acids

A convenient and efficient Cu(OTf)₂-catalyzed arylation of indolin-2,3-ones with arylboronic acids using cheap 1,10-phenanthroline hydrate as ligand was developed under air atmosphere, achieving 3-aryl-3-hydroxy-2-oxindoles in good to excellent yields. This catalytic system shows broad functional group tolerance. Moreover, the rigorous exclusion of air/moisture is not required in these transformations.     

Chloromethylated polystyrene supported copper (II) bis–thiazole complex: Preparation,characterization and its application as a heterogeneous catalyst for chemoselective and homoselective synthesis of aryl azides

This work deals the synthesis of aryl azides catalyzed by heterogeneous copper (II) complex of 3,5–bis (2–benzothiazolyl) pyridine, [Cu (II)(BTP)(OTf)₂], immobilized on chloromethylated polystyrene, [Cu (II)(BTP)(OTf)₂]@CMP. The prepared catalyst was characterized by different analytical techniques such as X‐ray diffraction (XRD), thermogravimetric analysis (TGA), field emission scanning electron microscopy (SEM), energy dispersive X–ray spectroscopy (EDX), elemental analysis, and FT‐IR and UV–Vis spectroscopic methods. This catalytic system showed excellent activity in the synthesis of aryl azides by the reaction of aryl halides with sodium azide in the presence of catalytic amounts of [Cu (II)(BTP)(OTf)₂]@CMP. Moreover, this unique catalyst could be recovered easily and reused several times without any considerable loss of its catalytic activity.     

Facile oxidative conversion of hydrazides of carboxylic acids to corresponding acids,esters and amides using copper compounds

Oxidative conversion of hydrazides of carboxylic acids to acids, esters and amides using Cu salts was studied. Acids were obtained in high yields by using a catalytic amount of Cu(OAc)₂ at room temperature by bubbling oxygen. Hydrazides were converted to esters by the treatment with Cu(OR)Cl or Cu(OR)₂ formed in situ from CuCl₂ and sodium alkoxide. Amides were obtained in high yields by the oxidation of hydrazides with CuCl₂ in the presence of amines.     

Conjugate addition of hydroxylamino derivatives to alkylidene malonates in the presence of chiral Lewis acids

The conjugate addition of O-benzylhydroxylamine and N,O-bis(trimethylsilyl)hydroxylamine to alkylidene and arylidene malonates in the presence of Lewis acids affords the corresponding β-hydroxylamino derivatives in good yields. The use of Cu(OTf)₂ in the presence of chiral bisoxazoline ligands opens the possibility of performing this reaction in a catalytic and enantioselective way.     

Copper-catalyzed oxidative coupling of carboxylic acids with formamides for the synthesis of α,β-unsaturated amides

A novel and efficient protocol for the synthesis of α,β-unsaturated amides has been developed using catalytic amount of Cu(OAc)₂ and TBHP as an available oxidant. Oxidative coupling of various unsaturated carboxylic acids with N,N-disubstituted formamides was examined to furnish the desired products in good yields.     

Oxoarylation of ynamides with N-aryl hydroxamic acids

Ynamides are electron-rich alkynes with unique reactivities and act as flexible building blocks in organic synthesis. Therefore, the investigation for transformation of ynamides with exceptional selectivity and efficiency is attractive and interesting. Herein, we report an oxoarylation of ynamides with N-aryl hydroxamic acids. In the presence of catalytic Cu(OTf)₂, both the terminal and internal ynamides could undergo an addition/[3,3] sigmatropic rearrangement cascade with N-aryl hydroxamic acids to achieve oxoarylation, along with providing selective entry to (ortho-amino)arylacetamides and oxindoles. Moreover, deuterium-labelling reaction and gram-scale reaction were conducted to probe the mechanism and showcase the scalability.     

Cu(OTf)2/Et3N-promoted cyclocondensation of activated α-methylene alkenes and nitroolefins: a novel one-pot synthesis of polysubstituted benzenes

A simple and efficient one-pot synthesis of polyfunctionalized benzenes has been developed via cyclocondensation of activated α-methylene alkenes such as vinyl malononitriles and ethyl vinyl cyanoacetates with nitroolefins using Cu(OTf)₂/Et₃N as a novel catalytic system.     

A new and efficient method for the facile synthesis of N-acyl sulfonamides under Lewis acid catalysis

The N-acylation of sulfonamides with carboxylic acid anhydrides in the presence of Lewis acids is described. Several Lewis acids such as BF₃·Et₂O, ZnCl₂, MoCl₅, TiCl₄, B(C₆F₅)₃, Sc(OTf)₃ and I₂ were found to catalyze the reaction efficiently to furnish the N-acylated products in good yields under solvent-free conditions. The reactions of various sulfonamides were studied with different carboxylic acid anhydrides including the less reactive benzoic and pivalic anhydrides, in the presence of 3 mol % ZnCl₂ as the catalyst. Carboxylic acids were also successfully used as acylating agents via the mixed anhydride method.     

Protonation of N-heterocyclic carbene ligand coordinated to copper(I): Coordination mode of imidazolium cation as a function of counterion as determined by solid-state structures

Reactions of (IPr)Cu(X) (X = Cl or trifluoromethanesulfonate, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) complexes with the strong acids HOTf or HCl result in protonation of the C2 carbon of the IPr ligand to form imidazolium cations. Coordination of the imidazolium to the resulting Cu^I system depends upon the identity of the two counterions (chloride or triflate). The copper complexes [(IPrH)Cu(OTf)(μ-OTf)]₂ and [IPrH][CuCl₂] as well as the imidazolium salt [IPrH][OTf] have been characterized by NMR spectroscopy and single crystal X-ray diffraction studies.     

Addition of water to arylidenecyclopropanes: a highly efficient method for the preparation of gem-aryl disubstituted homoallylic alcohols

Arylidenecyclopropanes react with water in the presence of a catalytic amount of Cu(OTf)₂ to afford the corresponding gem-aryl disubstituted homoallylic alcohols in good to excellent yields.     

Cyclization of (2‐Alkenylphenyl)carbonyl Compounds to Polycyclic Arenes Catalyzed by Copper(II) Trifluoromethanesulfonate or Trifluoromethanesulfuric Acid

Various polycyclic arenes, such as naphthalenes, tetrahydroantharacenes, tetrahydrotetracenes, dihydropentacenes, and dihydropentaphenes are prepared from 2‐alkenylphenyl ketones and aldehydes by the catalytic use of copper(II) trifluoromethanesulfonate (Cu(OTf)₂) or trifluoromethanesulfuric acid (TfOH).     

Cu(OTf)2/trisoxazoline catalyzed asymmetric Friedel-Crafts reaction of pyrroles with alkylidene malonates

In the presence of catalytic amount of Cu(OTf)₂/trisoxazoline, an enantioselective Friedel-Crafts reaction of N-methyl pyrrole with alkylidene malonates has been developed and up to 66% ee is achieved.     

A mild,copper-catalysed amide deprotection strategy: use of tert-butyl as a protecting group

Mild methods for the deprotection of organic substrates are of fundamental importance in synthetic chemistry. A new room temperature method using a catalytic amount of Cu(OTf)₂ is reported. This allows use of the tert-butyl group as an amide protecting group. The methodology is also extended to Boc-deprotection.     

Stereocontrol in radical polymerization of acrylic monomers

A clear effect of Lewis acids, such. as scandium trifluoromethanesulfonate [Sc(OTf)₃], on stereocontrol during the radical polymerization of a designed monomer, benzyl α-(methoxymethyl)acrylate was found. This Lewis acid also influenced the stereochemistry in the radical polymerization of methyl methacrylate giving a less syndiotactic and more isotactic polymer, although many Lewis acids were not effective. A catalytic amount of Lewis acids, such as Y(OTf)₃ and Yb(OTf)₃, also significantly enhanced isotactic-specificity during the radical polymerization of acrylamide and its derivatives, N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide. Obvious solvent and temperature effects on tacticity were observed in these polymerizations, and poly(NIPAM) with >80% triad isotactic content has been obtained in the presence of Lewis acids.