Copper(I)-catalyzed regioselective propargylic substitution involving Si-B bond activation

The silicon nucleophile generated by copper(I)-catalyzed Si-B bond activation allows several γ-selective propargylic substitutions. The regioselectivity (γ:α ratio) is strongly dependent on the propargylic leaving group. Chloride is superior to oxygen leaving groups in linear substrates (γ:α > 99:1), and it is only the phosphate group that also shows promising regiocontrol (γ:α = 90:10). That leaving group produces superb γ-selectivity (γ:α > 99:1) in α-branched propargylic systems, and enantioenriched substrates react with excellent central-to-axial chirality transfer.     

Copper(I)-catalyzed hydrophosphination of styrenes

Hydrophosphination of styrenes has been accomplished with metal salts for the first time. (CuOTf)₂·toluene complex is the catalyst of choice, but CuCl can also be used. “In-situ” EPR and NMR studies suggest Cu(I) as the catalytically active metal species, giving exclusively the anti-Markovnikov product. Phosphine oxides or β-ketophosphine oxides can be prepared in one-pot by oxidation with molecular oxygen.     

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(I)-catalyzed amination of halothiophenes with polyamines

Copper(I)-catalyzed hetarylation of a series of polyamines and of 4,7,10-trioxatridecane-1,13-diamine with halothiophenes has been studied with a view to obtaining the corresponding N,N′-dihetaryl derivatives. The target products can be obtained using both 3-iodothiophene in the presence of CuI/L-proline/EtCN or CuI/N,N-dimethylglycine/EtCN as catalytic system and 3-bromothiophene in the system CuI/2-(2-methyl-1-oxopropyl)cyclohexanone/DMF. The latter system is also suitable for the hetarylation of 4,7,10-trioxatridecane-1,13-diamine with 3-iodothiophene. In some cases, N-(thiophen-3-yl) derivatives have also been isolated.     

Lewis base activation of Lewis acids: development of a Lewis base catalyzed selenolactonization

The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric amounts of Lewis bases with "soft" donor atoms (S, Se, P) significant rate enhancements over the background reaction are seen. Preliminary mechanistic investigations have revealed the resting state of the catalyst as well as the significance of a weak Br?nsted acid promoter.     

Pd(II)-catalyzed asymmetric addition of malonates to dihydroisoquinolines

We have developed a highly efficient reaction for catalytic asymmetric addition of malonates to dihydroisoquinolines using chiral Pd(II) complexes. In the reactions, substrates with various substitution patterns were available, and the reactions were complete within several hours (<3 h in most cases) under mild reaction conditions, affording various optically active C1-substituted tetrahydroisoquinoline derivatives (up to 98% yield, up to 97% ee). Furthermore, slow addition of DDQ allowed the in situ generation of the reactive intermediate from the corresponding N-Boc-protected amine, and dehydrogenative addition reaction was successfully demonstrated.     

Copper(I)-catalyzed arylselenylation of aryl bromides and iodides

A new protocol to prepare unsymmetrical diarylselenides using the reaction of aryl bromides and iodides with easily available Bu₃SnSeAr catalyzed by Cu(I) complexes under rather mild conditions and with a very high yield is described.     

Copper(I)-catalyzed boryl substitution of unactivated alkyl halides

Borylation of alkyl halides with diboron proceeded in the presence of a copper(I)/Xantphos catalyst and a stoichiometric amount of K(O-t-Bu) base. The boryl substitution proceeded with normal and secondary alkyl chlorides, bromides, and iodides, but alkyl sulfonates did not react. Menthyl halides afforded the corresponding borylation product with excellent diastereoselectivity, whereas (R)-2-bromo-5-phenylpentane gave a racemic product. Reaction with cyclopropylmethyl bromide resulted in ring-opening products, suggesting the reaction involves a radical pathway.     

Copper(I)-catalyzed carboxylation of aryl- and alkenylboronic esters

The copper(I)-catalyzed carboxylation reaction of aryl- and alkenylboronic esters proceeded smoothly under CO(2) to give the corresponding carboxylic acid in good yield. This reaction showed wide generality with higher functional group tolerance compared to the corresponding Rh(I)-catalyzed reaction.     

Copper(I)-catalyzed highly efficient synthesis of benzoselenazoles and benzotellurazoles

A simple and practical useful synthetic method of 1,3-benzoselenazoles having a heteroatom substituent such as NRR', OR, and SR groups at the 2-position was developed by the copper(I)-catalyzed reaction of 2-bromophenyl (1) or 2-iodophenyl (2) isocyanides with selenium and heteroatom nucleophiles. In addition, the synthesis of 2-amino-1,3-benzotellurazoles is also described.     

Copper(I)-catalyzed amination of aryl halides in liquid ammonia

The amination of aryl halides in liquid ammonia (LNH(3)) is catalyzed by a copper(I) salt/ascorbate system to yield primary aromatic amines in good to excellent yields. The low concentrations of catalyst required and the ease of product isolation suggest that this process has potential industrial applications. Commonly used ligands for analogous metal-catalyzed reactions are not effective. The rate of amination of iodobenzene in liquid ammonia is first order in copper(I) catalyst concentration. The small Hammett ρ = 0.49 for the amination of 4-substituted iodobenzenes in liquid ammonia at 25 °C indicates that the C-I bond is not significantly broken in the transition state structure and that there is a small generation of negative charge in the aryl ring, which is compatible with the oxidative addition of the copper ion being rate limiting.     

Copper(I)-catalyzed enantio- and diastereoselective tandem reductive aldol reaction

[Structure: see text] An efficient method for the enantioselective tandem reductive aldol reaction of methyl acrylate with aldehydes is reported. By using a copper(I) precursor and a proper diphosphane ligand, high reactivities can be reached, with TOF up to 40,000 h-1. Taniaphos-based ligands lead to enantioselectivities of up to 97% in the case of the major syn diastereoisomer.     

Copper(I)-catalyzed cascade dearomatization of 2-substituted tryptophols with arylidonium salts

Copper(I)-catalyzed dearomative arylation and vinylation of 2-substituted tryptophols were realized with a subsequent cyclization reaction. The cascade dearomatization sequence provided versatile furoindoline derivatives with two quaternary carbon centers in good to excellent yields.     

Copper(I)-catalyzed azide-alkyne cycloaddition-assisted polymerization of linear glucose-derived co/polymers

The synthesis of linear and controllable oligomers and polymers using sugar-derived monomers is still highly challenging. Herein, we present a method allowing the linear polymerization of a bifunctional glucose derivative as monomer, which contained an azide group at C1 and a propargyl group at C4 position of the glucose ring. The reaction conditions were optimized by grafting the monomer onto the surface of silica nanoparticles (SiNPs) and at the end-modified polyethylene glycol (PEG). For grafting the surface of SiNPs with the monomer, an azide-bearing chlorosilane linker was synthesized and introduced onto SiNPs surface. The copper(I)-catalyzed azide-alkyne cycloaddition using the glucose-derived monomer led to the growth of linear triazole-linked oligosaccharide-mimics on the surface of SiNPs with a degree of polymerization up to 13 and the formation of cyclic trimers and tetramers in the solution. Furthermore, during polymerization of the monomer at end-modified PEG, various linear diblock-copolymers pseudo-cellulose-block-PEG and triblock-copolymers pseudo-cellulose-block-PEG-block-pseudo-cellulose were obtained. The polymerization reactions expired with nearly complete consumption of the monomer and high yields between 88 and 94% were achieved. Obtained block-copolymers showed amphiphilic properties that helped to fractionate obtained polymers into lower and higher molecular weight fractions with narrow polymer dispersity Đ.     

Copper(I)-catalyzed reaction of acylzirconocene chloride: cross-coupling and conjugate addition

For the purpose of exploring a new reaction of acylzirconocene chloride as an acyl anion donor, Cu(I)-catalyzed cross-coupling and conjugate addition reactions of acylzirconocene chloride were studied. The coupling reaction with allylic or propargylic halides efficiently proceeded to yield β,γ-unsaturated ketone or allenyl ketone derivatives, respectively. The conjugated addition reaction to ,β-enones was carried out in the presence of 2 equiv. of BF₃·OEt₂ giving 1,4-diketone compounds.     

Copper(I)-catalyzed S-arylation of thiols with activated aryl chlorides on water

Copper chloride-catalyzed S-arylation of arenethiols is effected with activated aryl chlorides in neat water by using ethylenediamine as the pair ligand/base. This convenient, environmentally more friendly procedure for the coupling of aryl chlorides allows the arylation between sterically demanding coupling partners.