Copper-Catalyzed Regio Research Articles

Visible Light-Induced Copper-Catalyzed Regio- and Stereoselective Difluoroalkylthiocyanation of Alkynes.

The first regio- and stereoselective difluoroalkylthiocyanation of alkynes with BrCF2R and KSCN has been disclosed under visible light-induced copper catalysis. The copper complex photosensitizer formed in situ not only promotes the generation of CF2-alkyl radicals but also facilitates the construction of C-SCN bonds, allowing the reaction to proceed smoothly without any additional photocatalysts or radical initiators. Moreover, the challenging internal alkynes can also be transformed to deliver CF2-derived tetrasubstituted olefins with potential applications in agricultural and medicinal chemistry.

Asymmetric Synthesis of SCF3-Substituted Alkylboronates by Copper-Catalyzed Hydroboration of 1-Trifluoromethylthioalkenes.

A synthetic method for preparation of optically active trifluoromethylthio (SCF3) compounds by a copper-catalyzed regio- and enantioselective hydroboration of 1-trifluoromethylthioalkenes with H-Bpin has been developed. The enantioselective hydrocupration of an in situ generated CuH species and subsequent boration reaction generate a chiral SCF3-containing alkylboronate, of which Bpin moiety can be further transformed to deliver various optically active SCF3 molecules. Computational studies suggest that the SCF3 group successfully controls the regioselectivity in the reaction.

Photoinduced Copper-Catalyzed Regio- and Enantioselective Alkynylation of Epoxides

Photoinduced Copper-Catalyzed Regio- and Enantioselective Alkynylation of Epoxides

Copper-Catalyzed Regio- and Stereoselective Hydroarylation of Ynamide.

Presented herein is a copper-catalyzed trans-hydroarylation of ynamides. The reaction showcases the assembly of boronic acids across the carbon-carbon triple bond of ynamides. The reaction proceeds under mild conditions offering a complementary approach for the versatile synthesis of multifunctional (E)-α,β-disubstituted enamides. Moreover, the hydroarylation process is highly regio- and stereoselective. The transformation shows a broad scope (30 examples) and tolerates a wide range of labile functional groups. Control experiments provide substantive evidence supporting the mechanistic cycle and the observed selectivity.

Copper-Catalyzed Regio- and Enantioselective Hydroboration of Difluoroalkyl-Substituted Internal Alkenes.

Catalytic asymmetric hydroboration of fluoroalkyl-substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl-substituted alkenes without fluorine elimination has been a long-standing challenge in this field. Herein, a copper-catalyzed hydroboration of difluoroalkyl-substituted internal alkenes with high levels of regio- and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom-economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.

Copper-Catalyzed Regio- and Stereoselective Formal Hydro(borylmethylsilyl)ation of Internal Alkynes via Alkenyl-to-Alkyl 1,4-Copper Migration.

Catalytic reactions involving 1,n-metal migration from carbon to carbon enable a nonclassical way of constructing organic molecular skeletons, rapidly providing complex molecules from relatively simple precursors. By utilization of this attractive feature, a new and efficient synthesis of alkenylsilylmethylboronates has been developed by formal hydro(borylmethylsilyl)ation of unsymmetric internal alkynes with silylboronates under copper catalysis. The reaction proceeds regioselectively and involves an unprecedented alkenyl-to-alkyl 1,4-copper migration. The reaction mechanism has been investigated by a series of kinetic, NMR, and deuterium-labeling experiments.

Copper-Catalyzed Regio- and Stereoselective Three-Component Coupling of Allenyl Ethers with gem-Dichlorocyclobutenones and B2pin2.

The three-component coupling method for regio- and stereoselective difunctionalization of allenes with allenyl ethers, bis(pinacolato)diboron, and gem-dichlorocyclobutenones as electrophiles was reported, yielding a variety of highly functionalized cyclobutenone products tethering with an alkenylborate fragment. The polysubstituted cyclobutenone products also underwent diverse transformations.

Regio- and Stereoselective Copper-Catalyzed Borylation-Protodeboronation of 1,3-Diynes: Access to (Z)-1,3-Enynes.

A facile method to access (Z)-1,3-enynes is realized via sequential copper-catalyzed regio- and stereoselective borylation-protodeboronation of 1,3-diynes. Pinacolborane, copper(II) acetate, and Xantphos as the ligand efficiently install hydrogen and Bpin in a cis fashion, which is followed by rapid hydrolysis with water. The reaction has wide substrate scope and occurs in a chemoselective fashion.

Copper-Catalyzed Regio- and Stereoselective Hydrothiolation of Allenamides, Enamides, and Ynamides.

We report a simple protocol for the copper-catalyzed hydrothiolation of N-unsaturated precursors, i.e., allenamides, enamides, and ynamides, under mild conditions. This method proceeds with a low loading of a commercially available Cu(CH3CN)4PF6 catalyst and enables the room-temperature transformation of a wide range of aromatic and aliphatic thiols into allylic or vinylic thioethers, 1,3-dithioethers, and thioaminals with good regio- and stereoselectivity.

Ligand-Enabled Copper-Catalyzed Regio- and Stereoselective Allylboration of 1-Trifluoromethylalkenes.

A copper-catalyzed regio- and stereoselective allylboration of 1-trifluoromethylalkenes with bis(pinacolato)diboron (pinB-Bpin) and allylic chlorides has been developed to form functionalized trifluoromethylated products with high diastereoselectivity. The key to success is the judicious choice of Cs2CO3 base and t-Bu-modified dppe-type ligand, which enables the otherwise challenging high catalyst turnover and suppression of the competing defluorination side reaction from an alkylcopper intermediate. The product derivatization of the resulting Bpin moiety can deliver diverse CF3-containing molecules with high stereochemical fidelity.

Copper-Catalyzed Regio- and Stereoselective Sulfonylation of Alkynyl Imines with Sulfonyl Hydrazides: Access to (E)-β-Sulfonyl Enones.

A copper-catalyzed sulfonylation of alkynyl imines with sulfonyl hydrazides has been developed, which exhibited excellent regio- and stereoselectivity and furnished a series of (E)-β-sulfonyl enones in moderate to good yields. Mechanistic studies suggest that this strategy goes through a radical process.

Catalytic Lewis Base Additive Enables Selective Copper-Catalyzed Borylative α-C-H Allylation of Alicyclic Amines.

Functionalized alicyclic amines are important building blocks for the synthesis of bioactive natural compounds and drugs. Existing methods of functionalization are typically limited to the synthesis of protected amines or the use of highly basic organometallic reagents that can compromise functional group tolerance. Here, we report a novel approach that enables the transformation of O-benzoyl hydroxylamines into α-functionalized cyclic secondary amines by means of a copper-catalyzed regio-, stereo-, and chemoselective coupling with allenes and bis(pinacolato)diboron. A key feature of the present transformation is the use of a catalytic Lewis base additive which inhibits the competing C–N bond forming reaction between the catalytically generated boron-substituted allylcopper intermediate with the O-benzoyl hydroxylamine, thus enabling in situ transformation of the latter into an alicyclic imine which undergoes selective C–C bond formation with the allylcopper species.

Copper-Catalyzed Enantioselective Hydrosilylation of Allenes to Access Axially Chiral (Cyclohexylidene)ethyl Silanes.

A novel strategy of copper-catalyzed regio- and enantioselective hydrosilylation of 4-substituted vinylidenecyclohexanes with silanes was developed. In this protocol, various allenes and silanes were used to afford the corresponding (cyclohexylidene)ethyl silanes in moderate to high yields with good enantioselectivities.

Copper-catalyzed regio- and stereo-selective hydrosilylation of terminal allenes to access (E)-allylsilanes

Regioselectivity and stereoselectivity control in hydrosilylation of terminal allenes is challeging. Although the selective synthesis of vinylsilanes, branched allylsilanes or linear (Z)-allylsilanes have been achieved, transition-metal catalyzed hydrosilylation of terminal allenes to access (E)-allylsilane is difficult. Herein, we report a copper-catalyzed selective hydrosilylation reaction of terminal allenes to access (E)-allylsilanes under mild reaction conditions. The reaction shows broad substrate scope, representing an efficient method to prepare trisubstituted (E)-allylsilanes through hydrosilylation reaction of allenes and can also be applied in the synthesis of disubstituted (E)-allylsilanes. The mechanism study reveals that the E-selectivity is kinetically controlled by the catalyst but not by the thermodynamically isomerization of the (Z)-isomer.

Copper-Catalyzed Regio- and Enantioselective Hydroallylation of 1-Trifluoromethylalkenes: Effect of Crown Ether

Copper-Catalyzed Regio- and Enantioselective Hydroallylation of 1-Trifluoromethylalkenes: Effect of Crown Ether

Copper-Catalyzed Synthesis of Tetrasubstituted Alkenes via Regio- and anti-Selective Addition of Silylboronates to Internal Alkynes.

As a new and complementary method for the synthesis of structurally defined tetrasubstituted alkenes, a copper-catalyzed regio- and anti-selective addition of silylboronates to unsymmetric internal alkynes has been developed. A variety of unactivated alkynes can be employed with high selectivity under simple and mild conditions, and the resulting products have been further functionalized by utilizing silyl and boryl groups on the alkene.

Copper-catalyzed regio- and stereoselective fluorocarboalkynylation of alkynes

It is attractive to establish an efficient and practical platform affording functional compounds using readily available feedstocks as starting materials under mild conditions.

Copper-catalyzed regio- and chemoselective selenosulfonylation of 1,6-enynes from sulfur dioxide

An efficient copper-catalyzed multicomponent reaction of 1,6-enynes, diselenides, DABCO·(SO2)2, and cycloketone oxime esters was achieved, providing cyanoalkylsulfonated pyrrolidines in moderate to good yields.

Copper-Catalyzed Regio- and Diastereoselective Additions of Boron-Stabilized Carbanions to Heteroarenium Salts: Synthesis of Azaheterocycles Containing Contiguous Stereocenters

Nucleophilic addition of diborylalkyl reagents to N-alkyl or N-acylpyridinium and related heteroarenium salts has been developed as a key step for the synthesis of nonaromatic nitrogen heterocycles that contain contiguous stereogenic centers. Derivatization of the dihydropyridine products for the synthesis of tetrahydropyridines and piperidines have also been described.

Ligand-free copper-catalyzed regio- and stereoselective 1,1-alkylmonofluoroalkylation of terminal alkynes.

The copper-catalyzed highly regio- and stereoselective 1,1-alkylmonofluoroalkylation of terminal alkynes with α-chloroacetamides and dialkyl 2-fluoromalonate or 2-fluoro-N,N-dialkyl-3-oxobutanamide without an external ligand has been realized. With this novel methodology, (E)-β-monofluoroalkyl-β,γ-unsaturated amides containing quaternary C-F centers can be easily constructed in good to excellent yields.