Copper-Catalyzed Regio Research Articles

Diastereo- and Enantioselective Copper-Catalyzed Decarboxylative Ring-Opening [3 + 2] Annulation of Tertiary Propargylic Carbamates through Regioselective α-Attack of γ-Butenolides.

A copper-catalyzed regio-, diastereo-, and enantioselective decarboxylative ring-opening [3 + 2] annulation of tertiary propargylic carbamates with γ-butenolides for the synthesis of optically active pyrrolidinones has been realized. The reaction proceeded through regioselective α-attack of γ-butenolide and generated highly congested vicinal tertiary and all-carbon quaternary stereocenters in pyrrolidinone scaffolds, featuring high stereoselective induction and broad functional group tolerance. Critical to the successful development of this method was the employment of copper catalysis in concert with a diPh-Pybox ligand.

Ligand-Dependent-Controlled Copper-Catalyzed Regio- and Stereoselective Silaboration of Alkynes.

A copper-catalyzed highly regio- and stereoselective silaboration of alkynes was developed. In this work, direct cis-difunctionalization of alkynes was realized with silaboronate reagent and copper catalyst in aprotic solvents. The regiodivergent silaborations were controlled by tuning the copper catalysts and phosphine ligands used in reactions. This protocol provides an efficient and practical method to synthesize the multisubstituted functionalized alkenes with specific stereoselectivity.

Ligandless Copper‐Catalyzed Carboborylation of Heteroatom‐Substituted Alkynes

AbstractWe have developed an efficient ligand‐free copper‐catalyzed regio‐ and stereoselective carbo‐borylation of heteroatom‐substituted internal alkynes using bis(pinacolato)diboron as boron source and alkyl halides as an electrophile. Both chemical yields and functional group tolerance are excellent. Our method provides an efficient synthesis of tri‐ and tetra‐substituted alkenylboronates which could be further transformed to highly substituted alkenes via subsequent cross‐coupling reactions in one pot.magnified image

Copper-Catalyzed Regio- and Enantio-selective Aminoboration of Alkenes

Copper-Catalyzed Regio- and Enantio-selective Aminoboration of Alkenes

Photoinduced, Copper-Promoted Regio- and Stereoselective Decarboxylative Alkylation of α,β-Unsaturated Acids with Alkyl Iodides

The first example of UV light-induced, copper-catalyzed regio- and stereoselective decarboxylative coupling of α,β-unsaturated acids with alkyl iodides was reported. Under standard conditions, the 1°, 2°, and 3° alkyl iodides proceeded smoothly with the E-selective alkenes obtained in uniformly good yields and high stereoselectivities.

Copper-Catalyzed Regio- and Stereoselective Iodocyanation and Dicyanation of Alkynes with Cyanogen Iodide.

anti-Selective iodocyanation and dicyanation of various internal alkynes has been developed by means of a simple copper catalyst system. The selectivity of the products was switched by tuning the reaction conditions. Mechanistic studies have revealed all of the stepwise pathways including diiodide formation, selective monocyanation, and second cyanation processes.

Asymmetric Synthesis of Borylalkanes via Copper-Catalyzed Enantioselective Hydroallylation.

An efficient synthetic method for preparing enantioenriched secondary borylalkanes has been achieved through a copper-catalyzed regio- and enantioselective hydroallylation of alkenyl boronates and boramides employing hydrosilanes and allylic phosphates. In the presence of a copper catalyst with a chiral Walphos ligand, a range of alkenylboron compounds with an aryl, heteroaryl, or alkyl substituent produced secondary homoallylic alkylboron compounds in good yields and with high enantioselectivities up to 99% ee. The utility of the resulting alkylboronates was demonstrated in an efficient synthesis of (S)-massoialactone.

ChemInform Abstract: Ligand‐Enabled, Copper‐Catalyzed Regio‐ and Stereoselective Synthesis of Trialkylsubstituted Alkenylboronates from Unactivated Internal Alkynes.

We report the first copper-catalyzed regio- and stereoselective borylalkylation of dialkylsubstituted internal alkynes with bis(pinacolato)diboron and alkyl halides. A catalytically generated borylcopper species containing a novel π-accepting N-heterocyclic carbene ligand chemoselectively reacted with unactivated internal alkynes over alkyl halides. The intermediate alkenylcopper species subsequently reacted with alkyl halides, affording the desired products. The copper catalyst differentiated steric demands between the two aliphatic substituents on the C≡C triple bond of the alkyne substrates to exhibit high regioselectivity from a wide range of alkyne/alkyl halide combinations. This method is useful for the straightforward synthesis of trialkylsubstituted alkenylboronates, i.e., versatile precursors for tetrasubstituted alkenes containing three or four different alkylsubstituents, which are difficult to synthesize by other methods.

Copper-Catalyzed Regio- and Stereoselective Aminoboration of Alkenylboronates.

A copper-catalyzed aminoboration of alkenyl dan boronates (dan = 1,8-diaminonaphthyl) with diboron reagents and hydroxylamines has been developed. The reaction proceeds regio- and stereoselectively to form the corresponding β-boryl-α-aminoboronic acid derivatives of potent interest in medicinal chemistry. Additionally, the ligand-controlled syn/anti diastereoselectivity switching and preliminary asymmetric catalysis are also described.

Ligand-Enabled, Copper-Catalyzed Regio- and Stereoselective Synthesis of Trialkylsubstituted Alkenylboronates from Unactivated Internal Alkynes

We report the first copper-catalyzed regio- and stereoselective borylalkylation of dialkylsubstituted internal alkynes with bis(pinacolato)diboron and alkyl halides. A catalytically generated borylcopper species containing a novel π-accepting N-heterocyclic carbene ligand chemoselectively reacted with unactivated internal alkynes over alkyl halides. The intermediate alkenylcopper species subsequently reacted with alkyl halides, affording the desired products. The copper catalyst differentiated steric demands between the two aliphatic substituents on the C≡C triple bond of the alkyne substrates to exhibit high regioselectivity from a wide range of alkyne/alkyl halide combinations. This method is useful for the straightforward synthesis of trialkylsubstituted alkenylboronates, i.e., versatile precursors for tetrasubstituted alkenes containing three or four different alkylsubstituents, which are difficult to synthesize by other methods.

ChemInform Abstract: Asymmetric Synthesis of α‐Aminoboronic Acid Derivatives by Copper‐Catalyzed Enantioselective Hydroamination.

A copper-catalyzed regio- and enantioselective hydroamination of alkenyl dan boronates (dan =1,8-diaminonaphthyl) with hydrosilanes and hydroxylamines proceeds to deliver the chiral α-aminoboronic acids in good yields with high enantiomeric ratios. The key to success is the introduction of an umpolung, electrophilic amination strategy. The copper catalysis can provide an unprecedented catalytic asymmetric approach to alkyl-substituted chiral α-aminoboronic acid derivatives of great potential in the fields of organic synthesis and medicinal chemistry.

Copper-catalyzed regio and diastereoselective three component C–N, C–C and C–O bond forming reaction: oxidative sp3C–H functionalization

Naphthoxazine derivatives were synthesized in good yields in the one-pot reaction of tetrahydroisoquinolines, aromatic benzaldehydes and naphthols employing CuI as a catalyst.

Asymmetric Synthesis of α-Aminoboronic Acid Derivatives by Copper-Catalyzed Enantioselective Hydroamination.

A copper-catalyzed regio- and enantioselective hydroamination of alkenyl dan boronates (dan =1,8-diaminonaphthyl) with hydrosilanes and hydroxylamines proceeds to deliver the chiral α-aminoboronic acids in good yields with high enantiomeric ratios. The key to success is the introduction of an umpolung, electrophilic amination strategy. The copper catalysis can provide an unprecedented catalytic asymmetric approach to alkyl-substituted chiral α-aminoboronic acid derivatives of great potential in the fields of organic synthesis and medicinal chemistry.

ChemInform Abstract: Highly Regio‐ and Stereoselective Synthesis of Boron‐Substituted Enynes via Copper‐Catalyzed Borylation of Conjugated Diynes.

A mild copper-catalyzed regio- and stereoselective monoborylation of conjugated diynes with bis(pinacolato)diboron that affords enynylboronates is reported. The reaction is efficient for different types of conjugated diynes including unsymmetrical diynes and produces enynylboron compounds with high and complementary regioselectivity compared with classical hydrometalation reactions. In particular, the reactions of internal conjugated diynes with a silyl substitution produced highly functionalized enynes with high regio- and stereoselectivity, which can be used in further transformations.

Copper-catalyzed regio- and stereoselective hydroallylation of thioalkynes with allylboronates: a facile and convenient synthesis of 1,4-dienes

A Cu-catalyzed, highly regio-, and stereoselective hydroallylation of thioalkynes has been developed with allylboronates as the allylating reagents, providing stereodefined 1,4-dienyl sulfides in good to excellent yields under very mild reaction conditions. The resulting products can been smoothly converted into skipped dienes by a Ni-catalyzed coupling of C–S bonds with Grignard reagents, thus offering a novel efficient method for the regio- and stereoselective synthesis of 1,4-dienes.

Highly regio- and stereoselective synthesis of boron-substituted enynes via copper-catalyzed borylation of conjugated diynes.

A mild copper-catalyzed regio- and stereoselective monoborylation of conjugated diynes with bis(pinacolato)diboron that affords enynylboronates is reported. The reaction is efficient for different types of conjugated diynes including unsymmetrical diynes and produces enynylboron compounds with high and complementary regioselectivity compared with classical hydrometalation reactions. In particular, the reactions of internal conjugated diynes with a silyl substitution produced highly functionalized enynes with high regio- and stereoselectivity, which can be used in further transformations.

Copper-catalyzed intermolecular and regioselective aminofluorination of styrenes: facile access to β-fluoro-N-protected phenethylamines.

A copper-catalyzed regio- and intermolecular aminofluorination of styrenes has been developed. In this reaction Ph-I=N-Ts and Et3N·3HF act as nitrogen and fluorine sources, respectively. The obtained β-fluoro-N-Ts-phenethylamines can be N-alkylated with subsequent deprotection affording the corresponding β-fluoro-N-alkylated phenethylamines, which are interesting building blocks for compounds acting on neuronal targets.

Copper-catalyzed diamination of unactivated alkenes with hydroxylamines.

A copper-catalyzed regio- and stereoselective diamination of unactivated alkenes has been developed with O-acylhydroxylamines as electrophilic nitrogen sources and oxidants. This method provides the first example of metal-catalyzed alkene diamination for directly installing an electron-rich amino group and extends the diamination scope for the synthesis of diverse 1,2-diamines. It offers a rapid and efficient approach to construct a wide range of 1,2-diamines that are an important structural motif in organic synthesis, medicines, catalysts and ligands.

ChemInform Abstract: Copper‐Catalyzed Regio‐ and Stereoselective O‐Arylation of Enolates.

AbstractThe reaction is very efficient with up to 98% yield, the regio‐ and stereoselectivity are excellent, and only O‐arylation product with Z‐configuration is obtained.

Copper-catalyzed regio- and stereoselective O-arylation of enolates.

Copper-catalyzed O-arylation of enolates with diaryliodonium salts as arylating reagents was realized successfully. As important building blocks, β-aryloxy carbonyl compounds were obtained in up to 98% yield under mild conditions, and complete control of O-arylation and Z-stereoselectivity were achieved. The origin of the selectivity was also discussed.