Copper‐Catalyzed Amidation of Aryl Iodides in the Presence of Various Chelating Ligands

N,N′‐Dibenzylethylenediamine is presented as a new, efficient, and versatile bidentate ligand suitable for the copper catalyzed formation of the C‐N bond. This bidentate ligand has been demonstrated to facilitate the copper catalyzed cross‐coupling reactions of aryl iodides with amides to afford the desired products in good to excellent yields.     

Copper(I)‐Catalyzed Interrupted Click/Sulfenylation Cascade: One‐Pot Synthesis of Sulfur Cycle Fused 1,2,3‐Triazoles

Herein, we report a practical protocol for the synthesis of sulfur cycle fused 1,2,3‐triazoles through a copper(I)‐catalyzed tandem click/intramolecular sulfenylation reaction. The reaction proceeded via a copper‐catalyzed alkyne azide cycloaddition, followed by interception of the in situ formed cuprate‐triazole intermediate with p‐toluenesulfonothioate. This reaction shows broad substrate scope, complete regioselectivity, and excellent functional group tolerance under mild reaction conditions.     

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.     

Arenesulfonyl iodides: The third universal class of functional initiators for the metal‐catalyzed living radical polymerization of methacrylates and styrenes

The metal‐catalyzed living radical polymerization of methyl methacrylate and styrene initiated with freshly prepared p‐toluenesulfonyl iodide (TsI) and catalyzed with CuX/2,2′‐bipyridine (bpy), where X is Cl, Br, or I, and various self‐regulated copper‐based catalytic systems, such as copper/bpy, copper(I) oxide/bpy, copper(I) sulfide/bpy, copper(I) selenide/bpy, and copper(I) telluride/bpy, is reported. The exchange of C? I into C? Br and C? Cl takes place when the living radical polymerization of methyl methacrylate is catalyzed by copper(I) bromide/bpy and copper(I) chloride/bpy, respectively. Therefore, the use of the TsI initiator facilitates the synthesis, starting from a single initiator, of poly(methyl methacrylate) containing C? I, C? Br, and C? Cl chain ends. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3920–3931, 2005     

Copper‐Catalyzed Aerobic Autoxidation of N‐Hydroxycarbamates Probed by Mass Spectrometry

We present herein a mechanistic investigation by nanoelectrospray ionization mass spectrometry of copper‐catalyzed aerobic oxidative processes involved in the N‐nitrosocarbonyl aldol reaction of N‐hydroxycarbamates. Protonated amine and copper as charge‐tags aided the detection of reaction intermediates, which verified the enamine mechanism together with a competing enol process. Our experimental results reveal that the copper‐catalyzed aerobic oxidation of N‐hydroxycarbamates may proceed through an autoxidation catalytic mechanism in which a CbzNHO^. radical abstracts a hydrogen from the bound N‐hydroxycarbamate to release the nitroso intermediate through a bimolecular hydrogen‐atom transfer. In this process, the chiral diamine also works as a ligand for copper to facilitate the aerobic oxidative step. The dual role of the chiral vicinal diamine as both an aminocatalyst and a bidentate ligand was finally uncovered.     

Regio‐ and Stereospecific 1,3‐Allyl Group Transfer Triggered by a Copper‐Catalyzed Borylation/ortho‐Cyanation Cascade

A copper‐catalyzed borylation/ortho‐cyanation/allyl group transfer cascade was developed. Initiated by an unconventional copper‐catalyzed electrophilic dearomatization, this process features regio‐ and stereospecific 1,3‐transposition of the allyl fragment enabled by an aromatization‐driven Cope rearrangement. This method provides an effective means for the construction of adjacent tertiary and quaternary stereocenters with excellent diastereocontrol.     

Ligand‐Controlled Copper‐Catalyzed Highly Regioselective Difluoromethylation of Allylic Chlorides/Bromides and Propargyl Bromides

Highly regiodivergent copper‐catalyzed allylic/propargylic difluoromethylation reactions by employing different ligands are described. When 5,6‐dimethyl‐1,10‐phenanthroline was used as the ligand, exclusively α‐difluoromethylated products were obtained, while γ‐selective difluoromethylated products were generated when N‐heterocyclic carbene‐SIPr was used as the ligand. Likewise, high α‐ vs. γ‐selectivities were achieved in the presence of similar copper catalysts for the reactions of propargyl bromides. Moreover, a copper‐catalyzed asymmetric allylic difluoromethylation reaction with moderate to good enantioselectivity by the use of chiral ligands was developed.     

Copper‐Catalyzed Electrophilic Etherification of Arylboronic Esters with Isoxazolidines

A copper‐catalyzed electrophilic etherification of arylboronic esters is reported. Isoxazolidines are utilized as easily available and stable [RO]⁺ surrogates to give 1,3‐amino aryl ethers. The O‐selective arylation of isoxazolidines takes place without causing competitive N‐arylation. In contrast to previously reported anionic conditions, our copper‐catalyzed conditions are mild enough to achieve high functional group tolerance. Preliminary mechanistic studies and DFT calculations support that the reaction proceeds via a transmetalation/oxidative addition pathway, followed by a Lewis acid‐promoted reductive elimination to induce the crucial O‐selectivity.     

Copper‐Catalyzed γ‐Selective and Stereospecific Allylic Cross‐Coupling with Secondary Alkylboranes

The scope of the copper‐catalyzed coupling reactions between organoboron compounds and allylic phosphates is expanded significantly by employing triphenylphosphine as a ligand for copper, allowing the use of secondary alkylboron compounds. The reaction proceeds with complete γ‐E‐selectivity and preferential 1,3‐syn stereoselectivity. The reaction of γ‐silicon‐substituted allylic phosphates affords enantioenriched α‐stereogenic allylsilanes.     

Lewis Acid Catalyzed Enantioselective Desymmetrization of Donor–Acceptor meso‐Diaminocyclopropanes

The first Lewis acid catalyzed enantioselective ring‐opening desymmetrization of a donor–acceptor meso‐diaminocyclopropane is reported. The copper(II)‐catalyzed Friedel–Crafts alkylation of indoles and one pyrrole with an unprecedented meso‐diaminocyclopropane delivered enantioenriched, diastereomerically pure urea products, which are structurally related to natural and synthetic bioactive compounds. The development of a new ligand through the investigation of an underexplored subclass of bis(oxazoline) ligands was essential for achieving high enantioselectivities.     

Copper‐Catalyzed Aerobic Oxidative Ring Expansion of Isatins: A Facile Entry to Isoquinolino‐Fused Quinazolinones

A copper‐catalyzed aerobic oxidative ring expansion reaction of isatins with 1,2,3,4‐tetrahydroisoquinoline for the synthesis of tetracyclic quinazolinones has been developed. This reaction is performed smoothly under simple conditions to give the corresponding products in moderate to good yields with good functional group tolerance. The capacity of the resultant 5H‐isoquinolino[1,2‐b]quinazolin‐8(6H)‐one for a range of palladium‐catalyzed directing C—H activation has been further demonstrated, thus giving a broader access to diverse tetracyclic quinazolinones.     

Ligand‐free,copper‐catalyzed,one‐pot,three‐component synthesis of novel 1,2,3‐triazole‐linked indoles in magnetized water

Magnetized water (MW) is used as a green and new solvent‐promoting medium for the one‐pot, three‐component synthesis of novel 1,2,3‐triazole‐linked indoles catalyzed by copper iodide. A broad range of 2‐aryl‐1‐(prop‐2‐ynyl)‐1H‐indole‐3‐carbaldehydes were reacted with alkyl halides and sodium azide via copper‐catalyzed azide–alkyne cycloaddition reactions in MW in the absence of any ligand. This method offers the advantages of short reaction times, green procedure, low cost, simple work‐up, quantitative reaction yields, and no need for any organic solvent.     

Copper‐Catalyzed Regioselective ortho CH Cyanation of Vinylarenes

A copper‐based catalytic technique for the regioselective ortho C? H cyanation of vinylarenes has been developed. This method provides an effective means for the selective functionalization of vinylarene derivatives. A copper‐catalyzed cyanative dearomatization mechanism is proposed to account for the regiochemical course of this reaction.     

Regioselective Conversion of Arenes to N‐aryl‐1,2,3‐triazoles Using CH Borylation

A one‐pot protocol for the synthesis of N‐aryl 1,2,3‐triazoles from arenes by an iridium‐catalyzed C?H borylation/copper catalyzed azidation/click sequence is described. 1 mol % of Cu(OTf)₂ was found to efficiently catalyze both the azidation and the click reaction. The applicability of this method is demonstrated by the late‐stage chemoselective installation of 1,2,3‐triazole moiety into unactivated molecules of pharmaceutical importance.     

Copper‐Catalyzed Arylation of Remote C(sp3)−H Bonds in Carboxamides and Sulfonamides

Reported herein is an unprecedented copper‐catalyzed arylation of remote C(sp³)?H bonds. Stirring a trifluorotoluene solution of either N‐fluorocarboxamides or N‐fluorosulfonamides and arylboronic acids in the presence of a catalytic amount of copper(II) trifluoroacetylacetonate, 2,2′‐bipyridine, and sodium tert‐butoxide afforded the γ‐ and δ‐C(sp³)?H arylated carboxamides and sulfonamides, respectively, in good to high yields. Mechanistic studies indicate that the reaction might proceed through an amidyl radical generation, 1,5‐hydrogen atom transfer (HAT), and copper‐catalyzed cross‐coupling of the resulting carbon radical with arylboronic acids.     

Copper‐Catalyzed Regioselective ortho C?H Cyanation of Vinylarenes

A copper‐based catalytic technique for the regioselective ortho C H cyanation of vinylarenes has been developed. This method provides an effective means for the selective functionalization of vinylarene derivatives. A copper‐catalyzed cyanative dearomatization mechanism is proposed to account for the regiochemical course of this reaction.     

Impact of Substituents Attached to N-Heterocyclic Carbenes on the Catalytic Activity of Copper Complexes in the Reduction of Carbonyl Compounds with Triethoxysilane

By using functionalized imidazolium salts such as 1‐allyl‐3‐alkylimidazolium or 1‐alkyl‐3‐vinylimidazolium salts as carbene ligand precursors, the reduction of aryl ketones with triethoxysilane may be catalyzed by copper salt/imidazolium salt/KO^tBu systems. The functional substituents attached to the N‐heterocyclic carbene (NHC) serve to enhance the catalytic activity. Different copper salts also have an effect on the catalytic activity, with copper(II) acetate monohydrate being superior to copper(I) chloride.     

Synthesis of Spirocyclic C‐Arylglycosides and ‐Ribosides by Ruthenium‐Catalyzed Cycloaddition

Spirocyclic C‐arylglycosides were synthesized from the appropriately protected δ‐gluconolactones. Addition of lithium acetylide followed by glycosylation with 3‐(trimethylsilyl)propargyl alcohol converted the δ‐gluconolactones into silylated diynes. After desilylation, subsequent ruthenium‐catalyzed cycloaddition of the resultant diynes with alkynes or chloroacetonitrile gave spirocyclic C‐arylglycosides in good yields and selectivity. This strategy was also extended to the synthesis of spirocyclic C‐arylribosides from the known γ‐ribonolactone derivative. Moreover, silver‐catalyzed iodination of the sugar diynes followed by ruthenium‐catalyzed cycloaddition with acetylene delivered spirocyclic C‐iodophenylglycosides and ‐ribosides, which were subjected to palladium‐catalyzed C? C bond‐forming reactions and copper‐catalyzed coupling with nitrogen heterocycles to lead to various derivatives.     

Formation of Quaternary Stereogenic Centers by Copper‐Catalyzed Asymmetric Conjugate Addition Reactions of Alkenylaluminums to Trisubstituted Enones

Alkenylaluminums undergo asymmetric copper‐catalyzed conjugate addition (ACA) to β‐substituted enones allowing the formation of stereogenic all‐carbon quaternary centers. Phosphinamine–copper complexes proved to be particularly active and selective compared with phosphoramidite ligands. After extensive optimization, high enantioselectivities (up to 96 % ee) were obtained for the addition of alkenylalanes to β‐substituted enones. Two strategies for the generation of the requisite alkenylaluminums were explored allowing for the introduction of aryl‐ and alkyl‐substituted alkenyl nucleophiles. Moreover, alkyl‐substituted phosphinamine (SimplePhos) ligands were identified for the first time as highly efficient ligands for the Cu‐catalyzed ACA.     

An efficient synthesis of ring‐fused indoles via copper‐catalyzed tandem reaction of N‐(o‐alkynylphenyl)imines

A copper‐catalyzed tandem intramolecular cyclization‐addition reaction of N‐(o‐alkynylphenyl)imines is disclosed. This strategy offers a simple and promising method for accessing ring‐fused indoles. Copyright © 2010 John Wiley & Sons, Ltd.