sp3‐sp2 C‐C Bond Formation via Brønsted Acid Trifluoromethanesulfonic Acid‐Catalyzed Direct Coupling Reaction of Alcohols and Alkenes

A novel and efficient trifluoromethanesulfonic acid‐catalyzed sp³‐sp² C C bond formation reaction through the direct coupling of alcohols with alkenes has been realized under mild conditions. The present protocol provides an attractive approach to a diverse range of polysubstituted olefins in good to excellent yields with high stereo‐ and regioselectivities.     

Copper‐Catalyzed Coupling of Indoles with Dimethylformamide as a Methylenating Reagent

By using N,N‐dimethylformamide (DMF) as a methylenating reagent, the copper‐catalyzed C H activation of indole was demonstrated as an efficient and facile protocol for synthesizing 3,3′‐diindolylmethane (DIM) and its derivatives. The results indicate that copper chloride was the best catalyst among the investigated transition metal salts, which affords an excellent regioselectivity and good yield when tert‐butyl hydroperoxide (TBHP) was used as an oxidant.

     

Nickel‐Catalyzed Coupling of Fluoroarenes and Amines

The combination of bis(cyclooctadiene)nickel [Ni(COD)₂] and 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene hydrochloride (IPr⋅HCl) effectively catalyzes coupling of fluoroarenes with amines in the presence of sodium tert‐butoxide (t‐BuONa). Activated, unactivated and deactivated fluoroarenes as well as fluoropyridines can react with cyclic or acyclic aliphatic amines. The reactions tolerate various functional groups in the fluorides including PhC(O), C(O)NEt₂, CF₃, OMe and vinyl groups.

     

Ruthenium‐Catalyzed Oxidative Homo‐Coupling of 2‐Arylpyridines

A ruthenium‐catalyzed oxidative homo‐coupling reaction of 2‐arylpyridines via C H activation was developed. The reaction could tolerate various functional groups on both the aryl and the pyridyl rings to afford a series of dimerized products with iron(III) chloride (FeCl₃) as a stoichiometric oxidant. A tentative mechanism was proposed for this oxidative C H/C H homo‐coupling.     

Palladium‐Catalyzed Direct Arylations of 1,2,3‐Triazoles with Aryl Chlorides using Conventional Heating

Generally applicable, palladium‐catalyzed direct arylations of 1,2,3‐triazoles with aryl chlorides were accomplished through conventional heating at reaction temperatures of 105–120 °C. Thereby, intra‐ and intermolecular C H bond functionalizations were achieved with a variety of differently substituted chlorides as electrophiles, bearing numerous valuable functional groups.     

Copper‐Catalyzed Three‐Component Coupling of Terminal Alkyne,Dihalomethane and Amine to Propargylic Amines

The direct C H and C halogen activation for C C bond formation is one of the most interesting reactions in organic chemistry. C C bond formation using alkynes as a carbon nucleophilic source is a very useful method in synthesis. Herein, a copper(I) chloride catalyzed three‐component coupling reaction of alkynes, dihalomethanes and amines through C H and C halogen activation to form propargylic amines under mild conditions has been established. The reaction can be conducted in water, in neat or in common organic solvents and it was applicable to both aromatic and aliphatic alkynes with good functional groups tolerance. It represents an excellent example of multi‐component reactions (MCRs), provides an elegant method for the synthesis of propargylic amines which are frequent skeletal components and synthetically versatile key intermediates for the preparation of many nitrogen‐containing biologically active compounds. From the mechanism point of view, this chemistry offers not only a new approach to propargylic amines with new C C and C N bonds formation through C H and C halogen activation, but also provides valuable mechanistic insight into the novel multi‐component reactions.     

Palladium‐Catalyzed and Hybrid Acids‐Assisted Synthesis of [60]Fulleroazepines in One Pot under Mild Conditions: Annulation of N‐Sulfonyl‐2‐aminobiaryls with [60]Fullerene through Sequential C‐H Bond Activation,C‐C and C‐N Bond Formation

An extraordinarily efficient hybrid acids‐assisted, palladium‐catalyzed and chelating‐group‐assisted C H bond activation of N‐sulfonyl‐2‐aminobiaryls and their annulations with [60]fullerene via sequential C C and C N bond formation at room temperature to afford [60]fulleroazepines is demonstrated. The formation of [60]fulleroazepines is highly regioselective and tolerant to both electron‐withdrawing and electron‐donating groups on the aryl moiety and the reaction gives monofunctionalized fullerenes in good yields (up to 54% isolated yield and 92% based on converted C₆₀).     

Ligand‐Free and Heterogeneous Palladium on Carbon‐Catalyzed Hetero‐Suzuki–Miyaura Cross‐Coupling

A ligand‐free and heterogeneous palladium on carbon (Pd/C)‐catalyzed hetero‐Suzuki–Miyaura coupling reaction has been developed. The protocol enables the construction of both heterocyclic‐alicyclic and heterocyclic‐heterocyclic biaryl derivatives in good to excellent yields. Furthermore, Pd/C could be reused. The time‐course study clarified that palladium was leached into the reaction media as the reaction proceeded and then completely deposited on the carbon support.     

Mechanistic Studies on the Palladium‐Catalyzed Direct C‐5 Arylation of Imidazoles: The Fundamental Role of the Azole as a Ligand for Palladium

An in‐depth mechanistic study on the palladium‐catalyzed direct arylation of imidazoles at the C‐5 position is presented. The interactions of triphenylphosphine (PPh₃)‐ligated aryl‐Pd species with 1,2‐dimethyl‐1H‐imidazole (dmim) have been studied in detail. In contrast with previous suggestions, phosphine‐ligated organo‐Pd species are not active and the reaction proceeds through imidazole‐ligated organo‐Pd intermediates. The kinetics of the oxidative addition of aryl halides with dmim‐ligated Pd(0) species have been characterized in a Pd(dba)₂/dmim model system. A thorough study of the equilibria involving novel [ArPd(dmim)₂X] complexes (X=I, OAc) and the unexpected cationic [ArPd(dmim)₃]⁺ is also reported. The ability of these species to effect the C H arylation of dmim at room temperature in the presence of acetate is also demonstrated.

     

Iridium‐Catalyzed Selective Synthesis of 4‐Substituted Benzofurans and Indoles via Directed Cyclodehydration

A directed cyclization‐dehydration cascade of α‐aryloxy ketones and α‐arylamino ketones was efficiently catalyzed by a cationic iridium‐BINAP complex, which afforded various types of 4‐substituted benzofurans and indoles in high yields with complete regioselectivity. The newly developed protocol also enabled the enantioselective preparation of chiral 4‐acetyloxindole using a chiral iridium catalyst.     

One‐Pot Palladium‐Catalyzed Synthesis of Selectively Substituted Phenanthridines by Sequential Aryl‐Aryl and Heck Couplings,Aza‐Michael and Retro‐Mannich Reactions

A catalytic synthesis of selectively substituted phenanthridines is achieved through a reaction sequence involving palladium/norbornene‐catalyzed unsymmetrical aryl‐aryl and Heck couplings followed by aza‐Michael and retro‐Mannich reactions. In spite of the many steps involved the method is very simple and allows the formation of selectively substituted phenanthridines under mild conditions in a straightforward one‐pot reaction starting from readily available aryl iodides and bromides.     

Iron‐Catalyzed Oxidative Mono‐ and Bis‐Phosphonation of N,N‐Dialkylanilines

The dehydrogenative α‐phosphonation of substituted N,N‐dialkylanilines by dialkyl H‐phosphonates was achieved under mild conditions by using environmentally benign iron(II) chloride as catalyst and tert‐butyl hydroperoxide as oxidant. The reaction proceeded in the presence of electron‐donating (methoxy, methyl, benzyl) and electron‐withdrawing ring‐substitutents (bromo, carbonyl, carboxyl, m‐nitro) in moderate to good yields. The X‐ray crystal structure of N‐(5,5‐dimethyl‐2‐oxo‐2λ⁵‐[1,3,2]dioxaphosphinan‐2‐yl‐methyl)‐N‐methyl‐p‐toluidine was determined. Bis‐(4‐(dimethylamino)phenyl)methane and bis‐4,4′‐(dimethylamino)benzophenone underwent bisphosphonation selectively by respective monophosphonation at the remote dimethylamino groups. Furthermore, the use of excess dialkyl H‐phosphonate and oxidant allowed us to functionalize both methyl groups of N(CH₃)₂ in N,N‐dimethyl‐p‐toluidine and N,N‐dimethylaminomesidine, respectively, to obtain α,α′‐bisphosphonatoamines in high yield.     

Copper‐Catalyzed Cascade Reactions of Substituted 4‐Iodopyrazolecarbaldehydes with 1,2‐Phenylenediamines and 2‐Aminophenols

A new approach for the synthesis of novel annulated‐pyrazoles is presented. This protocol includes an intermolecular condensation followed by a copper‐mediated intramolecular C N or C O coupling reaction. The method is applied to a range of substituted 4‐iodopyrazolecarbaldehydes which react with 1,2‐phenylenediamines or 2‐aminophenols to yield substituted 2,4‐ or 1,4‐dihydrobenzo[b]pyrazolo[4,3‐e][1,4]diazepines or substituted‐2H‐ or 1H‐benzo[b]pyrazolo[3,4‐f][1,4]oxazepines, respectively.     

An Unprecedented Rhodium‐Catalyzed Asymmetric Intermolecular Hydroacylation Reaction with Salicylaldehydes

An unprecedented enantio‐ and diastereoselective rhodium‐catalyzed intermolecular hydroacylation reaction of salicylaldehydes with norbornenes is reported in which the corresponding aryl ketones are obtained in high diastereomeric and moderate enantiomeric excesses. It was found that monodentate phosphoramidite ligands gave rise to endo products, while bidentate phosphine ligands catalyzed the reaction to form exo products predominantly.     

Nickel‐Catalyzed Suzuki–Miyaura Coupling of a Tertiary Iodocyclopropane with Wide Boronic Acid Substrate Scope: Coupling Reaction Outcome Depends on Radical Species Stability

We describe a nickel‐catalyzed Suzuki–Miyaura arylation of a tertiary iodocyclopropane with arylboronic acids; this is an efficient and convergent strategy for providing various enantioenriched arylcyclopropanes with a quaternary stereogenic center. This is the first metal‐catalyzed coupling between a tertiary alkyl electrophile and a wide range of aromatics, including heteroaromatics. We found that the outcome of the Ni‐catalyzed coupling with halides as electrophiles was dependent on the stability of the radical species formed during the reaction. The use of tert‐butyl alcohol (t‐BuOH) as the reaction solvent was very effective, because of its stability under the radical‐generating reaction conditions.

     

Iron‐Catalyzed Nitrogen‐Directed Coupling of Arene and Aryl Bromides Mediated by Metallic Magnesium

2‐Arylpyridines, 2‐alkenylpyridine, and aromatic imines can be coupled with aryl bromides in the presence of an iron catalyst, metallic magnesium, a diamine ligand and an organic dihalide oxidant at 0 °C. The use of a 1:1 mixture of tetrahydrofuran and 1,4‐dioxane is essential for this C H bond activation reaction. The reaction has wider scope of the substrate compared with the reaction using a separately prepared Grignard reagent, and proceeds with lower catalyst loading (2.5 mol%).     

Synthesis of Methylene‐Bridge Polyarenes through Palladium‐Catalyzed Activation of Benzylic Carbon‐Hydrogen Bond

In the presence of palladium(II) acetate [Pd(OAc)₂] and an N‐heterocyclic carbene (NHC) ligand, fluorene derivatives can be generated in good to excellent yields from 2‐halo‐2′‐methylbiaryls through the benzylic C H bond activation (14 examples; 81–97% yields). The scope and limitations of this protocol have been examined. A wide range of functional groups, such as alkyl, alkoxy, ester, nitrile, and others, is able to tolerate the reaction conditions herein. The cyclization of an isotope‐labelled biphenyl gave the corresponding product with a primary kinetic isotope effect (k_H/k_D=4.8:1), which indicates that the rate‐determining step of this reaction is the activation of the benzylic C H bond. Moreover, indenofluorenes were also accessed in excellent results from terphenyls (3 examples; 91–92% yields). The cascade reaction of 2,6‐dichloro‐2′‐methylbiphenyl with diphenylacetylene produced 8,9‐diphenyl‐4H‐cyclopenta[def]phenanthrene in 60% yield through the activation of an aryl and a benzylic C H bond.     

Brønsted Acid‐Catalyzed Nucleophilic Substitution of Alcohols

Simple Brønsted acids such as p‐toluenesulfonic acid monohydrate (PTS) or polymer‐bound p‐toluenesulfonic acid efficiently catalyze the direct nucleophilic substitution of the hydroxy group of allylic and benzylic alcohols with a large variety of carbon‐ and heteroatom‐centered nucleophiles. Reaction conditions are mild, the process is conducted under an atmosphere of air without the need for dried solvents, and water is the only side product of the reaction.     

Iron‐Catalyzed Mizoroki–Heck Cross‐Coupling Reaction with Styrenes

In the presence of iron(II) chloride (FeCl₂; 20 mol%) and potassium tert‐butoxide (t‐BuOK; 4 equiv.) in dimethyl sulfoxide (DMSO), aryl and heteroaryl iodides undergo stereoselective Mizoroki–Heck C C cross‐coupling reactions with styrenes at 60 °C giving the corresponding (E)‐alkenes. The best yields are obtained upon adding a ligand (80 mol%) such as proline or picolinic acid. Aryl bromides and pyridinyl bromides are also coupled with styrenes but in lower yields.     

Direct C‐2 Alkylation of Quinoline N‐Oxides with Ethers via Palladium‐Catalyzed Dehydrogenative Cross‐Coupling Reaction

An efficient and concise one‐pot strategy for the direct alkylation of quinoline N‐oxides via palladium‐catalyzed dual C H bonds activation has been developed. This methodology provides quinoline‐containing heterocyclic molecules in moderate to excellent yields.