Polyheterocycles by Palladium(II)‐Catalyzed Oxidative Domino Reactions Involving Direct C?H Functionalization

A novel palladium(II)‐catalyzed oxidative domino reaction sequence of diyne‐enones and substituted indoles to afford polyheterocycles involving direct C H functionalization using air as oxidant has been developed.     

Palladium(II)‐Catalyzed Direct ortho‐C?H Acylation of Anilides by Oxidative Cross‐Coupling with Aldehydes using tert‐Butyl Hydroperoxide as Oxidant

An efficient palladium‐catalyzed C H acylation with aldehydes using tert‐butyl hydroperoxide (TBHP) transforms various anilides into synthetically useful 2‐aminobenzophenone derivatives under mild conditions (40 °C, 3 h). The acylation reaction exhibits excellent regioselectivity and functional group tolerance, and simple aromatic aldehydes, functionalized aliphatic aldehydes and heteroaromatic aldehydes are effective coupling partners. The acylation reaction is probably initiated by a rate‐limiting electrophilic C H cyclopalladation (k_H/k_D=3.6; ρ⁺=−0.74) to form an arylpalladium complex, followed by acyl radical functionalization.     

Rhodium(III)‐Catalyzed Redox‐Neutral C?H Annulation of Arylnitrones and Alkynes for the Synthesis of Indole Derivatives

By using a nitrone as the oxidizing directing group, a mild, practical and efficient rhodium(III)‐catalyzed C H functionalization for the synthesis of indole derivatives has been developed. This reaction obviates the need for an external oxidant and shows good functional group tolerance. The employment of a sterically hindered Mes group on the carbon center of the nitrone is crucial to produce indoles in high yield.

     

Palladium(II)‐Catalyzed Cycloamidination via C(sp2)?H Activation and Isocyanide Insertion

An efficient method for the synthesis of nitrogen heterocycles containing a cyclic amidine moiety has been developed. The process involves palladium‐catalyzed C(sp²) H activation and isocyanide insertion starting with readily accessible ortho‐heteroarene‐substituted aniline derivatives under mild conditions.     

C?H Bond Arylation of Diamondoids Catalyzed by Palladium(II) Acetate

We have developed an effective approach to 1,2‐disubstituted diamondoids by palladium(II) acetate catalyzed functionalization of C H bond. Selective mono‐arylation of the adamantane framework was achieved using picolylamide as a directing group in yields up to 87 %. Kinetic studies in combination with deuterium labeling experiments, competitive experiments and mass spectrometry contribute to the mechanistic understanding of the arylation process of alkanes with number of C H bonds neighboring the directing group. Triflic anhydride promoted cyclization of the directing group generates imidazo[1,5‐a]pyridine derivatives. Acid‐mediated removal of the directing group provides access to 2‐aryl diamondoid carboxylic acids, which are common precursors for the synthesis of various bioactive compounds (drug candidates).

     

One‐Step Synthesis of Substituted Benzofurans from ortho‐ Alkenylphenols via Palladium‐Catalyzed C?H Functionalization

A dehydrogenative oxygenation of C(sp²) H bonds with intramolecular phenolic hydroxy groups has been developed, which provides a straightforward and concise access to structurally diversely benzofurans from ortho‐alkenylphenols. The reaction is catalyzed by palladium on carbon (Pd/C) without any oxidants and sacrificing hydrogen acceptors.

     

Ruthenium(II)‐Catalyzed Oxidative Annulation Reactions of Arylimidazolium Salts via N‐Heterocyclic Carbene‐Directed C?H Activation

An efficient ruthenium(II)‐catalyzed oxidative annulation reaction of various arylimidazolium salts with alkynes via N‐heterocyclic carbene‐directed C H activation to obtain substituted benzo[ij]imidazo[2,1,5‐de]quinolizinium salts is reported. This catalytic reaction proceeds in an excellent regioselective manner when using unsymmetrical alkynes as reactants. The intermediate mono‐annulated products can be obtained by reducing the amount of catalyst. Two catalytically competent N‐heterocyclic carbene‐based cyclometallated ruthenium(II) complexes have been isolated and characterized, which represent the key intermediates in the catalytic cycle. Moreover, most of the products show a strong fluorescent property, indicating their potential for making new light‐emitting materials.

     

Iron‐Catalyzed C?H Fuctionalization of Indoles

An easily available iron catalyst was developed to accomplish the C H functionalization of indoles with α‐aryl‐α‐diazoesters in high yields under mild conditions. The asymmetric C H functionalization of indoles was also realized by using iron complexes of chiral spiro bisoxazolines with up to 78% ee.     

Cadmium(II)‐Catalyzed C?N Cross‐Coupling of Amines with Aryl Iodides

Cadmium diacetate dihydrate [Cd(OAc)₂⋅2 H₂O] in combination with ethylene glycol catalyzes efficiently the C N cross‐coupling of amines with aryl iodides by a benzyne mechanism. Alkyl, aryl and heterocyclic amines are compatible with this system affording the aminated products in high to excellent yield.     

Nickel‐Catalyzed α‐Benzylation of Arylacetonitriles via C?O Activation

Efficient Ni‐catalyzed direct cross‐couplings of benzylic alcohol derivatives with arylacetonitriles via C O activation are described. Various α‐benzylated arylacetonitriles including those with functional groups can be prepared under mild reaction conditions.

     

C?C Bond Formation via C?H Activation and C?N Bond Formation via Oxidative Amination Catalyzed by Palladium‐ Polyoxometalate Nanomaterials Using Dioxygen as the Terminal Oxidant

An efficient heterogeneous palladium‐polyoxometalate catalyst with the formula Pd‐H₆PV₃Mo₉O₄₀/C has been successfully developed for carbon‐carbon (C C) bond formation via carbon‐hydrogen (C H) activation and carbon‐nitrogen (C N) bond formation via oxidative amination using oxygen as the terminal oxidant. The coupling processes are simple, and use relatively mild conditions to form the desired products. In addition, less waste is generated as no additional reagents such as organic/inorganic oxidants are required, and water is the only by‐product generated.     

One‐Pot Synthesis of Symmetrical 2,6‐Diarylpyridines via Palladium/Copper‐Catalyzed Sequential Decarboxylative and Direct C?H Arylation

A palladium(II)/copper oxide (Cu₂O)‐catalyzed one‐pot decarboxylative and direct C H arylation of 2‐picolinic acid with aryl bromides has been developed. Various aryl bromides have been shown to be efficient coupling partners in the presence of dimethyl sulfate, furnishing symmetrical 2,6‐diarylpyridines in moderate to good yields.

     

Mild Palladium‐Catalyzed Oxidative Direct ortho‐C?H Acylation of Anilides under Aqueous Conditions

Palladium‐catalyzed cross‐dehydrogenative coupling between anilides and aromatic aldehydes was achieved under aqueous conditions. A wide variety of the desired benzophenone derivatives was isolated in good to excellent yield. The reaction rate acceleration effect of acid and detergent has been demonstrated. Mechanistic insight has been obtained from quantum chemical calculations.     

Transition Metal‐Catalyzed C?H Activation of Indoles

The last decades have seen a tremendous expanse in the application of C H activation of many different substrate classes, including the invaluable indole scaffold. Following the exciting emergence of C H activation as a multi‐faceted platform for functionalization, a versatile tool box has been developed for the preparation of structurally diverse indoles. This review article discusses recent advances and strategies for transition metal‐catalyzed C H activation of indoles.

     

Synthesis of Isoquinolines via Rhodium(III)‐Catalyzed Dehydrative C?C and C?N Coupling between Oximines and Alkynes

Isoquinolines have been synthesized from the redox‐neutral dehydrative C N and C C cross‐coupling between oximines and alkynes using a catalytic amount of (pentamethylcyclopentadiene)rhodium dichloride dimer {[RhCp*Cl₂]₂} and cesium acetate (CsOAc), a process that involves ortho C H activation of oximines and subsequent functionalization with alkynes. This redox‐neutral catalytic isoquinoline synthesis operates under mild conditions, and is insensitive to moisture or air. A broad scope of coupling partners has been established, and a likely mechanism has been suggested.     

Easy Access to 1‐Amino and 1‐Carbon Substituted Isoquinolines via Cobalt‐Catalyzed C?H/N?O Bond Activation

A green atom‐economical method for the synthesis of highly functionalized 1‐amino and 1‐carbon substituted isoquinolines from the reaction of N′‐hydroxybenzimidamides and aryl ketoximes, respectively, with alkynes via pentamethylcyclopentadienylcobalt(III)‐catalyzed C H/N O bond activation is described. The external oxidant‐free annulation reaction uses the =NOH moiety in N′‐hydroxybenzimidamides or N‐aromatic ketone oximes as the directing group and internal oxidant. This first row transition metal‐catalyzed annulation serves as an efficient alternative for the synthesis of isoquinolines, as water is the only by‐product and expensive noble metals such as rhodium(III), iridium(III), palladium(II), and ruthenium(II) are not required. The reaction proceeds via C H activation, alkyne insertion, reductive elimination, and N O activation.

     

Tetrabutylammonium Iodide‐Catalyzed Phosphorylation of Benzyl C?H Bonds via a Cross‐Dehydrogenative Coupling (CDC) Reaction

Phosphate esters play important roles as biological active principles and synthons in chemistry. An efficient metal‐free approach for the synthesis of phosphate esters through sp³ C H activation is described. By using tetrabutylammonium iodide (Bu₄NI) as a catalyst and tert‐butyl hydroperoxide (TBHP) as an oxidant, various toluene derivatives and phosphorus nucleophiles are tolerated in this transformation, affording the corresponding products in moderate to good yields.

     

Ligand‐Assisted Palladium(II)/(IV) Oxidation for sp3 C?H Fluorination

The direct functionalization of inert sp³ C H bonds is limited to a few bond types. Although the activation of sp³ C H bonds can be accomplished under mild conditions using palladium catalysts, the subsequent functionalization is not trivial due to the high energy required to convert palladium(II) to palladium(IV). We have systematically studied the palladium oxidation using computation‐guided experiments for reactions involving strong chelation control. We find that a mild external ligand could significantly accelerate the oxidation of palladium(II) to palladium(IV) for strong bidentate directing groups. The acceleration is believed to be a result of ligand stabilization of both the palladium(II) and palladium(IV) intermediates.

     

Palladium‐Catalyzed C?H Functionalization of Ferrocenecarboxylic Acid by using 8‐Aminoquinoline as a Removable Directing Group

A mild and efficient palladium‐catalyzed synthetic method for the C H functionalization of N‐(quinolin‐8‐yl)ferrocenecarboxamide has been developed. Various aryl iodides containing I, NO₂, CN, COMe, CO₂Et, and NH functionalities and also alkyl iodides underwent the Pd‐catalyzed intermolecular carbon‐carbon bond forming reaction with ferrocenecarboxamide successfully which led to a diverse array of bis(aryl/alkyl)ferrocenecarboxamides in 34–92% yields. Cross‐coupling of the ferrocenyl C H bond with aryl iodides can also be achieved utilizing an economical Ni catalyst. Additionally, selective monoalkylation of ferrocenecarboxamide was studied using sodium bicarbonate as base and dibenzylphosphoric acid as additive under Pd‐catalyzed reaction conditions. Subsequently, removal of the directing group, 8‐aminoquinoline, from bis(aryl)ferrocenecarboxamides led to bis(aryl)ferrocenes bearing versatile methyl ester and carboxaldehyde functional groups.

     

Rhodium(III)‐Catalyzed Direct C?H Olefination of Arenes with Aliphatic Olefins

A rhodium(III)‐catalyzed direct ortho C H bond olefination of arenes, including but not limited to benzamides, arylpyridines and indoles, with a variety of unactivated aliphatic olefins has been developed. In the presence of catalytic amounts of dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer {[Cp*RhCl₂]₂}, copper(II) acetate monohydrate [Cu(OAc)₂⋅H₂O] and silver hexafluoroantimonate(V) (AgSbF₆), the coupling reaction occurred efficiently to afford the ortho‐olefinated linear products in good to excellent yields with high regio‐ and stereoselectivities, and a range of functional groups in both coupling partners is compatible with the reaction conditions. This protocol relies on the use of directing groups, and the addition of AgSbF₆ as additive is crucial for the catalysis. This new method expands the scope of rhodium(III)‐catalyzed direct C H bond olefination of arenes, and provides a rapid access to useful linear arylation products of unactivated olefins.