Palladium‐Catalyzed Decarboxylative ortho‐C(sp2)−H Aroylation of N‐Sulfoximine Benzamides at Room Temperature

A palladium‐catalyzed method for the decarboxylative ortho C?H acylation of N‐sulfoximine benzamides is developed at room temperature. The catalytic method enables easy access to various functionalized 2‐aroylaromatic carboxylic acid derivatives in good isolated yields. Based on our mechanistic studies, a Pd(II)/Pd(IV) catalytic cycle that involves aroyl radical intermediate is proposed for the reaction.     

Cobalt‐Catalyzed Cyclization of N‐Methoxy Benzamides with Alkynes using an Internal Oxidant through C−H/N−O Bond Activation

The cyclization of substituted N‐methoxy benzamides with alkynes in the presence of an easily affordable cobalt complex and NaOAc provides isoquinolone derivatives in good to excellent yields. The cyclization reaction is compatible with a range of functional group‐substituted benzamides, as well as ester‐ and alcohol‐substituted alkynes. The cobalt complex [Co^IIICp*(OR)₂] (R=Me or Ac) serves as an efficient catalyst for the cyclization reaction. Later, isoquinolone derivatives were converted into 1‐chloro and 1‐bromo substituted isoquinoline derivatives in excellent yields in the presence of POCl₃ or PBr₃.     

Palladium‐Catalyzed C−H Alkynylation of Unactivated Alkenes

Palladium‐catalyzed regio‐ and diastereoselective C?H functionalization with bromoalkynes and electronically unbiased olefins is reported. The picolinamide directing group enables the formation of putative 5 and 6‐exo‐metallacycles as intermediates to afford monoalkynylated products in up to 91 % yield in a stereospecific fashion. The systematic study reveals that substrates with a wide range of substituents on the olefin and bromoalkyne coupling partners are tolerated. Chemoselective transformations were demonstrated for the obtained amides, olefins, and alkynes.     

Mild and Efficient Palladium‐Catalyzed Direct Trifluoroethylation of Aromatic Systems by C−H Activation

The introduction of trifluoroalkyl groups into aromatic molecules is an important transformation in the field of organic and medicinal chemistry. However, the direct installation of fluoroalkyl groups onto aromatic molecules still represents a challenging and highly demanding synthetic task. Herein, a simple trifluoroethylation process that relies on the palladium‐catalyzed C?H activation of aromatic compounds is described. With the utilization of a highly active trifluoroethyl(mesityl)iodonium salt, the developed catalytic method enables the first highly efficient and selective trifluoroethylation of aromatic compounds. The robust catalytic procedure provides the desired products in up to 95 % yield at 25 °C in 1.5 to 3 hours and tolerates a broad range of functional groups. The utilization of hypervalent reagents opens new synthetic possibilities for direct alkylations and fluoroalkylations in the field of transition‐metal‐catalyzed C?H activation.     

Palladium‐Catalyzed C−H Silylation through Palladacycles Generated from Aryl Halides

A highly efficient palladium‐catalyzed disilylation reaction of aryl halides through C?H activation has been developed for the first time. The reaction has broad substrate scope. A variety of aryl halides can be disilylated by three types of C?H activation, including C(sp²)?H, C(sp³)?H, and remote C?H activation. In particular, the reactions are also unusually efficient. The yields are essentially quantitative in many cases, even in the presence of less than 1 mol % catalyst and 1 equivalent of the silylating reagent under relatively mild conditions. The disilylated biphenyls can be converted into disiloxane‐bridged biphenyls.     

Palladium‐Catalyzed Carbonylative Annulation of 1‐Hydroxy‐o‐Carborane and Internal Alkynes via Regioselective B‐H Activation

A Pd‐catalyzed three‐component carbonylative‐annulation of 1‐hydroxy‐o‐carborane, internal alkyne and carbon monoxide has been achieved via direct and regioselective cage B?H activation. A class of C,B‐substituted carborano‐coumarin derivatives with potential applications in pharmaceuticals were facilely prepared in moderate to high yields with excellent chemoselectivity and regioselectivity. A plausible reaction mechanism including CO insertion, electrophilic B?H metalation, alkyne insertion and reductive elimination was proposed.     

Regioselective C−H Hydroarylation of Internal Alkynes with Arenecarboxylates: Carboxylates as Deciduous Directing Groups

In the presence of catalytic [Ru(p‐cym)I₂]₂ and the base guanidine carbonate, benzoic acids react with internal alkynes to give the corresponding 2‐vinylbenzoic acids. This alkyne hydroarylation is generally applicable to diversely substituted electron‐rich and electron‐poor benzoic and acrylic acids. Aryl(alkyl)acetylenes react regioselectively with formation of the alkyl‐branched hydroarylation products, and propargylic alcohols are converted into γ‐alkylidene‐δ‐lactones. The hydroarylation can also be conducted decarboxylatively with a different choice of catalyst and reaction conditions. This reaction variant, which does not proceed via intermediate formation of 2‐vinylbenzoic acids, opens up a regioselective, waste‐minimized synthetic entry to vinylarenes.     

Palladium/Norbornene‐Catalyzed C−H Alkylation/Alkyne Insertion/Indole Dearomatization Domino Reaction: Assembly of Spiroindolenine‐Containing Pentacyclic Frameworks

Reported is a highly chemoselective intermolecular annulation of indole‐based biaryls with bromoalkyl alkynes by using palladium/norbornene (Pd/NBE) cooperative catalysis. This reaction is realized through a sequence of Catellani‐type C?H alkylation, alkyne insertion, and indole dearomatization, by forming two C(sp²)?C(sp³) and one C(sp²)?C(sp²) bonds in a single chemical operation, thus providing a diverse range of pentacyclic molecules, containing a spiroindolenine fragment, in good yields with excellent functional‐group tolerance. Preliminary mechanistic studies reveal that C?H bond cleavage is likely involved in the rate‐determining step, and the indole dearomatization might take place through an olefin coordination/insertion and β‐hydride elimination Heck‐type pathway.     

trans‐Carbocarbonation of Internal Alkynes through a Formal anti‐Carbopalladation/C−H Activation Cascade

An intramolecular Pd‐catalyzed cascade reaction is presented that consists of a formal anti‐carbopalladation of a C?C triple bond followed by C?H activation. As a result, oligocyclic ring systems with an embedded tetrasubstituted double bond are formed. The key to success in affording the trans geometry of the emerging double bond are alkyne units with residues that must not undergo β‐hydride elimination (e.g., t‐butyl or silyl groups). Silyl groups proved to be a perfect handle to further convert the tetrasubstituted alkenes. The evaluation of kinetic data with a deuterium‐labeled compound and X‐ray analyses of trapped intermediates provided additional insight into the catalytic cycle.     

Direct Palladium‐Catalyzed β‐Arylation of Lactams

A direct and catalytic method is reported here for β‐arylation of N‐protected lactams with simple aryl iodides. The transformation is enabled by merging soft enolization of lactams, palladium‐catalyzed desaturation, Ar?X bond activation, and aryl conjugate addition. The reaction is operated under mild reaction conditions, is scalable, and is chemoselective. Application of this method to concise syntheses of pharmaceutically relevant compounds is demonstrated.     

Palladium‐Catalyzed Enantioselective C−H Olefination of Diaryl Sulfoxides through Parallel Kinetic Resolution and Desymmetrization

The first example of Pd^II‐catalyzed enantioselective C?H olefination with non‐chiral or racemic sulfoxides as directing groups was developed. A variety of chiral diaryl sulfoxides were synthesized with high enantioselectivity (up to 99 %) through both desymmetrization and parallel kinetic resolution (PKR). This is the first report of Pd^II‐catalyzed enantioselective C(sp²)?H functionalization through PKR, and it represents a novel strategy to construct sulfur chiral centers.     

Rhodium(III)‐Catalyzed Annulation of 2‐Alkenyl Anilides with Alkynes through C−H Activation: Direct Access to 2‐Substituted Indolines

A Rh^III complex featuring an electron‐deficient η⁵‐cyclopentadienyl ligand catalyzed an unusual annulation between alkynes and 2‐alkenyl anilides to form synthetically appealing 2‐substituted indolines. Formally, the process can be viewed as an allylic amination with concomitant hydrocarbonation of the alkyne. Mechanistic experiments indicate that this transformation involves an unusual rhodium migration with a concomitant 1,5‐H shift.     

Ruthenium(II)‐Catalyzed Synthesis of Spirobenzofuranones by a Decarbonylative Annulation Reaction

The first decarbonylative insertion of an alkyne through C?H/C?C activation of six‐membered compounds is reported. The Ru‐catalyzed reaction of 3‐hydroxy‐2‐phenyl‐chromones with alkynes works most efficiently in the presence of the ligand PPh₃ to provide spiro‐indenebenzofuranones. Unlike previously reported metal‐catalyzed decarbonylative annulation reactions, in the present decarbonylative annulation reaction, the annulation occurs before extrusion of carbon monoxide.     

Palladium‐Catalyzed Cross‐Coupling of Alkenyl Carboxylates

Carboxylate esters have many desirable features as electrophiles for catalytic cross‐coupling: they are easy to access, robust during multistep synthesis, and mass‐efficient in coupling reactions. Alkenyl carboxylates, a class of readily prepared non‐aromatic electrophiles, remain difficult to functionalize through cross‐coupling. We demonstrate that Pd catalysis is effective for coupling electron‐deficient alkenyl carboxylates with arylboronic acids in the absence of base or oxidants. Furthermore, these reactions can proceed by two distinct mechanisms for C?O bond activation. A Pd^0/II catalytic cycle is viable when using a Pd⁰ precatalyst, with turnover‐limiting C?O oxidative addition; however, an alternative pathway that involves alkene carbopalladation and β‐carboxyl elimination is proposed for Pd^II precatalysts. This work provides a clear path toward engaging myriad oxygen‐based electrophiles in Pd‐catalyzed cross‐coupling.     

Rhodium(III)‐Catalyzed Three‐Component Reaction of Imines,Alkynes, and Aldehydes through CH Activation

An efficient rhodium(III)‐catalyzed tandem three‐component reaction of imines, alkynes and aldehydes through C?H activation has been developed. High stereo‐ and regioselectivity, as well as good yields were obtained in most cases. The simple and atom‐economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties.     

Palladium‐Catalyzed Trifluoromethylation of (Hetero)Arenes with CF3Br

The CF₃ group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well‐established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl‐substituted (hetero)arenes by palladium‐catalyzed C?H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio‐ and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased.     

Desymmetrization‐Oriented Enantioselective Synthesis of Silicon‐Stereogenic Silanes by Palladium‐Catalyzed C−H Olefinations

A palladium‐catalyzed chelation‐assisted enantioselective C?H olefination of symmetrically diaryl‐substituted tetraorganosilicon derivatives was developed, enabling the generation of nitrogen‐containing silicon‐stereogenic tetraorganosilicon compounds with modest to good yields and good to excellent enantioselectivities (up to 95.5:4.5 e.r.). The Thorpe–Ingold effect exerted by the substituents on silicon was observed to have a profound influence on formation of olefinated products which were further converted into other relevant chiral organosilanes without the loss of enantiomeric purity, thus demonstrating the synthetic utility of the developed enantioselective olefination.     

Diastereoselective [3+2] Annulation of Aromatic/Vinylic Amides with Bicyclic Alkenes through Cobalt‐Catalyzed C−H Activation and Intramolecular Nucleophilic Addition

A highly diastereoselective method for the synthesis of dihydroepoxybenzofluorenone derivatives from aromatic/vinylic amides and bicyclic alkenes is described. This new transformation proceeds through cobalt‐catalyzed C?H activation and intramolecular nucleophilic addition to the amide functional group. Transition‐metal‐catalyzed C?H activation reactions of secondary amides with alkenes usually lead to [4+2] or [4+1] annulation; to the best of our knowledge, this is the first time that a [3+2] cycloaddition is described in this context. The reaction proceeds under mild conditions and tolerates a wide range of functional groups. Mechanistic studies imply that the C?H bond cleavage may be the rate‐limiting step.