Palladium‐Catalyzed CH Activation and Intermolecular Annulation with Allenes

A new and efficient Pd^II‐catalyzed intermolecular annulation of N‐benzoylsulfonamide with allenes for the synthesis of 3,4‐dihydroisoquinolin‐1(2H)‐ones is reported. This C?H functionalization is compatible with ambient air and moisture, and it can be applied to terminal or internal allenes with di?erent synthetically attractive functional groups. Control experiments and a kinetic isotope effect study are conducted and a plausible mechanism is proposed.     

Palladium‐Catalyzed CH Activation of N‐Allyl Imines: Regioselective Allylic Alkylations to Deliver Substituted Aza‐1,3‐Dienes

A new mode of activation of an imine via a rare aza‐substituted π‐allyl complex is described. Palladium‐catalyzed C(sp³)? H activation of the N‐allyl imine and the subsequent nucleophilic attack by the α‐alkyl cyanoester produced the 1‐aza‐1,3‐diene as the sole regioisomer. In contrast, nucleophilic attack by the α‐aryl cyanoester exclusively delivered the 2‐aza‐1,3‐diene, which was employed in an inverse‐electron‐demand Diels–Alder reaction for heterobiaryl synthesis.     

Palladium‐Catalyzed Construction of Heteroatom‐Containing π‐Conjugated Systems by Intramolecular Oxidative CH/CH Coupling Reaction

Synthesis of heteroatom‐containing ladder‐type π‐conjugated molecules was successfully achieved via a palladium‐catalyzed intramolecular oxidative C?H/C?H cross‐coupling reaction. This reaction provides a variety of π‐conjugated molecules bearing heteroatoms, such as nitrogen, oxygen, phosphorus, and sulfur atoms, and a carbonyl group. The π‐conjugated molecules were synthesized efficiently, even in gram scale, and larger π‐conjugated molecules were also obtained by a double C?H/C?H cross‐coupling reaction and successive oxidative cycloaromatization.     

Palladium‐Catalyzed Direct CH Functionalization of Benzoquinone

A direct Pd‐catalyzed C? H functionalization of benzoquinone (BQ) can be controlled to give either mono‐ or disubstituted BQ, including the installation of two different groups in a one‐pot procedure. BQ can now be directly functionalized with aryl, heteroaryl, cycloalkyl, and cycloalkene groups and, moreover, the reaction is conducted in environmentally benign water or acetone as solvents.     

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.     

Palladium‐Catalyzed CS Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

The insertion of an aryne into a C? S bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α‐carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2‐quinolinones in high yields under neutral reaction conditions by a C? S activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio‐substituted quinolinone products.     

Palladium‐Catalyzed Zinc‐Amide‐Mediated CH Arylation of Fluoroarenes and Heteroarenes with Aryl Sulfides

C?H arylation of polyfluoroarenes and heteroarenes with aryl sulfides proceeds smoothly with the aid of a palladium–N‐heterocyclic carbene catalyst. A bulky zinc amide, TMPZnCl ? LiCl, plays a key role as an effective base to generate the corresponding arylzinc species in situ. This arylation protocol is practically much easier to perform than our previous method, which necessitates preparation of the arylzinc reagents in advance from the corresponding aryl halides. Aryl sulfides that are prepared through sulfur‐specific reactions, such as S_NAr sulfanylation and extended Pummerer reactions, undergo this direct arylation, offering interesting transformations that are otherwise difficult to achieve with conventional halogen‐based organic synthesis.     

Palladium(0)‐Catalyzed Heck Reaction/CH Activation/Amination Sequence with Diaziridinone: A Facile Approach to Indolines

Indolines are important moieties present in various biologically significant molecules and have attracted considerable attention in synthetic chemistry. This paper describes a Heck reaction/C? H activation/amination sequence for forming indolines using di‐tert‐butyldiaziridinone. The reaction process likely proceeds via a pallada(II)cycle, which is converted into an indoline by oxidative addition to the diaziridinone and two subsequent C? N bond formations.     

Palladium‐Catalyzed Annulation of Diarylamines with Olefins through CH Activation: Direct Access to N‐Arylindoles

A palladium‐catalyzed dehydrogenative coupling between diarylamines and olefins has been discovered for the synthesis of substituted indoles. This intermolecular annulation approach incorporates readily available olefins for the first time and obviates the need of any additional directing group. An ortho palladation, olefin coordination, and β‐migratory insertion sequence has been proposed for the generation of olefinated intermediate, which is found to produce the expected indole moiety.     

Palladium‐Catalyzed Synthesis of Phenanthridine/Benzoxazine‐Fused Quinazolinones by Intramolecular CH Bond Activation

A highly efficient synthesis of phenanthridine/benzoxazine‐fused quinazolinones by ligand‐free palladium‐catalyzed intramolecular C?H bond activation under mild conditions has been developed. The C?C coupling provides the corresponding N‐fused polycyclic heterocycles in good to excellent yields and with wide functional group tolerance.     

Aniline Carbamates: A Versatile and Removable Motif for Palladium‐Catalyzed Directed CH Activation

The aniline carbamate is introduced as a new removable directing group for C?H activation. Its versatility and ability as a directing group are demonstrated by its use in the ortho‐arylation of a wide variety of aniline derivatives under palladium(II) catalysis, with symmetric diaryliodonium salts as aryl donors. The reaction differs from previously reported arylations in its selectivity and its mechanism, as elucidated by kinetic and isotopic experiments. The directing group can also be easily removed under a variety of conditions.     

The Cross‐Dehydrogenative Coupling of CH Bonds: A Versatile Strategy for CC Bond Formations

Over the last decade, substantial research has led to the introduction of an impressive number of efficient procedures which allow the selective construction of C? C bonds by directly connecting two different C? H bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both C? H bonds. This strategy was introduced by the group of Li as cross‐dehydrogenative coupling (CDC) and discloses waste‐minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross‐dehydrogenative C? C formations and provides a comprehensive overview on existing procedures and employed methodologies.     

Mechanistic Study on Rh‐Catalyzed Stereoselective CC/CH Activation of tert‐Cyclobutanols

A mechanistic study was performed on the Rh‐catalyzed stereoselective C?C/C?H activation of tert‐cyclobutanols. The present study corroborated the previous proposal that the reaction occurs by metalation, β‐C elimination, 1,4‐Rh transfer, C?O insertion, and a final catalyst‐regeneration step. The rate‐determining step was found to be the 1,4‐Rh transfer step, whereas the stereoselectivity‐determining step did not correspond to any of the aforementioned steps. It was found that both the thermodynamic stability of the product of the β‐C elimination and the kinetic feasibility of the 1,4‐Rh transfer and C?O insertion steps made important contributions. In other words, three steps (i.e., β‐C elimination, 1,4‐Rh transfer, and C?O insertion) were found to be important in determining the configurations of the two quaternary stereocenters.     

Palladium‐Catalyzed Domino CH/NH Functionalization: An Efficient Approach to Nitrogen‐Bridged Heteroacenes

Palladium‐catalyzed domino C?H/N?H functionalization for the synthesis of novel nitrogen‐bridged thienoacenes and 10H‐benzo[4,5]thieno[3,2‐b]indole derivatives from dihaloarene is reported. This domino sequence consists of initial C?H functionalization of the benzo[b]thiophene moiety, followed by Buchwald–Hartwig coupling. This transformation is also useful for the synthesis of highly π‐extended compounds.     

Copper(I)‐Catalyzed Alkylation of Polyfluoroarenes through Direct CH Bond Functionalization

The copper(I)‐catalyzed alkylation of electron‐deficient polyfluoroarenes with N‐tosylhydrazones and diazo compounds has been developed. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of C(sp²)? C(sp³) bonds with polyfluoroarenes through direct C? H bond functionalization. Mechanistically, copper(I) carbene formation and subsequent migratory insertion are proposed as the key steps in the reaction pathway.     

Palladium‐Catalyzed Dearomative Cyclocarbonylation by CN Bond Activation

A fundamentally novel approach to bioactive quinolizinones is based on the palladium‐catalyzed intramolecular cyclocarbonylation of allylamines. [Pd(Xantphos)I₂], which features a very large bite angle, has been found to facilitate the rapid carbonylation of azaarene‐substituted allylamines into bioactive quinolizinones in good to excellent yields. This transformation represents the first dearomative carbonylation and is proposed to proceed by palladium‐catalyzed C? N bond activation, dearomatization, CO insertion, and a Heck reaction.     

Room‐Temperature ortho‐Alkoxylation and ‐Halogenation of N‐Tosylbenzamides by Using Palladium(II)‐Catalyzed CH Activation

The N‐tosylcarboxamide group can direct the room‐temperature palladium‐catalyzed C?H alkoxylation and halogenation of substituted arenes in a simple and mild procedure. The room‐temperature stoichiometric cyclopalladation of N‐tosylbenzamide was first studied, and the ability of the palladacycle to react with oxidants to form C?X and C?O bonds under mild conditions was demonstrated. The reaction conditions were then adapted to promote room‐temperature ortho‐alkoxylations and ortho‐halogenations of N‐tosylbenzamides using palladium as catalyst. The scope and limitation of both alkoxylations and halogenations was studied and the subsequent functional transformation of the N‐tosylcarboxamide group through nucleophilic additions was evaluated. This methodology offers a simple and mild route to diversely functionalized arenes.     

From Anilines to Isatins: Oxidative Palladium‐Catalyzed Double Carbonylation of CH Bonds

A novel palladium‐catalyzed C? H double carbonylation introduces two adjacent carbonyl groups for the synthesis of isatins from readily available anilines. The reaction proceeds under atmospheric pressure of CO with high regioselectivity and without any additives. Density functional theory investigations indicate that the palladium‐catalyzed double carbonylation catalytic cycle is plausible.     

Silver‐Mediated Oxidative Aliphatic CH Trifluoromethylthiolation

The first example of a practical and direct trifluoromethylthiolation reaction of unactivated aliphatic C? H bonds employs a silver‐based reagent. The reaction is operationally simple, scalable, and proceeds under aqueous conditions in air. Furthermore, its broad scope and good functional‐group compatibility were demonstrated by applying this method to the selective trifluoromethylthiolation of natural products and natural‐product derivatives.