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/Norbornene‐Mediated CH Activation/ N‐Tosylhydrazone Insertion Reaction: A Route to Highly Functionalized Vinylarenes

A straightforward method for the synthesis of highly functionalized vinylarenes through palladium‐catalyzed, norbornene‐mediated C?H activation/carbene migratory insertion is described. Extension to a one‐pot procedure is also developed. Furthermore, this method can also be used to generate polysubstituted bicyclic molecules. The reaction proceeds under mild conditions to give the products in satisfactory yields using readily available starting materials. This is a Catellani–Lautens reaction that incorporates different types of coupling partners. Additionally, this reaction is the first to demonstrate the possibility of combining Pd‐catalyzed insertion of diazo compounds and Pd‐catalyzed C?H activation.     

Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of NH Imines and Alkynes by CH/NH Activation

Described herein is a manganese‐catalyzed dehydrogenative [4+2] annulation of N? H imines and alkynes, a reaction providing highly atom‐economical access to diverse isoquinolines. This transformation represents the first example of manganese‐catalyzed C? H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H₂ as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition‐metal‐catalyzed C? H activation. Mechanistic studies revealed the five‐membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.     

Palladium‐Catalyzed Intramolecular CH Difluoroalkylation: Synthesis of Substituted 3,3‐Difluoro‐2‐oxindoles

The synthesis of 3,3‐difluoro‐2‐oxindoles through a robust and efficient palladium‐catalyzed C? H difluoroalkylation is described. This process generates a broad range of difluorooxindoles from readily prepared starting materials. The use of BrettPhos as the ligand was crucial for high efficiency. Preliminary mechanistic studies suggest that oxidative addition is the rate‐determining step for this process.     

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.     

Palladium‐Catalyzed CH Fluorosilylation of 2‐Phenylpyridines: Synthesis of Silafluorene Equivalents

Treatment of 2‐phenylpyridines with amino(1,3,2‐dioxaborolan‐2‐yl)diphenylsilane produced fluorosilylated 2‐phenylpyridines in good to excellent yields under palladium catalysis. This reaction is the first example of C? H fluorosilylation. Single‐crystal X‐ray structure analysis revealed a Lewis acid–base interaction between the silicon and nitrogen atoms, and the obtained fluorosilylated products are silafluorene equivalents. The fluorosilylated products showed stronger fluorescence than the corresponding silafluorene derivative.     

Palladium(II)‐Catalyzed Allylic CH Oxidation of Hindered Substrates Featuring Tunable Selectivity Over Extent of Oxidation

The use of Oxone and a palladium(II) catalyst enables the efficient allylic C? H oxidation of sterically hindered α‐quaternary lactams which are unreactive under known conditions for similar transformations. This simple, safe, and effective system for C? H activation allows for unusual tunable selectivity between a two‐electron oxidation to the allylic acetates and a four‐electron oxidation to the corresponding enals, with the dominant product depending on the presence or absence of water. The versatile synthetic utility of both the allylic acetate and enal products accessible through this methodology is also demonstrated.     

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 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.     

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.     

Palladium‐Catalyzed Carbonylative Cyclization of Arenes by CH Bond Activation with DMF as the Carbonyl Source

A novel palladium‐catalyzed CO‐gas‐ and autoclave‐free protocol for the synthesis of 11H‐pyrido[2,1‐b]quinazolin‐11‐ones has been developed. Quinazolinones, which are omnipresent motif in many pharmaceuticals and agrochemicals, were prepared in good yields by C?H bond activation and annulation using DMF as the CO surrogate. A ¹³CO‐labelled DMF control experiment demonstrated that CO gas was released from the carbonyl of DMF with acid as the promotor. The kinetic isotope effect (KIE) value indicated that the C?H activation step may not be involved in the rate‐determining step. This methodology is operationally simple and showed a broad substrate scope with good to excellent yields.     

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 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.     

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.     

Rhodium(III)‐Catalyzed Transannulation of Cyclopropenes with N‐Phenoxyacetamides through CH Activation

An efficient rhodium(III)‐catalyzed synthesis of 2H‐chromene from N‐phenoxyacetamides and cyclopropenes has been developed. The reaction represents the first example of using cyclopropenes as a three‐carbon unit in rhodium(III)‐catalyzed C(sp²)? H activations.     

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.     

Cobalt‐Catalyzed CH Cyanation of Arenes and Heteroarenes

Carboxylate assistance proved to be the key for the success of efficient cobalt(III)‐catalyzed C? H cyanations. Thus, an in situ generated cationic cobalt complex was identified as a versatile catalyst for the site‐selective synthesis of various aromatic and heteroaromatic nitriles with ample substrate scope.     

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 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.     

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.