Palladium‐Catalyzed Direct Cyclopropylation of Heterocycles

Many 1,3‐azoles and thiophenes are directly cyclopropylated in the presence of a simple palladium catalyst. The relative configuration on the three‐membered rings is retained in the products. Thus, the cyclopropyl–halide bond undergoes concerted oxidative addition to palladium(0) and cyclopropyl radicals are not involved in the productive pathway.     

Palladium‐Catalyzed Cascade Cyclization/Alkynylation Reactions

Palladium‐catalyzed cascade cyclization reactions have witnessed significant improvements in recent years. Among them, palladium‐catalyzed cascade cyclization/alkynylation are especially attractive, which can assemble structurally diverse monocyclic, bicyclic, fused polycyclic, and spirocyclic skeletons with excellent chemoselectivities. In this Minireview, palladium‐catalyzed cascade cyclization/alkynylation have been summarized and discussed in detail with focus on oxypalladation and aminopalladation‐initiated cascade cyclization, intramolecular Heck‐type cascade cyclization, carbocyclizations, cascade cyclizations, and other types of cascade cyclization reactions. Some significant and representative synthetic methodologies and their synthetic applications and reaction mechanisms have also been described.     

Palladium‐Catalyzed Intermolecular Aryliodination of Internal Alkynes

A completely atom economical palladium‐catalyzed addition reaction has been developed to stereoselectively access functionalized tetrasubstituted alkenyl iodides. The palladium catalyst, which bears an electron‐poor bidentate ligand rarely employed in catalysis, is essential to promote the high yielding and chemoselective intermolecular reaction between equimolar amounts of an alkyne and an aryl iodide. This new carbohalogenation reaction is an attractive alternative to traditional synthetic methods, which rely on multistep synthetic sequences and protecting‐group manipulations.     

Palladium‐Catalyzed Intramolecular Alder‐Ene Type Cycloisomerization Reactions

An overview of the recent literature on palladium‐catalyzed intramolecular Alder‐ene (IMAE) reaction of a variety of 1,n‐unsaturated systems is presented. The reaction which was first reported by Trost and Lautens provided an efficient alternative to the thermal or Lewis acid catalyzed cycloisomerizations involving ene‐type reaction. The IMAE cyclization of enynes and dienes has emerged as an important area and found significant applications in building up of complex molecular architectures and in the synthesis of several bioactive natural products. Since highly impactful reviews on this subject have covered the literature till 2015, this article focuses on summarizing the works subsequent to 2015.     

Palladium‐Catalyzed Cascade CH Trifluoroethylation of Aryl Iodides and Heck Reaction: Efficient Synthesis of ortho‐Trifluoroethylstyrenes

A palladium‐catalyzed selective C? H bond trifluoroethylation of aryl iodides has been explored. The reaction allows for the efficient synthesis of a variety of ortho‐trifluoroethyl‐substituted styrenes. Preliminary mechanistic studies indicate that the reaction might involve a key Pd^IV intermediate, which is generated through the rate‐determining oxidative addition of CF₃CH₂I to a palladacycle; the bulky nature of CF₃CH₂I influences the reactivity. Reductive elimination from the Pd^IV complex then leads to the formation of the aryl–CH₂CF₃ bond.     

Palladium‐Catalyzed para‐Selective Alkylation of Electron‐Deficient Arenes

Intermolecular alkylations of electron‐deficient arenes proceed with good para selectivity. Palladium catalysts were used to generate nucleophilic alkyl radicals from alkyl halides, which then directly add onto the arenes. The arene scope and the site of alkylation are opposite to those of classical Friedel–Crafts alkylations, which prefer electron‐rich systems.     

Olefin‐Directed Palladium‐Catalyzed Regio‐ and Stereoselective Hydroboration of Allenes

An olefin‐directed palladium‐catalyzed regio‐ and stereoselective hydroboration of allenes has been developed to afford fully substituted alkenylboron compounds. The reaction showed a broad substrate scope: a number of functionalized allenes, including 2,3‐dienoate, 3,4‐dienoate, 3,4‐dienol, 1,2‐allenylphosphonate, and alkyl‐substituted allenes, could be used in this olefin‐directed allene hydroboration. The olefin unit was proven to be an indispensable element for this transformation.     

Palladium‐Catalyzed Heck‐Type Cross‐Couplings of Unactivated Alkyl Iodides

A palladium‐catalyzed, intermolecular Heck‐type coupling of alkyl iodides and alkenes is described. This process is successful with a variety of primary and secondary unactivated alkyl iodides as reaction partners, including those with hydrogen atoms in the β position. The mild catalytic conditions enable intermolecular C? C bond formations with a diverse set of alkyl iodides and alkenes, including substrates containing base‐ or nucleophile‐sensitive functionality.     

Synthesis of 1‐Difluoroalkylated Isoquinolines via Palladium‐Catalyzed Radical Cascade Difluoroalkylation–Cyclization of Vinyl Isocyanides with Bromodifluoroacetic Derivatives

A general method was developed for the synthesis of 1‐difluoroalkyl isoquinolines via the palladium‐catalyzed radical cascade difluoroalkylation–cyclization of vinyl isocyanides with bromodifluoroacetic derivatives. The difluoroalkylated cyclization products were readily converted to various other valuable gem ‐difluoro‐containing compounds.     

Construction of Quaternary Stereocenters by Palladium‐Catalyzed Carbopalladation‐Initiated Cascade Reactions

The enantioselective synthesis of molecules containing quaternary stereocenters is a field of intense research interest and development. Among the known organic transformations, carbopalladation‐initiated domino transformations constitutes a general method for the construction of compounds containing cyclic or spiro quaternary stereocenters. In this Minireview, recent achievements in palladium‐catalyzed domino Heck/C?H functionalizations and developments in enantioselective carbopalladation‐initiated domino processes are summarized.     

Photocontrolled Iodine‐Mediated Reversible‐Deactivation Radical Polymerization: Solution Polymerization of Methacrylates by Irradiation with NIR LED Light

Herein, near‐infrared (NIR) photocontrolled iodide‐mediated reversible‐deactivation radical polymerization (RDRP) of methacrylates, without an external photocatalyst, was developed using an alkyl iodide (e.g., 2‐iodo‐2‐methylpropionitrile) as the initiator at room temperature. This example is the first use of a series of special solvents containing carbonyl groups (e.g., 1,3‐dimethyl‐2‐imidazolidinone) as both solvent and catalyst for photocontrolled RDRP using long‐wavelength (λ_max=730 nm) irradiation. The polymerization system comprises monomer, alkyl iodide initiator, and solvent. Well‐defined polymers were synthesized with excellent control over the molecular weights and molecular weight distributions (M_w/M_n<1.21). The living features of this system were confirmed by polymerization kinetics, multiple controlled “on‐off” light switching cycles, and chain extension experiments. Importantly, the polymerizations proceeded successfully with various barriers (pork skin and A4 paper), demonstrating the advantage of high‐penetration NIR light.     

Olefin‐Directed Palladium‐Catalyzed Regio‐ and Stereoselective Oxidative Arylation of Allenes

An olefin‐directed palladium‐catalyzed oxidative regio‐ and stereoselective arylation of allenes to afford 1,3,6‐trienes has been established. A number of functionalized allenes, including 2,3‐ and 3,4‐dienoates and 3,4‐dienol derivatives, have been investigated and found to undergo the olefin‐directed allene arylation. The olefin moiety has been proven to be a crucial element for the arylating transformation.     

Synthesis of Cyclooctatetraenes through a Palladium‐Catalyzed Cascade Reaction

Reported is a cascade reaction leading to fully substituted cyclooctatetraenes. This unexpected transformation likely proceeds through a unique 8π electrocyclization reaction of a ene triyne. DFT computations provide the mechanistic basis of this surprizing reaction.     

Assembly of Functionalized 4‐Alkynylisoxazoles by Palladium‐Catalyzed Three‐Component Cascade Cyclization/Alkynylation

A novel N‐heterocyclic carbene (NHC)‐palladium‐catalyzed three‐component cascade cyclization/alkynylation for the synthesis of structurally diverse 4‐alkynylisoxazoles was efficiently developed in ionic liquids. The operational simplicity, without additives, no additional ligands, and 0.5 mol % catalyst loading under air are some of the attractive features of this present protocol.     

Palladium‐Catalyzed Regio‐ and Stereoselective Chlorothiolation of Terminal Alkynes with Sulfenyl Chlorides

Chlorothiolation of terminal alkynes with sulfenyl chlorides yields anti‐adducts without transition‐metal catalysts. In sharp contrast, transition‐metal‐catalyzed chlorothiolation has not been developed to date, possibly because organosulfur compounds can poison catalyst. Herein, the regio‐ and stereoselective palladium‐catalyzed chlorothiolation of terminal alkynes with sulfenyl chlorides is described. syn‐Chlorothiolation offers a complementary synthetic route to chloroalkenyl sulfides. 2‐Chloroalkenyl sulfides can easily be transformed into various sulfur‐containing products, most of which are often found in natural products and pharmaceuticals.     

Palladium‐Catalyzed Oxidative Cycloisomerization of 2‐Cinnamyl‐1,3‐Dicarbonyls: Synthesis of Functionalized 2‐Benzyl Furans

A new palladium‐catalyzed intramolecular oxidative cycloisomerization of readily available starting materials, 2‐cinnamyl‐1,3‐dicarbonyls, has been demonstrated for the creation of structurally diverse 2‐benzyl furans. The cycloisomerization occurs by a regioselective 5‐exo‐trig pathway. The reaction shows a broad substrate scope with good to excellent yields. Furthermore, a one‐pot procedure has been executed by using readily available cinnamyl alcohols and 1,3‐diketones.     

Synthesis of Spiroheterocycles by Palladium‐Catalyzed Domino Cycloisomerization/Cross‐Coupling of α‐Allenols and Baylis–Hillman Acetates

First insights into the reaction between a Baylis–Hillman adduct and an allene moiety have been obtained from the novel domino heterocyclization/cross‐coupling reaction of α‐allenols and Baylis–Hillman acetates, which furnishes [(2,5‐dihydrofuran‐3‐yl)methyl]acrylate derivatives in moderate to good yields.

     

Palladium‐Catalyzed Three‐Component Cascade Reaction: Facial Access to Densely Functionalized Indolizines

A palladium‐catalyzed three‐component cascade reaction of 2‐(2‐enynyl)pyridines with nucleophiles and allyl halides has been developed, enabling the synthesis of densely functionalized indolizines in moderate to good yields. The newly developed methodology offers several practical advantages, including operational simplicity, ready availability of starting materials, and mild reaction conditions.     

Stereoselective Palladium‐Catalyzed C−F Bond Alkynylation of Tetrasubstituted gem‐Difluoroalkenes

A stereoselective Pd(PPh₃)₄‐catalyzed C?F bond alkynylation of tetrasubstituted gem‐difluoroalkenes with terminal alkynes has been developed. This method gives access to a great variety of conjugated monofluoroenynes bearing a tetrasubstituted alkene moiety with well‐defined stereochemistry. Chelation‐assisted oxidative addition of Pd to the C?F bond is proposed to account for the high level of stereocontrol. An X‐ray crystal structure of a key monofluorovinyl Pd^II intermediate has been obtained for the first time as evidence for the proposed mechanism.