Enantioselective Palladium(II)‐Catalyzed Intramolecular Aminoarylation of Alkenes by Dual N−H and Aryl C−H Bond Cleavage

An asymmetric palladium‐catalyzed intramolecular oxidative aminoarylation of alkenes has been developed with quinoline–oxazoline chiral ligands and Ag₂CO₃ as the oxidant. Various indolines containing a quaternary stereogenic center were synthesized in high yield with excellent enantioselectivity. Preliminary mechanistic studies suggest that the addition of a catalytic amount of phenylglyoxylic acid significantly accelerates the reaction and slightly enhances the enantioselectivity.     

Rhodium‐Catalyzed Alkene Difunctionalization with Nitrenes

The Rh^II‐catalyzed oxyamination and diamination of alkenes generate 1,2‐amino alcohols and 1,2‐diamines, respectively, in good to excellent yields and with complete regiocontrol. In the case of diamination, the intramolecular reaction provides an efficient method for the preparation of pyrrolidines, and the intermolecular reaction produces vicinal amines with orthogonal protecting groups. These alkene difunctionalizations proceed by aziridination followed by nucleophilic ring opening induced by an Rh‐bound nitrene generated in situ, details of which were uncovered by both experimental and theoretical studies. In particular, DFT calculations show that the nitrogen atom of the putative [Rh]₂=NR metallanitrene intermediate is electrophilic and support an aziridine activation pathway by N ??? N=[Rh]₂ bond formation, in addition to the N ??? [Rh]₂=NR coordination mode.     

Intermolecular Palladium‐Catalyzed Oxidative Fluorocarbonylation of Unactivated Alkenes: Efficient Access to β‐Fluorocarboxylic Esters

A novel palladium‐catalyzed intermolecular oxidative fluorocarbonylation of alkenes has been developed, in which employment of a cooperative process with electrophilic ArIF₂‐meidated alkenes activation and palladium‐catalyzed carbonylation is crucial for the successful catalytic transformation. The current transformation presents the first convenient method to generate β‐fluorinated carboxylic acid derivatives under mild reaction conditions from simple alkenes with excellent regioselectivity.     

Palladium‐Catalyzed Intermolecular Oxidative Coupling Reactions of (Z)‐Enamines with Isocyanides through Selective β‐C(sp2)‐H and/or C=C Bond Cleavage

Herein, two efficient palladium‐catalyzed intermolecular oxidative coupling reactions of (Z)‐enamines with isocyanides via selective β‐C(sp²)‐H and/or C=C bond cleavage have been developed, leading to controllable chemodivergent and stereoselective construction of a wide range of (E)‐β‐carbamoylenamine derivatives containing strong intramolecular hydrogen bonds. Furthermore, possible reaction pathways for these transformations are proposed on the basis of preliminary mechanism studies.     

Palladium(0)‐Catalyzed Directed syn‐1,2‐Carboboration and ‐Silylation: Alkene Scope,Applications in Dearomatization,and Stereocontrol by a Chiral Auxiliary

We report the development of palladium(0)‐catalyzed syn‐selective 1,2‐carboboration and ‐silylation reactions of alkenes containing cleavable directing groups. With B₂pin₂ or PhMe₂Si‐Bpin as nucleophiles and aryl/alkenyl triflates as electrophiles, a broad range of mono‐, di‐, tri‐ and tetrasubstituted alkenes are compatible in these transformations. We further describe a directed dearomative 1,2‐carboboration of electron‐rich heteroarenes by employing this approach. Through use of a removable chiral directing group, we demonstrate the viability of achieving stereoinduction in Heck‐type alkene 1,2‐difunctionalization. This work introduces new avenues to access highly functionalized boronates and silanes with precise regio‐ and stereocontrol.     

Palladium(0)‐Catalyzed Directed syn‐1,2‐Carboboration and ‐Silylation: Alkene Scope,Applications in Dearomatization,and Stereocontrol by a Chiral Auxiliary

We report the development of palladium(0)‐catalyzed syn‐selective 1,2‐carboboration and ‐silylation reactions of alkenes containing cleavable directing groups. With B₂pin₂ or PhMe₂Si‐Bpin as nucleophiles and aryl/alkenyl triflates as electrophiles, a broad range of mono‐, di‐, tri‐ and tetrasubstituted alkenes are compatible in these transformations. We further describe a directed dearomative 1,2‐carboboration of electron‐rich heteroarenes by employing this approach. Through use of a removable chiral directing group, we demonstrate the viability of achieving stereoinduction in Heck‐type alkene 1,2‐difunctionalization. This work introduces new avenues to access highly functionalized boronates and silanes with precise regio‐ and stereocontrol.     

Pd(0) catalyzed intramolecular alkylation: stereoselective synthesis of furan and isoxazoline-2-oxide analogs

New optically pure isoxazoline-2-oxide and furan analogs have been synthesized using Pd(0) catalyzed intramolecular cyclizations. Starting from a meso-diol, optically pure compounds were prepared without utilizing chiral ligands at any stage of the synthesis. The stereochemical outcome of the product (>99% ee) was influenced by desymmetrization catalyzed by Pseudomonas cepacia lipase and the stereoselective nature of the palladium catalyzed transformations.     

Pd/Light‐Accelerated Atom‐Transfer Carbonylation of Alkyl Iodides: Applications in Multicomponent Coupling Processes Leading to Functionalized Carboxylic Acid Derivatives

The atom‐transfer carbonylation reaction of various alkyl iodides thereby leading to carboxylic acid esters was effectively accelerated by the addition of transition‐metal catalysts under photoirradiation conditions. By using a combined Pd/hν reaction system, vicinal C‐functionalization of alkenes was attained in which α‐substituted iodoalkanes, alkenes, carbon monoxide, and alcohols were coupled to give functionalized esters. When alkenyl alcohols were used as acceptor alkenes, three‐component coupling reactions, which were accompanied by intramolecular esterification, proceeded to give lactones. Pd‐dimer complex [Pd₂(CNMe)₆][PF₆]₂, which is known to undergo homolysis under photoirradiation conditions, worked quite well as a catalyst in these three‐ or four‐component coupling reactions. In this metal/radical hybrid system, both Pd radicals and acyl radicals are key players and a stereochemical study confirmed the carbonylation step proceeded through a radical carbonylation mechanism.     

Palladium(II)‐Catalyzed Oxidative Cyclization of Allylic Tosylcarbamates: Scope,Derivatization, and Mechanistic Aspects

A highly selective oxidative palladium(II)‐catalyzed (Wacker‐type) cyclization of readily available allylic tosylcarbamates is reported. This operationally simple catalytic reaction furnishes tosyl‐protected vinyl‐oxazolidinones, common precursors to syn‐1,2‐amino alcohols, in high yield and excellent diasteroselectivity (>20:1). It is demonstrated that both stoichiometric amounts of benzoquinone (BQ) as well as aerobic reoxidation (molecular oxygen) is suitable for this transformation. The title reaction is shown to proceed through overall trans‐amidopalladation of the olefin followed by β‐hydride elimination. This process is scalable and the products are suitable for a range of subsequent transformations such as: kinetic resolution (KR) and oxidative Heck‐, Wacker‐, and metathesis reactions.     

Palladium‐Assisted “Aromatic Metamorphosis” of Dibenzothiophenes into Triphenylenes

Two new palladium‐catalyzed reactions of aromatic sulfur compounds enabled the conversion of dibenzothiophenes into triphenylenes in four steps. This transformation of one aromatic framework into another consists of 1) 4‐chlorobutylation of the dibenzothiophene to form the corresponding sulfonium salt, 2) palladium‐catalyzed arylative ring opening of the sulfonium salt with a sodium tetraarylborate, 3) an intramolecular S_N2 reaction to form a teraryl sulfonium salt, and 4) palladium‐catalyzed intramolecular C? S/C? H coupling through electrophilic palladation. Symmetrical as well as unsymmetrical triphenylenes of interest were synthesized in a tailor‐made fashion in satisfactory overall yields.     

Detection of Palladium(I) in Aerobic Oxidation Catalysis

Palladium(II)‐catalyzed oxidation reactions exhibit broad utility in organic synthesis; however, they often feature high catalyst loading and low turnover numbers relative to non‐oxidative cross‐coupling reactions. Insights into the fate of the Pd catalyst during turnover could help to address this limitation. Herein, we report the identification and characterization of a dimeric Pd^I species in two prototypical Pd‐catalyzed aerobic oxidation reactions: allylic C−H acetoxylation of terminal alkenes and intramolecular aza‐Wacker cyclization. Both reactions employ 4,5‐diazafluoren‐9‐one (DAF) as an ancillary ligand. The dimeric Pd^I complex, [Pd^I(μ‐DAF)(OAc)]₂, which features two bridging DAF ligands and two terminal acetate ligands, has been characterized by several spectroscopic methods, as well as single‐crystal X‐ray crystallography. The origin of this Pd^I complex and its implications for catalytic reactivity are discussed.     

Regioselective 5‐endo‐dig Electrophilic Iodocyclization of Enediynes: A Convenient Route to Iodo‐substituted Indenes and Cyclopenta‐Fused Arenes

An efficient iodine‐mediated regioselective tandem approach for the synthesis of symmetric and asymmetric iodo‐substituted indenes and stereoselective cyclopenta [b]pyridine/thiophenes from easily accessible enediynes that proceeds by in situ formation of an iodonium intermediate followed by a regioselective 5‐endo‐dig cyclization has been described. The intramolecular electrophilic iodocyclization was selectively triggered by a distribution of electronic density along the alkyne bond. Subsequently, the iodo‐substituted indenes were diversified by employing palladium‐catalyzed cross‐coupling reactions and the coupled products were further confirmed by X‐ray crystallographic studies.     

Protecting‐Group‐Free Enantioselective Synthesis of (−)‐Pallavicinin and (+)‐Neopallavicinin

The first enantioselective synthesis of (?)‐pallavicinin and (+)‐neopallavicinin has been achieved in 15 steps. The described synthesis avoids protecting‐group manipulations by synthesis designs predicated on highly chemo‐ and stereoselective transformations. Highlights of the synthesis include a palladium‐catalyzed enantioselective decarboxylative allylation to form the chiral all‐carbon quaternary stereocenter, a palladium‐catalyzed oxidative cyclization to assemble the [3.2.1]‐bicyclic moiety, and an unprecedented LiBHEt₃‐induced fragmentation/protonation of an α‐hydroxy epoxide to form the α‐furan ketone with the desired configuration.     

The syn/anti‐Dichotomy in the Palladium‐Catalyzed Addition of Nucleophiles to Alkenes

In this review the stereochemistry of palladium‐catalyzed addition of nucleophiles to alkenes is discussed, and examples of these reactions in organic synthesis are given. Most of the reactions discussed involve oxygen and nitrogen nucleophiles; the Wacker oxidation of ethylene has been reviewed in detail. An anti‐hydroxypalladation in the Wacker oxidation has strong support from both experimental and computational studies. From the reviewed material it is clear that anti‐addition of oxygen and nitrogen nucleophiles is strongly favored in intermolecular addition to olefin–palladium complexes even if the nucleophile is coordinated to the metal. On the other hand, syn‐addition is common in the case of intramolecular oxy‐ and amidopalladation as a result of the initial coordination of the internal nucleophile to the metal.     

Magnetically‐recoverable Schiff Base Complex of Pd (II) Immobilized on Fe3O4@SiO2 Nanoparticles: An Efficient Catalyst for Mizoroki‐Heck and Suzuki‐Miyaura Coupling Reactions

The activity of Pd(II)‐Schiff base complex molecules grafted on the surface of Fe₃O₄@SiO₂ particles were investigated in the palladium‐catalyzed coupling reactions of aryl halides with alkenes (Mizoroki‐Heck reaction) and phenylboronic acids (Suzuki‐Miyaura reaction) in the absence of phosphorous ligands. This method shows notable advantages such as heterogeneous nature of the catalyst, excellent yields, short reaction times, easy preparation, simplicity of operation, and cleaner reaction profiles. The catalyst can be separated from the reaction mixture by applying a permanent magnet externally and can be reused for several times without significant loss of activity. Also, the amount of palladium leaching has been determined by ICP analysis.     

Palladium‐Catalyzed Oxidative Difunctionalization of Alkenes with α‐Carbonyl Alkyl Bromides Initiated through a Heck‐type Insertion: A Route to Indolin‐2‐ones

The oxidative interception of various σ‐alkyl palladium(II) intermediates with additional reagents for the difunctionalization of alkenes is an important research area. A new palladium‐catalyzed oxidative difunctionalization reaction of alkenes with α‐carbonyl alkyl bromides is described, in which the σ‐alkyl palladium(II) intermediate is generated through a Heck insertion and trapped using an aryl C(sp²)? H bond. This method can be applied to various α‐carbonyl alkyl bromides, including primary, secondary, and tertiary α‐bromoalkyl esters, ketones, and amides.     

Palladium(II)‐Catalyzed Enantioselective Aminotrifluoromethoxylation of Unactivated Alkenes using CsOCF3 as a Trifluoromethoxide Source

Asymmetric Pd^II‐catalyzed intramolecular aminotrifluoromethoxylation of unactivated alkenes using readily accessible and stable CsOCF₃ as a trifluoromethoxide source has been developed, which affords a wide variety of enantiomerically enriched β‐substituted OCF₃‐containing piperidines in good yields. Introducing a sterically bulky group into pyridine‐oxazoline (Pyox) ligands is crucial to increasing both reactivity and enantioselectivity for the reaction. Additionally, the reaction features good functional group compatibility and mild reaction conditions.     

Selective copper(II)-catalyzed aerobic oxidative cleavage of aromatic gem-disubstituted alkenes to carbonyl compounds under neutral and mild conditions

Three copper(II) catalytic systems, CuCl₂·2H₂O, CuCl₂·2H₂O+phenanthroline, and [Cu(μ-Cl)Cl(phen)]₂ were used to cleave alkenes to their corresponding carbonyl compounds under aerobic and neutral conditions. [Cu(μ-Cl)Cl(phen)]₂ shows enhanced selectivity over the other two catalytic systems. The oxidative cleavage reactions were carried out in mixed H₂O/THF solvent system under oxygen (4 atm) at 60°C. The real oxidant is 2-hydroperoxytetrahydrofuran, which is generated in situ in the process through the reaction between THF and oxygen catalyzed by copper(II). The cleavage reactions are selective for aromatic gem-disubstituted alkenes. Aromatic internal alkenes are slow to be oxidized, and both aliphatic terminal and internal alkenes are inert to oxidative cleavage. Free radical scavenger 2,2,6,6, tetramethylpiperidinyl-1-oxyl (TEMPO) deactivates the reaction indicating the involvement of free radical path in the reaction mechanism.     

Palladium(II)‐Catalyzed Aminotrifluoromethoxylation of Alkenes: Mechanistic Insight into the Effect of N‐Protecting Groups

An efficient palladium‐catalyzed regioselective 5‐exo aminotrifluoromethoxylation of alkenes has been established herein, which provides a practical route towards the synthesis of OCF₃‐containing pyrrolidines. tert‐Butyloxycarbonyl (Boc) as an amino protecting group plays a significant role in both the chemo‐ and regioselectivities. In addition, preliminary mechanistic studies reveal that the amino protecting group of substrates and the counter anion of palladium catalyst play critical roles in reaction efficiency presumably due to an isomerization of alkyl‐ Pd(II) intermediates. Moreover, the asymmetric 5‐exo aminotrifluoromethoxylation reaction has also been achieved by introducing a sterically bulky pyridinyl‐oxazoline ligand.     

Palladium‐Catalyzed Oxidative Carbocyclization–Borylation of Enallenes to Cyclobutenes

A highly efficient palladium‐catalyzed oxidative borylation of enallenes was developed for the selective formation of cyclobutene derivatives and fully‐substituted alkenylboron compounds. Cyclobutenes are formed as the exclusive products in MeOH in the presence of H₂O and Et₃N, whereas the use of AcOH leads to alkenylboron compounds. Both reactions showed a broad substrate scope and good tolerance for various functional groups, including carboxylic acid ester, free hydroxy, imide, and alkyl groups. Furthermore, transformations of the borylated products were conducted to show their potential applications.