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The divergent synthesis of two indane polyketides of the indidene family, namely (±)‐indidene A (11 steps, 1.7 %) and (+)‐indidene C (13 steps, 1.3 %), is reported. The synthesis of the trans‐configured common indane intermediate was enabled by palladium(0)‐catalyzed methylene C(sp3)−H arylation, which was performed in both racemic and enantioselective (e.r. 99 : 1) modes. Further elaboration of this common intermediate by nickel‐catalyzed dehydrogenative coupling allowed the rapid installation of the aroyl moiety of (±)‐indidene A. In parallel, the biphenyl system of (±)‐ and (+)‐indidene C was constructed by Suzuki–Miyaura coupling. These investigations led us to revise the structures of indidenes B and C. [ABSTRACT FROM AUTHOR]

A PdII‐catalyzed, domino enantioselective desymmetrizative coupling of 7‐azabenzonorbornadienes with alkynylanilines is disclosed herein. This operationally simple transformation generates three covalent bonds and two contiguous stereocenters with excellent enantio‐ and diastereo‐selectivity. The resulting functionalized indole‐dihydronaphthalene‐amine conjugates served as an appealing platform to streamline the diversity‐oriented synthesis (DOS) of other valuable enantioenriched compounds. DFT calculations revealed that the two stabilizing non‐covalent interactions contributed to the observed enantioselectivity. [ABSTRACT FROM AUTHOR]

The active‐site density, intrinsic activity, and durability of Pd−based materials for oxygen reduction reaction (ORR) are critical to their application in industrial energy devices. This work constructs a series of carbon‐based rare‐earth (RE) oxides (Gd2O3, Sm2O3, Eu2O3, and CeO2) by using RE metal–organic frameworks to tune the ORR performance of the Pd sites through the Pd−RExOy interface interaction. Taking Pd−Gd2O3/C as a representative, it is identified that the strong coupling between Pd and Gd2O3 induces the formation of the Pd−O−Gd bridge, which triggers charge redistribution of Pd and Gd2O3. The screened Pd−Gd2O3/C exhibits impressive ORR performance with high onset potential (0.986 VRHE), half‐wave potential (0.877 VRHE), and excellent stability. Similar ORR results are also found for Pd−Sm2O3/C, Pd−Eu2O3/C, and Pd−CeO2/C catalysts. Theoretical analyses reveal that the coupling between Pd and Gd2O3 promotes electron transfer through the Pd−O−Gd bridge, which induces the antibonding‐orbital occupancy of Pd−*OH for the optimization of *OH adsorption in the rate‐determining step of ORR. The pH‐dependent microkinetic modeling shows that Pd−Gd2O3 is close to the theoretical optimal activity for ORR, outperforming Pt under the same conditions. By its ascendancy in ORR, the Pd−Gd2O3/C exhibits superior performance in Zn‐air battery as an air cathode, implying its excellent practicability. [ABSTRACT FROM AUTHOR]

Nanocarbons incorporating non‐hexagonal aromatic rings ‐ such as five‐, seven‐, and eight‐membered rings ‐ have various intriguing physical properties such as curved structures, unique one‐dimensional packing, and promising magnetic, optical, and conductivity properties. Herein, we report an efficient synthetic approach to polycyclic aromatics containing seven‐membered rings via a palladium‐catalyzed intramolecular Ar−H/Ar−Br coupling. In addition to all‐hydrocarbon scaffolds, heteroatom‐embedded heptagon‐containing polyarenes can be efficiently constructed with this method. Rhodium‐ and palladium‐catalyzed sequential six‐ and seven‐membered ring formations also afford complex heptagon‐containing molecular nanocarbons from readily available arylacetylenes and biphenyl boronic acids. Detailed mechanistic analysis by DFT calculations showed the feasibility of seven‐membered ring formation by a concerted metalation‐deprotonation mechanism. This reaction can serve as a template for the synthesis of a wide range of seven‐membered ring‐containing molecular nanocarbons. [ABSTRACT FROM AUTHOR]

Anionic [Pd(0)−X]− ate complex were proposed as key intermediates in Pd‐catalyzed cross‐coupling for decades, but their isolation remained elusive. Herein, a chelating Lewis acidic bis(amidophenolato)silane is introduced as a strong Z‐type ligand which enables the characterization of the first anionic [Pd(0)−X]− ate complex. Intriguingly, these compounds and the neutral L−Pd(0) analogs exhibit a square planar coordination that is highly unusual for a d10 metal. Theoretical methods scrutinize the interaction between the Lewis acidic Si(IV) center and the late transition metal, while reactivity studies shed light on the potential role of anionic additives in oxidative addition reactions. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed skeletal rearrangement of 2‐(2‐allylarylsilyl)aryl triflates has been developed to give highly fused tetrahydrophenanthrosilole derivatives via unprecedented 1,5‐C−Pd/C−Si bond exchange. The reaction pathways can be switched toward 4‐membered ring‐forming C(sp2)−H alkylation by tuning the reaction conditions to give completely different products, fused dihydrodibenzosilepin derivatives, from the same starting materials. The inspection of the reaction conditions revealed the importance of carboxylates in promoting the C−Pd/C−Si bond exchange. [ABSTRACT FROM AUTHOR]

Fluorinated amino acids and related peptides/proteins have been found widespread applications in pharmaceutical and agricultural compounds. However, strategies for introducing a C−F bond into amino acids in an enantioselective manner are still limited and no such asymmetric catalysis strategy has been reported. Herein, we have successfully developed a Pd/Cu/Li ternary system for stereodivergent synthesis of chiral fluorinated amino acids. This method involves a sequential desymmetrization of geminal difluoromethylenes and allylic substitution with amino acid Schiff bases via Pd/Li and Pd/Cu dual activation, respectively. A series of non‐natural amino acids bearing a chiral allylic/benzylic fluorine motif are easily synthesized in high yields with excellent regio‐, diastereo‐, and enantioselectivities (up to >20 : 1 dr and >99 % ee). A density functional theory (DFT) study revealed the F−Cu interaction of the allylic substrate and the Cu catalyst significantly influence the stereoselectivity. [ABSTRACT FROM AUTHOR]

The direct C−H functionalization of 1,2‐benzazaborines, especially asymmetric version, remains a great challenge. Here we report a palladium‐catalyzed enantioselective C−H olefination and allylation reactions of 1,2‐benzazaborines. This asymmetric approach is a kinetic resolution (KR), providing various C−B axially chiral 2‐aryl‐1,2‐benzazaborines and 3‐substituted 2‐aryl‐1,2‐benzazaborines in generally high yields with excellent enantioselectivities (selectivity (S) factor up to 354). The synthetic potential of this reaction is showcased by late‐stage modification of complex molecules, scale‐up reaction, and applications. [ABSTRACT FROM AUTHOR]

A novel and efficient palladium‐catalyzed regioselective and stereodivergent ring‐closing reaction of aminoenynes with aldehydes and boronic acids or hydrosilane is developed. This three‐component reaction allows for the modular synthesis of a series of exocyclic 1,3‐dienes bearing 5‐ to 8‐membered saturated N‐heterocycles. The reactions utilize a simple Pd‐catalyst and work with broad range of aminoenynes, aldehydes and organometallic reagents under mild reaction conditions. The products represent useful intermediates for chemical synthesis due to the versatility of the conjugated diene. Preliminary mechanistic details of the method are also revealed. [ABSTRACT FROM AUTHOR]

Enantioconvergent catalysis enables the conversion of racemic molecules into a single enantiomer in perfect yield and is considered an ideal approach for asymmetric synthesis. Despite remarkable advances in this field, enantioconvergent transformations of inert tertiary C−H bonds remain largely unexplored due to the high bond dissociation energy and the surrounding steric repulsion that pose unparalleled constraints on bond cleavage and formation. Here, we report an enantioconvergent Pd‐catalyzed alkylation of racemic tertiary allylic C−H bonds of α‐alkenes, providing a unique approach to access a broad range of enantioenriched γ,δ‐unsaturated carbonyl compounds featuring quaternary carbon stereocenters. Mechanistic studies reveal that a stereoablative event occurs through the rate‐limiting cleavage of tertiary allylic C−H bonds to generate σ‐allyl‐Pd species, and the achieved E/Z‐selectivity of σ‐allyl‐Pd species effectively regulates the diastereoselectivity via a nucleophile coordination‐enabled SN2′‐allylation pathway. [ABSTRACT FROM AUTHOR]

Transition‐metal‐catalyzed hydroarylation of unsymmetrical internal alkynes remains challenging because of the difficulty in controlling regioselectivity and stereoselectivity. Moreover, the enantioselective hydroarylation of alkynes using organoboron reagents has not been reported. Herein, we report for the first time that palladium compounds can catalyze the hydroarylation of 1‐alkynylindoles with organoborons for the synthesis of chiral C−N atropisomers. A series of rarely reported vinylindole atropisomers was synthesized with excellent regio‐, stereo‐ (Z‐selectivity), and enantioselectivity under mild reaction conditions. The ready availability of organoborons and alkynes and the simplicity, high stereoselectivity, and good functional group tolerance of this catalytic system make it highly attractive. [ABSTRACT FROM AUTHOR]

Methods that can simultaneously install multiple different functional groups to heteroarenes via C−H functionalizations are valuable for complex molecule synthesis, which, however, remain challenging to realize. Here we report the development of vicinal di‐carbo‐functionalization of indoles in a site‐ and regioselective manner, enabled by the palladium/norbornene (Pd/NBE) cooperative catalysis. The reaction is initiated by the Pd(II)‐mediated C3‐metalation and specifically promoted by the C1‐substituted NBEs. The mild, scalable, and robust reaction conditions allow for a good substrate scope and excellent functional group tolerance. The resulting C2‐arylated C3‐alkenylated indoles can be converted to diverse synthetically useful scaffolds. The combined experimental and computational mechanistic study reveals the unique role of the C1‐substituted NBE in accelerating the turnover‐limiting oxidative addition step. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed bissilylation reactions of alkynes with disilane reagents have become one of the most straightforward and efficient protocols to rapidly produce structurally diverse alkenyl silicon derivatives. In these reactions, the utilization of unsymmetrical disilane reagents provided the possibilities for reactivity enhancement as well as the synthetic merits in contrast to symmetrical disilane reagents. However, a major yet challenging objective is achieving precise control over the selectivity including the regioselectivity and the cis/trans‐selectivity. Herein we realized the first divergent bissilylation of alkynoates with our developed air‐stable disilane reagent 8‐(2‐substituted‐1,1,2,2‐tetramethyldisilanyl)quinoline (TMDQ) by means of synergistic Pd/Lewis acid catalytic system. The catalytic system precisely dictates the selectivity, resulting in the divergent synthesis of 1,2‐bissilyl alkenes. The power of these 1,2‐bissilyl alkenes serving as the key synthetic intermediates has been clearly demonstrated by rapid construction of diverse motifs and densely functionalized biologically active compounds. In addition, the origins of the switchable selectivities were well elucidated by experimental and computational studies on the reaction mechanism and were mainly attributed to different ligand steric effects, the use of the specific disilane reagent TMDQ and the different coordination modes of different Lewis acid with alkynoates. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed reductive difluorocarbene transfer reaction that tames difluorocarbene to couple with two electrophiles has been developed, representing a new mode of difluorocarbene transfer reaction. The approach uses low‐cost and bulk industrial chemical chlorodifluoromethane (ClCF2H) as the difluorocarbene precursor. It produces a variety of difluoromethylated (hetero)arenes from widely available aryl halides/triflates and proton sources, featuring high functional group tolerance and synthetic convenience without preparing organometallic reagents. Experimental mechanistic studies reveal that an unexpected Pd0/II catalytic cycle is involved in this reductive reaction, wherein the oxidative addition of palladium(0) difluorocarbene ([Pd0(Ln)]=CF2) with aryl electrophile to generate the key intermediate aryldifluoromethylpalladium [ArCF2Pd(Ln)X], followed by reaction with hydroquinone, is responsible for the reductive difluorocarbene transfer. [ABSTRACT FROM AUTHOR]

Herein, we report a methodology to access isotopically labeled esters and amides from carbonates and carbamates employing an oxygen deletion strategy. This methodology utilizes a decarboxylative carbonylation approach for isotope labeling with near stoichiometric, ex situ generated 12C, or 13C carbon monoxide. This reaction is characterized by its broad scope, functional group tolerance, and high yields, which is showcased with the synthesis of structurally complex molecules. A complementary method that operates by the catalytic in situ generation of CO via the reduction of CO2 liberated during decarboxylation has also been developed as a proof‐of‐concept approach that CO2‐derived compounds can be converted to CO‐containing frameworks. Mechanistic studies provide insight into the catalytic steps which highlight the impact of ligand choice to overcome challenges associated with low‐pressure carbonylation methodologies, along with rational for the development of future methodologies. [ABSTRACT FROM AUTHOR]

Herein, we report a one‐pot method for enantioselective C−H allylation of pyridines at C3 via tandem borane and palladium catalysis. This method involves borane‐catalyzed pyridine hydroboration to generate dihydropyridines, then palladium‐catalyzed enantioselective allylation of the dihydropyridines with allylic esters, and finally air oxidation of the allylated dihydropyridines to afford the products. This method enables the introduction of an allylic group at C3 with excellent regio‐ and enantioselectivities. [ABSTRACT FROM AUTHOR]

Chain walking has been an efficient route to realize the functionalization of inert C(sp3)−H bonds, but this strategy is limited to mono‐olefin migration and functionalization. Herein, we demonstrate the feasibility of tandem directed simultaneous migrations of remote olefins and stereoselective allylation for the first time. The adoption of palladium hydride catalysis and secondary amine morpholine as solvent is critical for achieving high substrate compatibility and stereochemical control with this method. The protocol is also applicable to the functionalization of three vicinal C(sp3)−H bonds and thus construct three continuous stereocenters along a propylidene moiety via a short synthetic process. Preliminary mechanistic experiments corroborated the design of simultaneous walking of remote dienes. [ABSTRACT FROM AUTHOR]

We describe a catalytic cascade sequence involving directed C(sp3)−H activation followed by β‐heteroatom elimination to generate a PdII(π‐alkene) intermediate that then undergoes redox‐neutral annulation with an ambiphilic aryl halide to access 5‐ and 6‐membered (hetero)cycles. Various alkyl C(sp3)−oxygen, nitrogen, and sulfur bonds can be selectively activated, and the annulation proceeds with high diastereoselectivity. The method enables modification of amino acids with good retention of enantiomeric excess, as well as σ‐bond ring‐opening/ring‐closing transfiguration of low‐strain heterocycles. Despite its mechanistic complexity, the method employs simple conditions and is operationally straightforward to perform. [ABSTRACT FROM AUTHOR]

This paper describes a new method for the transannular functionalization of the γ‐C−H bonds in alicyclic amines to install C(sp3)−halogen, oxygen, nitrogen, boron, and sulfur bonds. The key challenge for this transformation is controlling the relative rate of Cγ−H versus Cα−H functionalization. We demonstrate that this selectivity can be achieved by pre‐complexation of the substrate with Pd prior to the addition of oxidant. This approach enables the use of diverse oxidants that ultimately install various heteroatom functional groups at the γ‐position with high site‐ and diastereoselectivity. [ABSTRACT FROM AUTHOR]

The catalytic enantioselective synthesis of α‐chiral alkenes and alkynes represents a powerful strategy for rapid generation of molecular complexity. Herein, we report a transient directing group (TDG) strategy to facilitate site‐selective palladium‐catalyzed reductive Heck‐type hydroalkenylation and hydroalkynylation of alkenylaldehyes using alkenyl and alkynyl bromides, respectively, allowing for construction of a stereocenter at the δ‐position with respect to the aldehyde. Computational studies reveal the dual beneficial roles of rigid TDGs, such as L‐tert‐leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion with a variety of migrating groups. [ABSTRACT FROM AUTHOR]

The insertion of palladium(II) into di‐p‐pyrirubyrin results in mutually convertible bimetallic complexes. Post‐synthetic functionalization of one of them yielded bispalladium(II) dioxo‐di‐p‐pyrirubyrin and, after demetallation, dioxo‐di‐p‐pyrirubyrin, introducing for the first time the α,β′‐pyridin‐2‐one unit into the macrocyclic frame. Bispalladium(II) di‐p‐pyrirubyrin 6, bispalladium(II) dioxo‐di‐p‐pyrirubyrin 9, and dioxo‐di‐p‐pyrirubyrin 10 absorb and emit light around 1000 nm and are characterized by high photostability. Thus, they are promising candidates for near‐infrared photoacoustic dyes, ideally targeting (9) the wavelength of Yb‐based fiber lasers. The incorporation of an α,β′‐pyridine moiety into expanded porphyrins opens a highly interesting area of research due to the attractive optical and coordination properties of the resulting molecules. [ABSTRACT FROM AUTHOR]

1,3‐Difunctionalized cyclobutanes are an emerging scaffold in medicinal chemistry that can confer beneficial pharmacological properties to small‐molecule drug candidates. However, the diastereocontrolled synthesis of these compounds typically requires complicated synthetic routes, indicating a need for novel methods. Here, we report a sequential C−H/C−C functionalization strategy for the stereospecific synthesis of cis‐γ‐functionalized cyclobutyl ketones from readily available cyclobutyl aryl ketones. Specifically, a bicyclo[1.1.1]pentan‐2‐ol intermediate is generated from the parent cyclobutyl ketone via an optimized Norrish‐Yang procedure. This intermediate then undergoes a ligand‐enabled, palladium‐catalyzed C−C cleavage/functionalization to produce valuable cis‐γ‐(hetero)arylated, alkenylated, and alkynylated cyclobutyl aryl ketones, the benzoyl moiety of which can subsequently be converted to a wide range of functional groups including amides and esters. [ABSTRACT FROM AUTHOR]

Highly oxygenated cardiotonic steroids, such as ouabain, possess a wide spectrum of biological functions and remain significant synthetic challenges. Herein, we have applied an unsaturation‐functionalization strategy and developed a synthetic method in addressing the C19‐hydroxylation issue for efficient synthesis of polyhydroxylated steroids. An effective asymmetric dearomative cyclization allowed the construction of the C19‐hydroxy unsaturated steroidal skeleton in only four steps from the Hajos‐Parrish ketone ketal 7. The synthetic sequence featured C3−OH‐directed hydrogenation/epoxidation, m‐CPBA‐triggered epoxidation/SN2′ nucleophilic substitution, Birch reduction of an enone, and regioselective LiAlH4 reduction to furnish the polyhydroxy functionalities on the steroid skeleton with high stereochemical control and efficiency. This approach ultimately enabled the total synthesis of 19‐hydroxysarmentogenin and ouabagenin in 18 and 19 steps, respectively, overall. The synthesis of these polyhydroxylated steroids offers synthetic versatility and practicality in the search for new therapeutic agents. [ABSTRACT FROM AUTHOR]

A novel, selective and high‐yielding palladium‐catalyzed carbonylative arylation of a variety of weakly acidic (pKa 25–35 in DMSO) benzylic and heterobenzylic C(sp3)−H bonds with aryl bromides has been achieved. This system is applicable to a range of pro‐nucleophiles for access to sterically and electronically diverse α‐aryl or α,α‐diaryl ketones, which are ubiquitous substructures in biologically active compounds. The Josiphos SL‐J001‐1‐based palladium catalyst was identified as the most efficient and selective, enabling carbonylative arylation with aryl bromides under 1 atm CO to provide the ketone products without the formation of direct coupling byproducts. Additionally, (Josiphos)Pd(CO)2 was identified as the catalyst resting state. A kinetic study suggests that the oxidative addition of aryl bromides is the turnover‐limiting step. Key catalytic intermediates were also isolated. [ABSTRACT FROM AUTHOR]

The catalytic asymmetric construction of N−N atropisomeric biaryls remains a formidable challenge. Studies of them lag far behind studies of the more classical carbon‐carbon biaryl atropisomers, hampering meaningful development. Herein, the first palladium‐catalyzed enantioselective C−H activation of pyrroles for the synthesis of N−N atropisomers is presented. Structurally diverse indole‐pyrrole atropisomers possessing a chiral N−N axis were produced with good yields and high enantioselectivities by alkenylation, alkynylation, allylation, or arylation reactions. Furthermore, the kinetic resolution of trisubstituted N−N heterobiaryls with more sterically demanding substituents was also achieved. Importantly, this versatile C−H functionalization strategy enables iterative functionalization of pyrroles with exquisite selectivity, expediting the formation of valuable, complex, N−N atropisomers. [ABSTRACT FROM AUTHOR]

A method for the asymmetric construction of functionalized acyclic all‐carbon quaternary stereocenters and 1,3‐nonadjacent stereoelements has been developed via organo/metal dual catalyzed asymmetric allenylic substitution of branched and linear aldehydes, by developing an unknown acyclic secondary‐secondary diamine as the enabling organocatalyst. Although it is believed that secondary‐secondary diamines are difficult to be used as the organocatalysts in organo/metal dual catalysis, this study demonstrates that such diamines can be successfully combined with a metal catalyst in organo/metal dual catalysis. Our study enables the asymmetric construction of two important classes of motifs which were previously difficult to access, axially chiral allene‐containing acyclic all‐carbon quaternary stereocenters and 1,3‐nonadjacent stereoelements bearing allenyl axial chirality and central chirality, in good yields with high enantio‐ and diastereoselectivity. [ABSTRACT FROM AUTHOR]

The palladium‐catalyzed asymmetric carboamination reaction is one of the most significant transformations in organic chemistry. Herein, we report the first palladium‐catalyzed asymmetric alleneamination of β,γ‐unsaturated hydrazones with propargylic acetates. This protocol enables the efficient installation of various multisubstituted allene groups onto dihydropyrazoles in good yields with excellent enantioselectivities. The chiral sulfinamide phosphine ligand Xu‐5 exhibits highly efficient stereoselective control in this protocol. The salient features of this reaction include the readily available starting materials, a broad substrate scope, an easy scale‐up, mild reaction conditions and versatile transformations. [ABSTRACT FROM AUTHOR]

The palladium catalyzed cyclotrimerization of ortho‐silylaryl triflates as aryne precursors is meanwhile an established method to synthesize polycyclic aromatic hydrocarbons (PAHs) with triphenylene cores. During the palladium‐catalyzed reaction of a pyrene with an o‐silylaryl triflate moiety in the K‐region higher homologues with central eight‐ and ten‐membered rings (the pyrenylenes) were found, besides the expected trimer and a protocol was developed to isolate all members of this series. This unprecedented new class of PAHs was fully investigated by all means, including X‐ray diffraction of single‐crystals, UV/Vis and fluorescence spectroscopy and theoretical calculations. Supported by density‐functional theory (DFT) calculations, a mechanism of all higher cyclooligomers is proposed. [ABSTRACT FROM AUTHOR]

"Through space" palladium/hydrogen shift is an efficient strategy to achieve selective functionalization of a specific remote C−H bond. Compared with relatively extensive exploited 1,4‐palladium migration process, the relevant 1,5‐Pd/H shift was far less investigated. We herein report a novel 1,5‐Pd/H shift pattern between a vinyl and an acyl group. Through the pattern, rapid access to 5‐membered‐dihydrobenzofuran and indoline derivatives has been achieved. Further studies have unveiled an unprecedented trifunctionalization (vinylation, alkynylation and amination) of a phenyl ring through 1,5‐palladium migration relayed decarbonylative Catellani type reaction. A series of mechanistic investigations and DFT calculations have provided insights into the reaction pathway. Notably, it was unveiled that the 1,5‐palladium migration in our case prefers a stepwise mechanism involving a PdIV intermediate. [ABSTRACT FROM AUTHOR]

Amide is one of the most widespread functional groups in organic and bioorganic chemistry, and it would be valuable to achieve stereoselective C(sp3)−H functionalization in amide molecules. Palladium(II) catalysis has been prevalently used in the C−H activation chemistry in the past decades, however, due to the weakly‐coordinating feature of simple amides, it is challenging to achieve their direct C(sp3)−H functionalization with enantiocontrol by PdII catalysis. Our group has developed sulfoxide‐2‐hydroxypridine (SOHP) ligands, which exhibited remarkable activity in Pd‐catalyzed C(sp2)−H activation. In this work, we demonstrate that chiral SOHP ligands served as an ideal solution to enantioselective C(sp3)−H activation in simple amides. Herein, we report an efficient asymmetric PdII/SOHP‐catalyzed β‐C(sp3)−H arylation of aliphatic tertiary amides, in which the SOHP ligand plays a key role in the stereoselective C−H deprotonation‐metalation step. [ABSTRACT FROM AUTHOR]

The first hydride‐containing 2‐electron palladium/copper alloys, [PdHCu11{S2P(OiPr)2}6(C≡CPh)4] (PdHCu11) and [PdHCu12{S2P(OiPr)2}5{S2PO(OiPr)} (C≡CPh)4] (PdHCu12), are synthesized from the reaction of [PdH2Cu14{S2P(OiPr)2}6(C≡CPh)6] (PdH2Cu14) with trifluoroacetic acid (TFA). X‐ray diffraction reveals that the PdHCu11 and PdHCu12 kernels consist of a central PdH unit encapsulated within a vertex‐missing Cu11 cuboctahedron and complete Cu12 cuboctahedron, respectively. DFT calculations indicate that both PdHCu11 and PdHCu12 can be considered as axially‐distorted 2‐electron superatoms. PdHCu11 shows excellent HER activity, unprecedented within metal nanoclusters, with an onset potential of −0.05 V (at 10 mA cm−2), a Tafel slope of 40 mV dec−1, and consistent HER activity during 1000 cycles in 0.5 M H2SO4. Our study suggests that the accessible central Pd site is the key to HER activity and may provide guidelines for correlating catalyst structures and HER activity. [ABSTRACT FROM AUTHOR]

Pd‐catalyzed nucleophilic fluorination reactions are important methods for the synthesis of fluoroarenes and fluoroalkenes. However, these reactions can generate a mixture of regioisomeric products that are often difficult to separate. While investigating the Pd‐catalyzed fluorination of cyclic vinyl triflates, we observed that the addition of a substoichiometric quantity of TESCF3 significantly improved the regioselectivity of the reaction. Herein, we report a combined experimental and computational study on the mechanism of this transformation focusing on the role of TESCF3. The poor regioselectivity of the reaction in the absence of additives results from the formation of LPd‐cyclohexyne complexes (L=biaryl monophosphine ligand). When TESCF3 is added to the reaction mixture, the generation of the Pd‐cyclohexyne complexes is diminished by an unexpected pathway involving the dearomatization of the ligand by nucleophilic attack from a trifluoromethyl anion (CF3−). [ABSTRACT FROM AUTHOR]

A rare gyrobifastigium architecture (GB) was constructed by self‐assembly of a tetradentate donor (L) with PdII acceptor in DMSO. The GB was converted to its isomeric tetragonal barrel (MB) upon treatment with water. The hydrophobic cavity of MB has been explored for the encapsulation of zinc‐phthalocyanine (ZnPc), which is an excellent photosensitizer for photodynamic therapy (PDT). However, the poor water‐solubility and aggregation tendency are the main reasons for the suboptimal PDT performance of free ZnPc in the aqueous medium. Effective solubilization of ZnPc in an aqueous medium was achieved by encapsulating it in the cavity of MB. The inclusion complex (ZnPc⊂MB) showed enhanced singlet oxygen generation in water. Higher cellular uptake and anticancer activity of the ZnPc⊂MB compared to free ZnPc on HeLa cells indicate that encapsulation of ZnPc in an aqueous host is a potential strategy for enhancement of its PDT activity in water. [ABSTRACT FROM AUTHOR]

The straightforward access to a new class of aza‐polyaromatics is reported. Starting from readily available fluorinated s‐tetrazine, a cyclization process with azide leads to the formation of an unprecedented tetrazo[1,2‐b]indazole or a bis‐tetrazo[1,2‐b]indazole (cis and trans conformers). Based on the new nitrogen core, further N‐directed palladium‐catalyzed ortho‐C−H bond functionalization allows the introduction of halides or acetates. The physicochemical properties of these compounds were studied by a joint experimental/theoretical approach. The tetrazo[1,2‐b]indazoles display solid‐state π‐stacking, low reduction potential, absorption in the visible range up to the near‐infrared, and intense fluorescence, depending on the molecular structure. [ABSTRACT FROM AUTHOR]

Switching between the formation/dissociation of rotaxanes is important to control the function of various types of rotaxane‐based materials. We have developed a convenient and simple strategy, the so‐called "accelerator addition", to make a static rotaxane dynamic without apparently affecting the chemical structure. As an interlocked molecule that enables tuning of the formation/dissociation speed, a metallorotaxane was quantitatively generated by the complexation of a triptycene‐based dumbbell‐shaped mononuclear complex, [PdL2]2+ (L=2,3‐diaminotriptycene), with 27C9. As a result of the inertness of the Pd2+‐based coordination structure, the metallorotaxane was slowly formed (the static state). This rotaxane formation was accelerated 27 times simply by adding Br− as an accelerator (the dynamic state). A similar drastic acceleration was also demonstrated during the dissociation process when Cs+ was added to the metallorotaxane to form the free axle [PdL2]2+ and the 27C9‐Cs+ complex. [ABSTRACT FROM AUTHOR]

The development of preparative methods for the synthesis of four‐membered carbocycles is gaining increasing importance due to the widespread utility of cyclic compounds in medicinal chemistry. Herein, we report the development of a new methodology for the production of spirocyclic epoxides and aziridines containing a cyclobutane motif. In a two‐step one‐pot process, a bicyclo[1.1.0]butyl sulfoxide is lithiated and added to a ketone, aldehyde or imine, and the resulting intermediate is cross‐coupled with an aryl triflate through C−C σ‐bond alkoxy‐ or aminopalladation with concomitant epoxide or aziridine formation. After careful optimization, a remarkably efficient reaction was conceived that tolerated a broad variety of both aromatic and aliphatic substrates. Lastly, through several high yielding ring‐opening reactions, we demonstrated the excellent applicability of the products as modular building blocks for the introduction of three‐dimensional structures into target molecules. [ABSTRACT FROM AUTHOR]

An efficient double allene protocol for the formation of benzazocines has been developed. The reaction constitutes a highly regioselective palladium‐catalyzed formal [6+2] annulation of allenyl benzoxazinanones with terminal allenes forming the challenging 8‐membered cycles. Decent yields and excellent regioselectivity have been observed under mild conditions with a remarkable Z‐stereoselectivity for the exo‐cyclic C=C bonds. The synthetic potentials of benzazocine products have been demonstrated. [ABSTRACT FROM AUTHOR]

The site‐selective palladium‐catalyzed three‐component coupling of unactivated alkenyl carbonyl compounds, aryl‐ or alkenylboronic acids, and N‐fluorobenzenesulfonimide is described herein. Tuning of the steric environment on the bidentate directing auxiliary enhances regioselectivity and facilitates challenging C(sp3)−F reductive elimination from a PdIV intermediate to afford 1,2‐carbofluorination products in moderate to good yields. [ABSTRACT FROM AUTHOR]

Synergistic catalysis has emerged as one of the most powerful tools for stereodivergent formation of Csp3−Csp3 bonds bearing vicinal stereocenters. Despite the many successes that have been achieved in this field, stereodivergent Csp3−Csp3 coupling reactions involving stabilized nucleophiles remain challenging because of the competing single‐catalysis pathway. Herein, we report a synergistic palladium/phase‐transfer catalyst system that enables diastereodivergent Csp3−Csp3 coupling reactions of 1,3‐dienes with stabilized nucleophile oxindoles. Both the syn and anti coupling products, bearing quaternary and tertiary vicinal stereocenters, could be selectively produced in good yields with high enantio‐ and diastereoselectivities. Non‐covalent activation of the stabilized nucleophile via chiral ion pair in a biphasic system is a crucial success factor in achieving diastereodivergence. [ABSTRACT FROM AUTHOR]

Electronically matched nucleophilic 1,6‐conjugate addition has been well studied and widely applied in synthetic areas. In contrast, nucleophilic 1,5‐conjugate addition represents an electronically forbidden process and is considered unfeasible. Here, we describe modular protocols for 1,5‐conjugate addition reactions via palladium hydride catalysis. Both palladium and synergistic Pd/organocatalyst systems are developed to catalyze 1,5‐conjugate reaction, followed by inter‐ or intramolecular [3+2] cyclization. A migratory 1,5‐addition protocol is established to corroborate the feasibility of this umpolung concept. The 1,5‐addition products are conveniently transformed into a series of privileged enantioenriched motifs, including polysubstituted tetrahydrofuran, dihydrofuran, cyclopropane, cyclobutane, azetidine, oxetane, thietane, spirocycle and bridged rings. Preliminary mechanistic studies corroborate the involvement of palladium hydride catalysis. [ABSTRACT FROM AUTHOR]

The transition‐metal‐catalyzed carbonylation reaction is a useful approach for ketone synthesis. However, it is often problematic to use exogenous carbonyl reagents, such as gaseous carbon monoxide. In this manuscript, we report a novel palladium‐catalyzed coupling reaction of gem‐difluoroalkenes and aryl boronic acids that yields bioactive indane‐type ketones with an all‐carbon α‐quaternary center. Characterization and stoichiometric reactions of the key intermediates RCF2PdII support a water‐induced defluorination and cross‐coupling cascade mechanism. The vinyl difluoromethylene motif serves as an in situ carbonyl precursor which is unprecedented in transition‐metal‐catalyzed coupling reactions. It is expected to raise broad research interest from the perspectives of ketone synthesis, fluoroalkene functionalization, and rational design of new synthetic protocols based on the unique reactivity of difluoroalkyl palladium(II) species. [ABSTRACT FROM AUTHOR]

Chiral perhydroindoles are found in a number of natural products and biologically active compounds. Therefore, the development of new asymmetric methodology for rapid access to this core is of high importance. Herein, we reported a highly regio‐ and diastereo‐selective palladium/PC‐Phos‐catalyzed asymmetric Heck/Tsuji–Trost reactions of readily available amino tethered 1,3‐cyclohexadienes with aryl and alkenyl halides, delivering various functionalized chiral hexahydroindoles in good yields with high enantioselectivity. The application of this reaction to the concise synthesis of (−)‐α‐Lycorane was demonstrated. DFT computation results indicate that the difference in ΔEdis of two migration insertion transition states determines the enantioselectivity of the reaction. [ABSTRACT FROM AUTHOR]

A novel and expedient cascade strategy has been demonstrated for the synthesis of fused benzo‐aza‐oxa‐[5‐6‐5] tetracycles in high yields and diastereoselectivities (up to 20 : 1 dr). The strategy was fulfilled through palladium‐catalyzed oxidative convergent assembly of functionally divergent anilines and 3‐butenoic acid with five chemical bonds constructed. Coupled with control experiments and deuterium labelled studies, DFT calculations were performed for the proposed mechanism. The utility of the illustrated strategy is emphasized by gram‐scale syntheses, late‐stage functionalization, and the transformation to a key core of natural products such as martinellic acid and seneciobipyrrolidine. [ABSTRACT FROM AUTHOR]

Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo‐ and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well‐developed. However, the efficient synthesis of chiral 3‐substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N‐aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5‐tricyclic lactone core structure of Speradine A. [ABSTRACT FROM AUTHOR]

Alkene difunctionalization featuring an intramolecular carbometallation step has been developed into a powerful transformation in organic synthesis. The 5‐exo‐trig carbometallation is in general highly favored over the alternative 6‐endo‐trig cyclization. We report herein a formal 6‐endo‐trig carbofluorination protocol by combining the conventional 5‐exo‐trig carbopalladation with a chemoselective 1,2‐aryl/Pd dyotropic rearrangement. Treatment of 2‐(2‐alkylallyloxy)phenyl boronic acid derivatives in the presence of a catalytic amount of Pd(dba)2, 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine and Selectfluor affords chromanes with concurrent generation of a tertiary alkyl fluoride function. A σ‐alkyl‐PdII species resulting from the 5‐exo‐trig carbopalladation process is isolated and characterized by X‐ray crystallographic analysis. Its oxidation to PdIV complex triggers the chemoselective dyotropic rearrangement leading to the ring expansion product. [ABSTRACT FROM AUTHOR]

An approach allowing remote editing of stacked aromatic assemblies for heteroannular C−H functionalization would represent a transformative chemical toolbox that may make the diversification of complex molecules in a straightforward manner. However, such a C−H activation is usually less kinetically and thermodynamically favorable than homoannular ortho C−H activation and remains a fundamental challenge. Herein we disclose an engineer's approach, using a transient ligand as an interim bridge between two aryl rings (analogues to mountaintops) to anchor the metal center on the remote heteroannular C−H bond. As a proof‐of‐concept, we present the palladium‐catalyzed heteroannular C−H olefination of stacked aromatic assemblies with olefins and allylation with vinyl acetates using L‐tert‐leucine acid as a transient ligand. Mechanistic investigations suggest an unusual olefin coordination‐promoted interannular palladium migration process determinative for reversal of the site‐selectivity. [ABSTRACT FROM AUTHOR]

Enantioselective C−H activation has surfaced as a transformative toolbox for the efficient assembly of chiral molecules. However, despite of major advances in rhodium and palladium catalysis, ruthenium(II)‐catalyzed enantioselective C−H activation has thus far largely proven elusive. In contrast, we herein report on a ruthenium(II)‐catalyzed highly regio‐, diastereo‐ and enantioselective C−H alkylation. The key to success was represented by the identification of novel C2‐symmetric chiral imidazolidine carboxylic acids (CICAs), which are easily accessible in a one‐pot fashion, as highly effective chiral ligands. This ruthenium/CICA system enabled the efficient installation of central and axial chirality, and featured excellent branched to linear ratios with generally >20 : 1 dr and up to 98 : 2 er. Mechanistic studies by experiment and computation were carried out to understand the catalyst mode of action. [ABSTRACT FROM AUTHOR]

The transition‐metal‐catalyzed C−P bond cleavage has emerged as a powerful tool for the formation of both C−C and C−P bond. However, the transition‐metal‐catalyzed stereoselective cleavage of C−P bond is still undeveloped. Herein, we report a palladium‐catalyzed stereoselective cleavage of C−P bond for the construction of P‐stereogenic phosphines and stereogenic axis. This protocol enables the quick synthesis of atropisomers bearing a P‐stereogenic center in high yields, diastereo‐ and enantioselectivities of up to 98 % ee, >25 : 1 dr. The product is able to serve as chiral catalyst in phosphine catalyzed [3+2] cycloaddition of allenoates to imines, showing the great potential of the present methodology. [ABSTRACT FROM AUTHOR]

Controlling regioselectivity in C−H functionalizations is a key challenge in chemical method development. In arenes, functionalizations are most difficult to direct towards the C−H group furthest away from a substituent, in its para position. We herein demonstrate how the para‐C−H arylation of anilines with non‐activated aryl halides, elusive to date, is achieved by a base‐assisted "metalla‐tautomerism" approach. A proton is abstracted from the aniline substrate and replaced by an arylpalladium species, generated from the aryl halide coupling partner. In this step, the palladium is directed away from the N‐ to the tautomeric para‐C−H position by a large phosphine ligand combined with a triphenylmethyl shielding group. The triphenylmethyl group is easily installed and removed, and can be recycled. [ABSTRACT FROM AUTHOR]

N−N Atropisomers are a common motif in natural products and represent a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective synthesis of N−N bisindole atropisomers is unprecedented. Herein, the first enantioselective synthesis of N−N bisindole atropisomers via the palladium‐catalyzed de novo construction of one indole skeleton is presented. A wide variety of N−N axially chiral bisindoles were generated in good yields with excellent enantioselectivities via a cascade condensation/N‐arylation reaction. Structurally diverse indole‐pyrrole, indole‐carbazole, and non‐biaryl‐indole atropisomers possessing a chiral N−N axis were accessed using this protocol. Moreover, investigations using density functional theory (DFT) calculations provided insight into the reaction mechanism and enantiocontrol. [ABSTRACT FROM AUTHOR]