We report a systematic study of the stoichiometric reactions of isolated arylpalladium hydroxo and halide complexes with arylboronic acids and aryltrihydroxyborates to evaluate the relative rates of the two reaction pathways commonly proposed to account for transmetallation in the SuzukiMiyaura reaction. Based on the relative populations of the palladium and organoboron species generated under conditions common for the catalytic process and the observed rate constants for the stoichiometric reactions between the two classes of reaction components, we conclude that the reaction of a palladium hydroxo complex with boronic acid, not the reaction of a palladium halide complex with trihydroxyborate, accounts for transmetallation in catalytic Suzuki-Miyaura reactions conducted with weak base and aqueous solvent mixturesThe Suzuki-Miyaura reaction is one of the most practiced classes of catalytic C-C bond formation. Although this reaction is established to occur by oxidative addition, transmetallation and reductive elimination, the mechanism of the transmetallation step has been widely debated. Two pathways are typically considered for transmetallation: conversion of an organoboron compound by base to form a nucleophilic boronate, followed by attack on a palladium halide complex (Scheme 1, Path A) or conversion of a palladium halide to a nucleophilic palladium hydroxo complex that subsequently reacts with a neutral organoboron compound (Scheme 1, Path B). 1 A number of studies have led to the conclusion that transmetallation occurs between the palladium halide and boronate, but data that indicate transmetallation could occur between the boronic acid and palladium hydroxo species have also been reported. 2,3 Because transmetallation is often proposed to be turnover limiting and to dictate the choice of reaction conditions, a firm understanding of the mechanism of this step is important for the use of this common catalytic process. 4 We report a systematic study involving the reactions of isolated arylpalladium hydroxo complexes and arylpalladium halide complexes containing the same ancillary ligands with arylboronic acids and aryltrihydroxyborates. Equilibrium data for the interconversion of boronic acid and trihydroxyborate, as well as equilibrium constants for the interconversion of palladium hydroxo and halide complexes containing PPh 3 and PCy 3 (Cy=cyclohexyl) as ligands have also been gained. Together, these data provide strong evidence that, in the typical mixtures of water and organic solvent, transmetallation between a palladium center that is ligated by common phosphines, such as PPh 3 or PCy 3 , occurs between the palladium hydroxo complex and a boronic acid, not between the palladium halide complex and a trihydroxyborate, as often proposed.* jhartwig@illinois.edu . Our experimental design to assess the different proposed pathways focused on comparing the relative rates of the different stoichiometric reactions between isolated arylpalladium complexes and arylboron species. We studied the stoichiometr...

The oxidative addition of PhX (X = I, Br, Cl) to the complexes Pd(P t Bu 3 ) 2 (1), Pd(1-AdP t Bu 2 ) 2 (2), Pd(CyP t Bu 2 ) 2 (3), and Pd(PCy 3 ) 2 (4) were studied to determine the effect of steric properties on the coordination number of the species that undergoes oxidative addition and to determine if the type of halide affects the identity of this species. The kinetic data imply that the number of phosphines coordinated to the complex that reacts in the irreversible step of the oxidative addition processes for complexes 1-4 depends on the halide more than the steric properties of the ligands. The rate-limiting step of the oxidative addition of PhI occurred with L 2 Pd (0) 3 . The irreversible step of the oxidative addition of PhCl occurred with a monophosphine species in each case, as signaled by an inverse dependence of the rate constant on the concentration of ligand. The irreversible step of the oxidative addition of PhBr occurred with a bisphosphine species, as signaled by the zeroth-order or small dependence of the rate constant on the concentration of phosphine. Thus, the additions of the less reactive chloroarenes occur through lower-coordinate intermediates than additions of the more reactive haloarenes.

We report here the remarkable properties of PAd3, a crystalline air-stable solid accessible through a scalable SN1 reaction. Spectroscopic data reveal that PAd3, benefiting from the polarizability inherent to large hydrocarbyl groups, exhibits unexpected electron releasing character that exceeds other alkylphosphines and falls within a range dominated by N-heterocyclic carbenes. Dramatic effects in catalysis are also enabled by PAd3 during Suzuki-Miyaura cross-coupling of chloro(hetero)arenes (40 examples) at low Pd loading, including the late-stage functionalization of commercial drugs. Exceptional space-time yields are demonstrated for the syntheses of industrial precursors to valsartan and boscalid from chloroarenes with ∼2 × 10(4) turnovers in 10 min.

The incorporation of polar functional groups into polyolefins can significantly alter the adhesion, barrier and surface properties, dyeability, printability, and compatibility of the resulting "functional polyolefin". Thus, the development of methods for the controlled synthesis of functional polyolefins from industrially relevant monomers holds the potential to expand the range of applications available to this already ubiquitous class of materials. In this Perspective, recent advances in transition-metal-catalyzed functional polyolefin synthesis will be reviewed. A common thread among the innovations discussed here is the perturbation of catalyst function by tailored design of the chelating ancillary ligand, aided in many cases by improved mechanistic understanding. Specific topics discussed here include rare examples of catalyst control over the regio-and stereochemistry of polar monomer insertion by phosphine−sulfonato palladium complexes (Drent-type), rate acceleration of insertion polymerization by binuclear cooperativity using salicylaldiminato nickel complexes (Grubbs-type), and formation of linear copolymers of ethylene and polar vinyl monomers using a cationic palladium catalyst ligated by a bisphosphine monoxide (BPMO) that contrasts the typical polymer microstructures formed by other cationic group 10 catalysts ligated by an α-diimine (Brookhart-type).

The copolymerization of ethylene with polar vinyl monomers, such as vinyl acetate, acrylonitrile, vinyl ethers, and allyl monomers, was accomplished using cationic palladium complexes ligated by a bisphosphine monoxide (BPMO). The copolymers formed by these catalysts have highly linear microstructures and a random distribution of polar functional groups throughout the polymer chain. Our data demonstrate that cationic palladium complexes can exhibit good activity for polymerizations of polar monomers, in contrast to cationic α-diimine palladium complexes (Brookhart-type) that are not applicable to industrially relevant polar monomers beyond acrylates. Additionally, the studies reported here point out that phosphine-sulfonate ligated palladium complexes are no longer the singular family of catalysts that can promote the reaction of ethylene with many polar vinyl monomers to form linear functional polyolefins.

Thioether ancillary ligands have been identified that can greatly accelerate the C-H alkenylation of O-, S-, and N-heteroarenes. Kinetic data suggest thioether-Pd-catalyzed reactions can be as much as 800× faster than classic ligandless systems. Furthermore, mechanistic studies revealed C-H bond cleavage as the turnover-limiting step, and that rate acceleration upon thioether coordination is correlated to a change from a neutral to a cationic pathway for this key step. The formation of a cationic, low-coordinate catalytic intermediate in these reactions may also account for unusual catalyst-controlled site selectivity wherein C-H alkenylation of five-atom heteroarenes can occur under electronic control with thioether ligands even when this necessarily involves reaction at a more hindered C-H bond. The thioether effect also enables short reaction times under mild conditions for many O-, S-, and N-heteroarenes (55 examples), including examples of late-stage drug derivatization.

Oxidative C–H/C–H coupling is a promising synthetic route for the streamlined construction of conjugated organic materials for optoelectronic applications. Broader adoption of these methods is nevertheless hindered by the need for catalysts that excel in forging core semiconductor motifs, such as ubiquitous oligothiophenes, with high efficiency in the absence of metal reagents. We report a (thioether)­Pd-catalyzed oxidative coupling method for the rapid assembly of both privileged oligothiophenes and challenging hindered cases, even at low catalyst loading under Ag- and Cu-free conditions. A combined experimental and computational mechanistic study was undertaken to understand how a simple thioether ligand, MeS­(CH2)3SO3Na, leads to such potent reactivity toward electron-rich substrates. The consensus from these data is that a concerted, base-assisted C–H cleavage transition state is operative, but thioether coordination to Pd is associated with decreased synchronicity (bond formation exceeding bond breaking) versus the “standard” concerted metalation–deprotonation (CMD) model that was formalized by Fagnou in direct arylation reactions. Enhanced positive charge buildup on the substrate results from this perturbation, which rationalizes experimental trends strongly favoring π-basic sites. The term electrophilic CMD (eCMD) is introduced to distinguish this mechanism from the standard model, even though both mechanisms locate in a broad concerted continuum. More O’Ferrall–Jencks analysis further suggests eCMD should be a general mechanism manifested by many metal complexes. A preliminary classification of complexes into those favoring eCMD or standard CMD is proposed, which should be informative for studies toward tunable catalyst-controlled reactivity.

We report the isolation and reactivity of a series of “ligandless,” anionic arylpalladium complexes of the general structure [Pd(Ar)Br2]22- by the reaction of (tBu3P)Pd(Ar)(Br) and bromide. These anionic complexes insert olefins at room temperature, and these fast insertions indicate that the anionic complexes are kinetically competent as intermediates in Heck-Mizoroki reactions conducted under “ligandless” conditions (lacking added dative ligand). Kinetic studies showed that the anionic complexes insert olefins much faster than the corresponding neutral, P(t-Bu)3-ligated complexes. Addition of halide to the reaction of the neutral complex (tBu3P)Pd(Ar)(Br) and styrene led to a significant rate acceleration, suggesting that the anionic complex forms rapidly and reversibly in situ from the neutral species prior to migratory insertion. These data, along with studies on the regioselectivity for reaction of aryl halides with butyl vinyl ether in the presence of the different starting catalysts, are consistent with the intermediacy of the same anionic, arylpalladium intermediates in Heck reactions catalyzed by palladium complexes containing bulky trialkylphosphine ligands as in reactions conducted under ligandless conditions.