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This report describes a combined experimental and computational investigation of the mechanism of C(sp(3))-N bond-forming reductive elimination from sulfonamide-ligated Pd(IV) complexes. After an initial experimental assessment of reactivity, we used ZStruct, a computational combinatorial reaction finding method, to analyze a large number of multistep mechanisms for this process. This study reveals two facile isomerization pathways connecting the experimentally observed Pd(IV) isomers, along with two competing SN2 pathways for C(sp(3))-N coupling. One of these pathways involves an unanticipated oxygen-nitrogen exchange of the sulfonamide ligand prior to an inner-sphere SN2-type reductive elimination. The calculated ΔG(⧧) values for isomerization and reductive elimination with a series of sulfonamide derivatives are in good agreement with experimental data. Furthermore, the simulations predict relative reaction rates with different sulfonamides, which is successful only after considering competition between the proposed operating mechanisms. Overall, this work shows that the combination of experimental studies and new computational tools can provide fundamental mechanistic insights into complex organometallic reaction pathways.

Optimized conditions are elaborated in detail for the title process and NMe4F is found to be generally more cost-effective than CsF.

A Pd-catalyzed asymmetric alkene 1,2-dioxygenation reaction is described. The diastereoselectivity of the reaction is controlled by tethering a chiral oxime ether directing group to the alkene substrate. The best selectivities are obtained with 8-substituted menthone-derived oxime ether auxiliaries.

This paper describes a photoredox palladium/iridium-catalyzed C–H arylation with diaryliodonium reagents. Details of the reaction optimization, substrate scope, and mechanism are presented along with a comparison to a related method in which aryldiazonium salts are used in place of diaryliodonium reagents. The unprecedentedly mild reaction conditions (25 ºC in methanol), the requirement for light and a photocatalyst, the inhibitory effect of radical scavengers, and the observed chemoselectivity trends are all consistent with a radical-thermal reaction with diaryliodonium reagents that is believed to proceed via an ‘ionic’ 2e− pathway and requires a much higher reaction temperature (100 ºC).

Trifluoromethyl-substituted arenes and heteroarenes are widely prevalent in pharmaceuticals and agrochemicals. As a result, the development of practical methods for the formation of aryl–CF3 bonds has become an active field of research. Over the past five years, transition-metal-catalyzed cross-coupling between aryl–X (X = halide, organometallic, or H) and various ‘CF3’ reagents has emerged as a particularly attractive approach to generating aryl–CF3 bonds. Despite many recent advances in this area, current methods generally suffer from limitations such as poor generality, harsh reaction conditions, the requirement for stoichiometric quantities of metals, and/or the use of costly CF3 sources. This Account describes our recent efforts to address some of these challenges by: (1) developing aryltrifluoromethylation reactions involving high oxidation state Pd intermediates, (2) exploiting AgCF3 for C–H trifluoromethylation, and (3) achieving Cu-catalyzed trifluoromethylation with photogenerated CF3 •. 1 Introduction 2 Part 1. Aryltrifluoromethylation via High-Valent Palladium 3 Part 2. Aryltrifluoromethylation Using AgCF3 4 Part 3. Cu-Catalyzed Aryltrifluoromethylation with CF3• 5 Outlook

The palladium-catalyzed C-H fluorination of 8-methylquinoline derivatives with nucleophilic fluoride is reported. This transformation involves the use of AgF as the fluoride source in combination with a hypervalent iodine oxidant. Both the scope and mechanism of the reaction are discussed.

This report describes the synthesis of Rh(III) complexes containing a pyridinium-substituted bipyridine ligand. The catalytic activity of these complexes in H/D exchange reactions between arenes and acetic acid-d4 has been evaluated.

This communication describes the development of a mild method for the cross-coupling of arylboronic acids with CF(3)I via the merger of photoredox and Cu catalysis. This method has been applied to the trifluoromethylation of electronically diverse aromatic and heteroaromatic substrates and tolerates many common functional groups.

This report describes a comparison of the reactivity of a series of diimine PtII complexes as catalysts for H/D exchange between benzene and RCO2D. Substitution at the 2- and 6-positions of the N-aryl group and especially incorporation of halogens at these sites lead to significant increases in catalyst reactivity. Interestingly, marked differences in the structure activity relationship were observed in this catalytic study compared to previously reported stoichiometric investigations of C–H activation at PtII diimine complexes.

This paper describes the synthesis of a series of PdIV complexes containing modular monoanionic tridentate facially coordinated NNN and NNC donor ligands. In all cases, these complexes are stable to reductive elimination for a minimum of several days in solution at room temperature. With appropriately designed tridentate ligands, the PdIV adducts participate in both ligand substitution and C–H activation reactions. Overall, this work shows that unsymmetrical fac-L2X type ligands can serve as versatile and tunable scaffolds for modulating the reactivity of octahedral PdIV complexes.

This communication demonstrates the homogeneous hydrogenation of CO(2) to CH(3)OH via cascade catalysis. Three different homogeneous catalysts, (PMe(3))(4)Ru(Cl)(OAc), Sc(OTf)(3), and (PNN)Ru(CO)(H), operate in sequence to promote this transformation.

This paper describes density functional theory (DFT) calculations of the mechanism of carbon-acetate bond-forming reductive elimination from Pd centers. This C–O coupling reaction has been studied ...

This communication describes the first observation and study of C-H activation at a Pd(IV) center. This transformation was achieved by designing model complexes in which the rate of reductive elimination is slowed relative to that of the desired C-H activation process. Remarkably, the C-H activation reaction can proceed under mild conditions and with complementary site selectivity to analogous transformations at Pd(II). These results provide a platform for incorporating this new reaction as a step in catalytic processes.

The silver-mediated C-H trifluoromethylation of aromatic substrates using TMSCF(3) is described. The development, optimization, and scope of these transformations are reported. AgCF(3) intermediates are proposed.

Tuning the aryl substituents of N,N′-diaryl-2,3-dimethyl-1,4-diaza-1,3-butadiene (DAB) ligands promotes the challenging C–C bond-forming reductive elimination from PtIV diimine complexes [(DAB)Pt(CH3)3(solvent)]+ (2) under mild conditions. Experimental results and density functional calculations indicate that 2,6-aryl substitution promotes reductive elimination by facilitating dissociation of the coordinating solvent by close to 10 kcal mol–1, but too much steric bulk inhibits the formation of 2 in the one-electron outersphere oxidation of (DAB)Pt(CH3)2 (1).

This article describes the rational design of first generation systems for oxidatively induced Aryl-CF(3) bond-forming reductive elimination from Pd(II). Treatment of (dtbpy)Pd(II)(Aryl)(CF(3)) (dtbpy = di-tert-butylbipyridine) with NFTPT (N-fluoro-1,3,5-trimethylpyridinium triflate) afforded the isolable Pd(IV) intermediate (dtbpy)Pd(IV)(Aryl)(CF(3))(F)(OTf). Thermolysis of this complex at 80 °C resulted in Aryl-CF(3) bond-formation. Detailed experimental and computational mechanistic studies have been conducted to gain insights into the key reductive elimination step. Reductive elimination from this Pd(IV) species proceeds via pre-equilibrium dissociation of TfO(-) followed by Aryl-CF(3) coupling. DFT calculations reveal that the transition state for Aryl-CF(3) bond formation involves the CF(3) acting as an electrophile with the Aryl ligand serving as a nucleophilic coupling partner. These mechanistic considerations along with DFT calculations have facilitated the design of a second generation system utilizing the tmeda (N,N,N',N'-tetramethylethylenediamine) ligand in place of dtbpy. The tmeda complexes undergo oxidative trifluoromethylation at room temperature.

This paper describes the 1,1-arylacetoxylation of diverse α-olefins using organostannanes and hypervalent iodine oxidants. The reaction provides a convergent approach for generating a C-C and a C-O bond as well as a new stereocenter in a single catalytic transformation.

This letter describes a new method for the highly site- and chemoselective Pd-catalyzed direct arylation of naphthalene. Tuning the structure of the diimine-ligated Pd catalyst results in formation of the α-arylated product in high yield and >50:1 selectivity. This is, to our knowledge, the first systematic evaluation of catalyst control in the C−H arylation of an unactivated aromatic substrate. Preliminary studies implicate an unusual mechanism involving sequential naphthalene π-coordination/metalation at PdIV.

The palladium-catalyzed direct arylation of 2,5-substituted pyrrole derivatives with diaryliodonium salts to generate tri-, tetra-, and penta-substituted pyrrole products is described. The scope and limitations of these transformations are also reported.

The disproportionation of 2 equiv of (L)2Pd(CH3)(X) to form 1 equiv of (L)2Pd(CH3)2 and 1 equiv of (L)2Pd(X)2 could serve as a key step in the catalytic oxidative oligomerization of methane. The thermodynamics associated with this transformation have been evaluated as a function of the supporting ligands L and X using DFT calculations. With these calculations as a guide, we demonstrate the first experimental example of disproportionation of a PdII monomethyl complex to generate a PdII dimethyl species using (tBu-bpy)Pd(CH3)(CH2COCH3) (tBu-bpy = 4,4′-di-tert-butyl-2,2′-bipyridine) as the starting material.

This article describes the synthesis, characterization, and reactivity of palladium(II) fluoride complexes containing sp(2) and sp(3) nitrogen-containing supporting ligands. Both cis and trans complexes of general structure (N)(N')Pd(II)(R)(F) (R = Ar or CH(3)) as well as cis-(N)(2)Pd(II)(F)(2) are reported. Crystallographic characterization of these molecules has allowed structural comparisons to related phosphine-ligated species. Furthermore, these studies have revealed that nitrogen-donor ligands support some of the longest and the shortest Pd-F bonds reported to date. The thermal decomposition of (N)(N')Pd(II)(R)(F) has also been examined, and no products of C-F bond-forming reductive elimination were obtained in any case.

O-Acetyl oximes serve as effective directing groups for Pd-catalyzed sp(2) and sp(3) C-H functionalization reactions. The C-H functionalization products can be subsequently transformed into ortho- or beta-functionalized ketones, alcohols, amines, and heterocycles.

This paper describes an efficient synthesis of the cationic platinum complex [(N-CH3-bpym)PtCl2]+ (N-CH3-bpym = N-methylbipyrimidinium) and evaluation of its catalytic activity in H/D exchange reactions of CH4 (with D2SO4) and benzene (with CF3CO2D). With both substrates [(N-CH3-bpym)PtCl2]+ shows C−H activation reactivity comparable to that of its neutral analogue (bpym)PtCl2 (bpym = bipyrimidine). The origin of this similar reactivity is proposed to be the in situ formation of the same active catalyst in both cases.

This paper describes a protocol for the direct comparison of diverse Pt catalysts in the H/D exchange between C6H6 and TFA-d1, CD3CO2D, and TFE-d3 using turnover number (TON) as a standard metric. An initial survey of Pt complexes, including commercial Pt salts (PtCl2, K2PtCl4) and Pt chloride complexes containing bidentate and tridentate nitrogen donor ligands, has been conducted. These studies have established that the addition of AgOAc (in TFA-d1) or AgBF4 (in CD3CO2D and TFE-d3) displaces the Cl ligands on the Pt precatalyst, which leads to dramatically increased turnover numbers. In general, PtCl2 and K2PtCl4 provided the fewest turnovers, and species containing bidentate ligands afforded higher turnover numbers than those with tridentate ligands. A diimine Pt complex was found to be a top performing catalyst for H/D exchange with all deuterium sources examined. Interestingly, the relative reactivity of many of the catalysts varied dramatically upon changing the deuterium source, highlighting the nee...

This paper describes the oxidation of PtII(phpy)2 (phpy = 2-phenylpyridine) with two different electrophilic chlorinating reagents—PhICl2 and N-chlorosuccinimide (NCS). PtII(phpy)2 reacts with PhICl2 to provide the PtIV complex PtIVCl2(phpy)2 as a mixture of symmetrical and unsymmetrical isomers. In contrast, the reaction of PtII(phpy)2 with NCS affords a mixture of the PtIII dimer [(phpy)2(Cl)PtIII]2 and PtIVCl2(phpy)2, whose ratio varies as a function of reaction time, concentration, and the presence/absence of ambient light. The implications of these results for the mechanisms of the two reactions are discussed in detail.

Palladium(II) complexes containing bidentate cyclometalated C∼N chelating ligands are shown to react with PhINTs at room temperature to insert “NTs” into the Pd−C bond. This “NTs” insertion reaction has been applied to palladacyclic complexes of azobenzene, benzo[h]quinoline, and 8-ethylquinoline. The newly aminated organic ligands can be liberated from the metal center by protonolysis with trifluoroacetic acid or HCl.

A copper-mediated radiofluorination of aryl- and vinylboronic acids with K(18)F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [(18)F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors.

The integration of renewable energy sources into the electric grid requires low-cost energy storage systems that mediate the variable and intermittent flux of energy associated with most renewables. Nonaqueous redox-flow batteries have emerged as a promising technology for grid-scale energy storage applications. Because the cost of the system scales with mass, the electroactive materials must have a low equivalent weight (ideally 150 g/(mol·e(-)) or less), and must function with low molecular weight supporting electrolytes such as LiBF4. However, soluble anolyte materials that undergo reversible redox processes in the presence of Li-ion supports are rare. We report the evolutionary design of a series of pyridine-based anolyte materials that exhibit up to two reversible redox couples at low potentials in the presence of Li-ion supporting electrolytes. A combination of cyclic voltammetry of anolyte candidates and independent synthesis of their corresponding charged-states was performed to rapidly screen for the most promising candidates. Results of this workflow provided evidence for possible decomposition pathways of first-generation materials and guided synthetic modifications to improve the stability of anolyte materials under the targeted conditions. This iterative process led to the identification of a promising anolyte material, N-methyl 4-acetylpyridinium tetrafluoroborate. This compound is soluble in nonaqueous solvents, is prepared in a single synthetic step, has a low equivalent weight of 111 g/(mol·e(-)), and undergoes two reversible 1e(-) reductions in the presence of LiBF4 to form reduced products that are stable over days in solution.

SNAr fluorination of chloro- and nitro arenes is accomplished using acyl azolium fluorides, generated from acyl fluorides and an N-heterocyclic carbene.

This communication describes the synthesis and reactivity of Ni(IV)(aryl)(CF3)2 complexes supported by trispyrazolylborate and 4,4'-di-tert-butylbipyridine ligands. We demonstrate that isolable Ni(IV) complexes can be accessed under mild conditions via the oxidation of Ni(II) precursors with S-(trifluoromethyl)dibenzothiophenium triflate as well as with diaryliodonium and aryl diazonium reagents. The Ni(IV) intermediates undergo high yielding aryl-CF3 bond-forming reductive elimination. These studies support the potential viability of Ni(IV) intermediates in nickel-catalyzed coupling reactions involving diaryliodonium and aryldiazonium electrophiles.

The direct functionalization of carbon–hydrogen (C–H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C–H bond activation, catalytic processes that utilize a PdII/PdIV redox cycle are increasingly common. The C–H activation step in most of these catalytic cycles is thought to occur at a PdII centre. However, a number of recent reports have suggested the feasibility of C–H cleavage occurring at PdIV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at PdII. This mini review highlights proposed examples of C–H activation at PdIV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed.

Palladium-catalyzed ligand directed C–H activation/halogenation reactions have been extensively explored. Both the nature of the directing group and the substitution pattern on the arene ring of the substrate lead to different reactivity profiles, and often different and complementary products, in the presence and absence of the catalyst.

This paper describes the palladium-catalyzed oxidative functionalization of arene and alkane C–H bonds using the polymer-immobilized iodine(III) oxidant poly-4-(diacetoxyiodo)styrene (PS–I(OAc)2) and its derivatives. These transformations have been applied to a wide range of organic substrates, and typically proceed with excellent levels of regio- and chemoselectivity as well as with high functional group tolerance. In addition, the polymer-immobilized iodine(I) byproducts of these reactions are readily recovered (by precipitation with methanol), reoxidized (with inexpensive peracetic acid), and reused in multiple catalytic transformations without significant loss of reactivity. Variation of the substituents at the iodine(III) center allows the installation of diverse functionalities, including carbon–oxygen, carbon–chlorine, and carbon–carbon bonds.

[reaction: see text] This paper describes the application of peroxide-based oxidants in the Pd(OAc)(2)-catalyzed acetoxylation and etherification of arene and alkane C-H bonds. Oxone in acetic acid and/or methanol proved particularly effective, and these transformations were applied to a wide variety of substrates.

The synthesis of (CN)PtII(acac) complexes (CN = benzo[h]quinoline, 8-methylquinoline) and their oxidation with PhI(OAc)2 are reported as a model system for palladium-catalyzed C−H bond functionalization. Dimeric PtIII−PtIII complexes containing a bridging acetate ligand are obtained in HOAc, and monomeric PtIV complexes incorporating alkoxide and acetate ligands are obtained in MeOH, EtOH, and iPrOH. The implications of these results for the mechanism of analogous Pd-catalyzed reactions is discussed.

This communication describes the activation of CO2 at the Ru pincer complex (PNN)Ru(H)(CO) (PNN = 6-(di-tert-butylphosphinomethylene)-2-(N,N-diethylaminomethyl)-1,6-dihydropyridine). The reaction proceeds to completion within minutes at room temperature to form a C–C bond between the pincer ligand and the electrophilic carbon atom of CO2. The characterization of both the kinetic and thermodynamic products of CO2 activation and the reversibility of this C–C bond formation are discussed.

This Communication describes the hydrogenation of carbon dioxide to methanol via tandem catalysis with dimethylamine and a homogeneous ruthenium complex. Unlike previous examples with homogeneous catalysts, this CO2-to-CH3OH process proceeds under basic reaction conditions. The dimethylamine is proposed to play a dual role in this system. It reacts directly with CO2 to produce dimethylammonium dimethylcarbamate, and it also intercepts the intermediate formic acid to generate dimethylformamide. With the appropriate selection of catalyst and reaction conditions, >95% conversion of CO2 was achieved to form a mixture of CH3OH and dimethylformamide.

The last 2–3 years have seen numerous relationships develop between organometallic chemists, fluorine chemists and PET Centers around the world. These collaborations have led to the development of many new strategies for the late-stage introduction of fluorine-18 into complex bioactive molecules. In this perspective we highlight recent developments and key milestones since 2011.

This paper describes the fluorination of nitrogen heterocycles using anhydrous NBu4F. Quinoline derivatives as well as a number of 3- and 5-substituted pyridines undergo high-yielding fluorination at room temperature using this reagent. These results with anhydrous NBu4F compare favorably to traditional halex fluorinations using alkali metal fluorides, which generally require temperatures of ≥100 °C.

The last 2–3 years have seen numerous relationships develop between organometallic chemists, fluorine chemists and PET Centers around the world. These collaborations have led to the development of many new strategies for the late-stage introduction of fluorine-18 into complex bioactive molecules. In this perspective we highlight recent developments and key milestones since 2011.

The preparation of diaryl and alkyl aryl sulfides via acid-mediated coupling of thiols and thioethers with diaryliodonium salts is reported. The scope, limitations, and mechanism of the transformation are discussed.

This article describes the high-yielding and selective oxidatively induced formation of ethane from mono-methyl palladium complexes. Mechanistic details of this reaction have been explored via both experiment and computation. On the basis of these studies, a mechanism involving methyl group transmetalation between Pd(II) and Pd(IV) interediates is proposed.

Copper plays a dual role: to coordinate both the aryl and fluoride ligands and to serve as an oxidant generating the reactive Cu(III) key intermediate.

The first example of a Pt-catalyzed direct C—H arylation of simple arenes (I), (IV), and (VI) with diaryliodonium salts (II) is described.

This communication describes the design of a model system that allows direct investigation of competing sp(3)-C-N and sp(3)-C-F bond-forming reductive elimination from a Pd(IV) fluoro sulfonamide complex. The reductive elimination selectivity varies dramatically as a function of reaction additives. A mechanism is proposed that provides a rationale for these effects.

Pd-catalyzed oxidative acetoxylation of benzenes is studied using hypervalent iodine acetates.

Unsymmetrical diaryliodonium tetrafluoroborates having an aryl and a mesityl substituent react with KF in the presence of Cu(II)-catalysts to give preferentially the corresponding aryl fluorides and only minor amounts of mesityl fluoride.