Interrogating Explicit Solvent Effects on the Mechanism and Site-Selectivity of Aryl Halide Oxidative Addition to L2Pd(0).

We report a study of solvent effects on the rate, selectivity, and mechanism of (hetero)aryl (pseudo)halide oxidative addition to Pd(PCy3)2 as an exemplar of L2Pd(0) species. First, 2-chloro-3-aminopyridine is observed to undergo faster oxidative addition in toluene compared to more polar solvents, which is not consistent with the trend we observe with many other 2-halopyridines. We attribute this to solvent basicity hydrogen-bonding (pKHB) between solvent and substrate. Greater hydrogen-bond donation from the substrate leads to a more electron-rich aromatic system, and therefore slower oxidative addition. We demonstrate how this affects rate and site-selectivity for hydrogen-bond donating substrates. Second, electron-deficient multihalogenated pyridines exhibit improved site-selectivity in polar solvents, which we attribute to different C-X sites undergoing oxidative addition by two different mechanisms. The C-X site that favours the more polar nucleophilic displacement transition state is preferred over the site that favours a less-polar 3-centered transition state. Finally, (hetero)aryl triflates consistently undergo faster oxidative addition in more polar solvents, which we attribute to highly polar nucleophilic displacement transition states. This leads to improved site-selectivity for C-OTf oxidative addition, even in the presence of highly reactive 2-pyridylhalides.

Metal Activation Produces Different Reaction Environments for Intermediates during Oxidative Addition.

Commercial zinc metal powder requires activation for consistent and reliable use as a reductant in the formation of organozinc reagents from organohalides, and for the avoidance of supplier and batch-to-batch variability. However, the impact of activation methods on the reaction environments of subsequent intermediates has been unknown. Herein, a fluorescence lifetime imaging microscopy (FLIM) method is developed to bridge this knowledge gap, by imaging and examining reaction intermediates on zinc metal that has been activated by pretreatment through different common methods (i. e., by chemical activation with TMSCl, dibromoethane, or HCl; or by mechanical activation). The group of chemical activating agents, previously thought to act similarly by removing oxide layers, are here shown to produce markedly different reaction environments experienced by subsequent oxidative-addition intermediates from organohalides - data uniquely available through FLIM's ability to detect small quantities of intermediates in situ coupled with its microenvironmental sensitivity. These different microenvironments potentially give rise to different rates of formation, subsequent solubilization, and reactivity, despite the shared "[RZnX]" molecular structure of these intermediates. This information revises models for methods development for oxidative addition to currently sluggish metals beyond zinc by establishing diverse outcomes for pretreatment activation methods that were previously considered similar.

Quantitative Reactivity Models for Oxidative Addition to L2Pd(0): Additional Substrate Classes, Solvents, and Mechanistic Insights.

Quantitative molecular structure-reactivity models are useful for generating predictions to guide synthesis design, and in formulating and testing mechanistic hypotheses. We report an expanded multivariate linear regression (MLR) model for the rate of (hetero)aryl (pseudo)halide oxidative addition to L2Pd(0), here exemplified by Pd(PCy3)2. This builds on a prior model from our group, with additional substrate classes (aryl chlorides and iodides) and reaction solvents (THF, toluene, THF/DMF mixture). Overall solvent effects across the entire substrate set are minimal under these conditions, enabling a unified MLR model without introduction of new molecular descriptors beyond the original five. Examining the mechanistic origin of the two molecular electrostatic potential (ESP) descriptors led to generation of a simpler, four descriptor model that is suitable for aryl halides, but not for 2-halopyridines. Using this model we identified a mechanistic outlier, 2-pyridyl triflate, which undergoes a nucleophilic displacement oxidative addition that does not involve the adjacent nitrogen atom. Finally, we discuss the relationship between C-X bond strength and oxidative addition rates, and compare the intrinsic bond strength index (IBSI) to bond dissociation enthalpy (BDE) as a bond strength descriptor.

Sequential H/D Exchanges Resulting from Rollover-Cyclometallation during Photoirradiation of Rhodium(III) Complex in Methanol-d4.

We present the photoreaction of newly prepared bis(6,6'-dimethyl-2,2'-bipyridine)(oxalato)rhodium(III) ([Rh(N^N)2(ox)]+) in CD3OD. Photoirradiation of this complex causes the dissociation of ox, followed by the formation of the unprecedented Rh(III) complex with Rh-H and Rh-C s bonds, [Rh(N^N)(C^N)(H)(CD3OD)]+ (C^N = [6,6'-dimethyl-2,2'-bipyridine]-3-yl-κC3,κN1'). This hydride formation and cyclometallation spontaneously proceed owing to the conflict between the steric hindrance arising from the methyl groups of N^N and the driving force for the structural change due to [Rh(N^N)2]+ formation. Although [Rh(N^N)(C^N)(H)(CD3OD)]+ is initially converted to [Rh(N^N)2]+ by photoirradiation, it is immediately regenerated by the rollover cyclometallation of the [Rh(N^N)2]+ complex. [Rh(N^N)(C^N)(H)(CD3OD)]+ undergoes H/D exchange for the H atoms in the Rh-H bond and at the 3, 3'-positions of the N^N ligand during the photoirradiation. DFT calculations predict with reasonable certainty the spontaneous structural change of [Rh(N^N)2]+ to [Rh(N^N)(C^N)(H)(CD3OD)]+ and the subsequent photodriven Rh-C bond rupture leading to the formation of [Rh(N^N)2]+ accompanied by H/D exchange reactions.

A Deeper Insight into the Supramolecular Activation of Oxidative Addition Reactions Involving Pincer-Rhodium(I) Complexes.

The factors governing the acceleration of the oxidative addition of methyl iodide to pincer rhodium(I)-complexes induced by coronene have been computationally explored in detail using quantum chemical methods. Both the parent reaction and the coronene-mediated process proceed via a stepwise SN2-type mechanism. It is found that the acceleration of the process derives from the formation of an initial supramolecular complex, mainly stabilized by electrostatic and π-π interactions, which significantly increases the electron richness of the complex. The impact of this effect on the reaction barrier has been quantitatively analyzed by applying the activation strain model in combination with the energy decomposition analysis method. In addition, the influence of other polycyclic aromatic hydrocarbons on the oxidative reaction has been also considered.

Polar X-H Bond (X=O, S, N) Activation at a Cage Silanide.

Low-valent silicon compounds such as neutral silylenes display versatile reactivity for the activation of small molecules. In contrast, their anionic congeners silanides ([R3 Si- ]) have primarily been investigated for their nucleophilic reactivity. Here we show that incorporating a silanide center in a bicyclic cage structure allows for formal oxidative addition of polar element-hydrogen bonds (RX-H, R=aromatic residue, X=O, S, NH). The resulting hydrosilicates were isolated and characterized structurally and spectroscopically. Density Functional Theory (DFT) calculations and experimental observations support an ionic mechanism for RX-H bond activation. Finally, the reactivity of the RS-H bond adduct was further investigated, revealing that it behaves as a Lewis pair upon facile heterolytic cleavage of the Si-S bond.

Rapid aminations of functionalized aryl fluorosulfates in water.

Aryl fluorosulfates of varying complexities have been used in amination reactions in water using a new Pd oxidative addition complex (OAC-1) developed specifically to match the needs of the fine chemicals industry, not only in terms of functional group tolerance, but also reflecting time considerations associated with these important C-N couplings. Also especially noteworthy is that they replace both PFAS-related triflates and nonaflates, which are today out of favor due to recent government regulations. The new complex based on the BippyPhos ligand is used at low loadings and under aqueous micellar conditions. Moreover, it is easily prepared and stable to long term storage. DFT calculations on the OAC precatalyst compare well with the X-ray structure of the crystals with π-complexation to the aromatic system of the ligand and also confirm the NMR data showing a mixture of conformers in solution that differ from the X-ray structure in rotation of the phenyl and t-butyl ligand substituents. An extensive variety of coupling partners, including pharmaceutically relevant APIs, readily participate under mild and environmentally responsible reaction conditions.

Oxidative Addition of E-H (E=C, N) Bonds to Transient Uranium(II) Centers.

Two-electron oxidative addition is one of the most important elementary reactions for d-block transition metals but it is uncommon for f-block elements. Here, we report the first examples of intermolecular oxidative addition of E-H (E=C, N) bonds to uranium(II) centers. The transient U(II) species was formed in-situ by reducing a heterometallic cluster featuring U(IV)-Pd(0) bonds with potassium-graphite (KC8). Oxidative addition of C-H or N-H bonds to the U(II) centers was observed when this transient U(II) species was treated with benzene, carbazole or 1-adamantylamine, respectively. The U(II) centers could also react with tetracene, biphenylene or N2O, leading to the formation of arene reduced U(IV) products and uranyl(VI) species via two- or four-electron processes. This study demonstrates that the intermolecular two-electron oxidative addition reactions are viable for actinide elements.

Oxidative Addition and ß-Hydride Elimination by a Macrocyclic Dinickel Complex: Observing Bimetallic Elementary Reactions.

The dinickel(I) complex Ni2 (tBu PONNOPONNO), featuring a planar macrocyclic diphosphoranide ligand tBu PONNOPONNO, offers a unique architectural platform for observing bimetallic elementary reactions. Oxidative addition reactions of alkyl halides produce dinickel(II) complexes of the type Ni2 (µ-R)(µ-X)(tBu PONNOPONNO). However, when R=Et ß-hydride elimination is observed to form a dinickel monohydride, with the rate dependent on the nature of X. DFT studies suggest a new mechanism for bimetallic ß-hydride elimination, where the rate dependence arises from the steric pressure imposed by the X group on the opposing trans face of the dinickel macrocycle. This work enhances understanding of bimetallic elementary reactions, particularly ß-hydride elimination, which have not been well-explored for dinuclear systems.

Palladium(0)-Catalyzed Anti-Selective Addition-Cyclizations of Alkynyl Electrophiles.

Palladium(0)/monophosphine complexes catalyze anti-selective alkylative, arylative, and alkynylative cyclizations of alkynyl electrophiles with organometallic reagents. The remarkable anti-selectivity results from novel oxidative addition, that is, the nucleophilic attack of electron-rich palladium(0) on the electrophile across the alkyne followed by transmetalation and reductive elimination ("anti-Wacker"-type cyclization). With regard to 5-alkynals, triphenylphosphine (PPh3 )-ligated palladium(0) catalyzes the cyclization of terminal alkynes and conjugated alkenyl- or alkynyl-substituted ones to afford 2-cyclohexen-1-ol and 2-alkylidene-cyclopentanol derivatives, respectively. For 6-alkyl- or 6-aryl-5-alkynals, the cyclization does not proceed with the palladium/PPh3 catalyst; however, it does proceed with palladium/tricyclohexylphosphine (PCy3 ), to yield the former products predominantly. Remarkably, the latter catalyst completely switches the regioselectivity in the cyclization of the conjugated diyne-aldehydes. Notably, palladium/PPh3 -catalyzed cyclizations also proceed with other organometallics or even without them.

Three Oxidative Addition Routes of Alkali Metal Aluminyls to Dihydridoaluminates and Reactivity with CO2.

Three distinct routes are reported to the soluble, dihydridoaluminate compounds, AM[Al(NONDipp )(H)2 ] (AM=Li, Na, K, Rb, Cs; [NONDipp ]2- =[O(SiMe2 NDipp)2 ]2- ; Dipp=2,6-iPr2 C6 H3 ) starting from the alkali metal aluminyls, AM[Al(NONDipp )]. Direct H2 hydrogenation of the heavier analogues (AM=Rb, Cs) produced the first examples of structurally characterized rubidium and caesium dihydridoaluminates, although harsh conditions were required for complete conversion. Using 1,4-cyclohexadiene (1,4-CHD) as an alternative hydrogen source in transfer hydrogenation reactions provided a lower energy pathway to the full series of products for AM=Li-Cs. A further moderation in conditions was noted for the thermal decomposition of the (silyl)(hydrido)aluminates, AM[Al(NONDipp )(H)(SiH2 Ph)]. Probing the reaction of Cs[Al(NONDipp )] with 1,4-CHD provided access to a novel inverse sandwich complex, [{Cs(Et2 O)}2 {Al(NONDipp )(H)}2 (C6 H6 )], containing the 1,4-dialuminated [C6 H6 ]2- dianion and representing the first time that an intermediate in the commonly utilized oxidation process of 1,4-CHD to benzene has been trapped. The synthetic utility of the newly installed Al-H bonds has been demonstrated by their ability to reduce CO2 under mild conditions to form the bis-formate AM[Al(NONDipp )(O2 CH)2 ] compounds, which exhibit a diverse series of eyecatching bimetallacyclic structures.

Base-Triggered Oxidative Addition to Gold.

The coordination of secondary phosphine oxides (SPO) was shown to efficiently promote the activation of C(sp2 )-I bonds by gold, as long as a base is added (NEt3 , K2 CO3 ). These transformations stand as a new type of chelation-assisted oxidative addition to gold. The role of the base and the influence of the electronic properties of the P-ligand were analyzed computationally. Accordingly, the oxidative addition was found to be dominated by Au→(Ar-I) backdonation. In this case, gold behaves similarly to palladium, suggesting that the inverse electron flow reported previously (with prevailing (Ar-I)→Au donation, resulting in faster reactions of electron-enriched substrates) is a specific feature of electron-deficient cationic gold(I) complexes. The reaction gives straightforward access to (P=O,C)-cyclometallated Au(III) complexes. The possibility to chemically derivatize the SPO moiety at Au(III) was substantiated by protonation and silylation reactions.

The Role of Inverted Ligand Field in the Electronic Structure and Reactivity of Octahedral Formal Platinum (IV) Complexes.

Platinum complexes are ubiquitous in chemistry and largely used as catalysts or as precursors in drug chemistry, thus a deep knowledge of their electronic properties may help in planning new synthetic strategies or exploring new potential applications. Herein, the electronic structure of many octahedral platinum complexes is drastically revised especially when they feature electronegative elements such as halogens and chalcogens. The investigation revealed that in most cases the five d platinum orbitals are invariably full, thus the empty antibonding orbitals, usually localized on the metal, are mainly centered on the ligands, suggesting a questionable assignment of formal oxidation state IV. The analysis supports the occurrence of the inverted ligand field theory in all cases with the only exceptions of the Pt-F and Pt-O bonding. The trends for the molecular complexes are mirrored also by the density of states plots of extended structures featuring octahedral platinum moieties in association with chalcogens atoms. Finally, the oxidative addition of a Se-Cl linkage to a square platinum complex to achieve an octahedral moiety has been revised in the framework of the inverted ligand field.

Bromobenzene Transforms Lanthanoid Pseudo-Grignard Chemistry.

Divalent lanthanoid pseudo-Grignard reagents PhLnBr (Ln=Sm, Eu and Yb) can be easily prepared by the oxidative addition of bromobenzene (PhBr) to lanthanoid metals in tetrahydrofuran (THF). PhLnBr reacts with bulky N,N'-bis(2,6-di-isopropylphenyl)formamidine (DippFormH) to generate LnII complexes, namely [Ln(DippForm)Br(thf)3 ]2 ⋅6thf (1; Sm, 2; Eu), and [Yb(DippForm)Br(thf)2 ]2 ⋅2thf (3; Yb). Samarium and europium (in 1 and 2) are seven coordinate, whereas ytterbium (in 3) is six coordinate, and all are bromine-bridged dimers. When PhLnBr reacts with 3,5-diphenylpyrazole (Ph2 pzH), both divalent (5; [Eu(Ph2 pz)2 (thf)4 ]) and trivalent (4 a; [Sm(Ph2 pz)3 (thf)3 ]⋅3thf, 4 b; [Sm(Ph2 pz)3 (dme)2 ]⋅dme) complexes are obtained. In the monomeric compounds 4(a,b), samarium is nine coordinate but europium is eight coordinate in 5. The use of PhLnBr in this work transforms the outcomes from earlier reactions of PhLnI.

Spectral Physics of Stable Cu(III) Produced by Oxidative Addition of an Alkyl Halide.

In this paper, we theoretically investigated spectral physics on Cu(III) complexes formed by the oxidative addition of α-haloacetonitrile to ionic and neutral Cu(I) complexes, stimulated by recent experimental reports. Firstly, the electronic structures of reactants of α-haloacetonitrile and neutral Cu(I) and two kinds of products of Cu(III) complexes are visualized with the density of state (DOS) and orbital energy levels of HOMO and LUMO. The visually manifested static and dynamic polarizability as well as the first hyperpolarizability are employed to reveal the vibrational modes of the normal and resonance Raman spectra of two Cu(III) complexes. The nuclear magnetic resonance (NMR) spectra are not only used to identify the reactants and products but also to distinguish between two Cu(III) complexes. The charge difference density (CDD) reveals intramolecular charge transfer in electronic transitions in optical absorption spectra. The CDDs in fluorescence visually reveal electron-hole recombination. Our results promote a deeper understanding of the physical mechanism of stable Cu(III) produced by the oxidative addition of an alkyl halide.

The Reactions of Alkenes with Phenyl-N-triflylimino-λ3-iodane: Solvent and Oxidant Impact.

The reactions of alkenes with phenyl-N-triflylimino-λ3-iodane PhI=NTf (1) have been studied in different conditions. In methylene chloride, in the presence of N-halosuccinimides, the products of mono and bis-triflamidation were obtained. In MeCN, the product of bromotriflamidation (with NBS) with solvent interception or of bis-triflamidation (with NIS) is formed. The reaction with trans-stilbene in acetonitrile with NBS gave rise to cyclization to 2-methyl-4,5-diphenyl-1-triflyl-4,5-dihydro-1H-imidazole. In contrast, with NIS as an oxidant, both in CH2Cl2 and MeCN, the major product was 2,3-diphenyl-1-triflylaziridine formed in good yield. With NBS, aziridine is also formed but as a minor product, the major one being a mixture of diastereomers of the product of bromotriflamidation. The reaction of compound 1 with vinylcyclohexane in methylene chloride affords the mixtures of regioisomers of the products of halotriflamidation, whereas in acetonitrile, the products of solvent interception and cyclization to the imidazoline are formed. A mechanism explaining the formation of all isolated products is proposed.

Four-Electron Oxidative Addition of an N=N Double Bond at a Chromium Metallocyclopropene.

This report describes the synthesis of a pseudo-tetrahedral chromium alkyne complex supported by a bidentate phosphinimide ligand and its reactivity with an azobenzene derivative. Characterization of the former by structural and computational methods reveals an unprecedented extent of alkyne activation by a formal chromium(II) center, suggesting that this complex is best described as a chromium(IV)-metallocyclopropene. Exposure of this compound to 4,4'-difluoroazobenzene results in the formation of a chromium(VI) diimido complex, which constitutes a rare 4-electron oxidative addition of an N=N double bond. The isolation of a chromium(IV)-hydrazido intermediate enabled mechanistic investigations of this challenging bond cleavage process. This work substantiates the notion that terminal phosphinimide ligands can engender first-row transition metal ions with exceptional reactivity.

A Hemilabile NHC-Gold Complex and its Application to the Redox Neutral 1,2-Oxyarylation of Feedstock Alkenes.

We describe a AuI complex of a hemi-labile (C^N) N-heterocyclic carbene ligand that is able to mediate oxidative addition of aryl iodides. Detailed computational and experimental investigations have been undertaken to verify and rationalize the oxidative addition process. Application of this initiation mode has resulted in the first examples of "exogenous oxidant-free" AuI /AuIII catalyzed 1,2-oxyarylations of ethylene and propylene. These demanding yet powerful processes establish these commodity chemicals as nucleophilic-electrophilic building blocks in catalytic reaction design.

Trimethylsilyl Chloride Aids in Solubilization of Oxidative Addition Intermediates from Zinc Metal.

Trimethylsilyl chloride (TMSCl) is commonly used to "activate" metal(0) powders toward oxidative addition of organohalides, but knowledge of its mechanism remains limited by the inability to characterize chemical intermediates under reaction conditions. Here, fluorescence lifetime imaging microscopy (FLIM) overcomes these prior limitations and shows that TMSCl aids in solubilization of the organozinc intermediate from zinc(0) metal after oxidative addition, a previously unknown mechanistic role. This mechanistic role is in contrast to previously known roles for TMSCl before the oxidative addition step. To achieve this understanding, FLIM, a tool traditionally used in biology, is developed to characterize intermediates during a chemical reaction-thus revealing mechanistic steps that are unobservable without fluorescence lifetime data. These findings impact organometallic reagent synthesis and catalysis by providing a previously uncharacterized mechanistic role for a widely used activating agent, an understanding of which is suitable for revising activation models and for developing strategies to activate currently unreactive metals.

Reversible Dihydrogen Activation and Catalytic H/D Exchange with Group 10 Heterometallic Complexes.

Reaction of a hexagonal planar palladium complex featuring a [PdMg3 H3 ] core with H2 is reversible and leads to the formation of a new [PdMg2 H4 ] tetrahydride species alongside an equivalent of a magnesium hydride co-product [MgH]. While the reversibility of this process prevented isolation of [PdMg2 H4 ], analogous [PtMg2 H4 ] and [PtZn2 H4 ] complexes could be isolated and characterised through independent syntheses. Computational analysis (DFT, AIM, NCIPlot) of the bonding in a series of heterometallic tetrahydride compounds (Ni-Pt; Mg and Zn) suggests that these complexes are best described as square planar with marginal metal-metal interactions; the strength of which increases slightly as group 10 is descended and increases from Mg to Zn. DFT calculations support a mechanism for H2 activation involving a ligand-assisted oxidative addition to Pd. These findings were exploited to develop a catalytic protocol for H/D exchange into magnesium hydride and zinc hydride bonds.