Mechanistic studies on direct arylation of pyridine N-oxide: evidence for cooperative catalysis between two distinct palladium centers

Direct arylations of pyridine N-oxide (PyO), a convenient method to prepare 2-arylpyridines, catalyzed by Pd(OAc)(2) and PtBu(3) have been proposed to occur by the generation of a PtBu(3)-ligated arylpalladium acetate complex, (PtBu(3))Pd(Ar)(OAc) (1), and the reaction of this complex with PyO. We provide strong evidence that 1 does not react directly with PyO. Instead, our data imply that the cyclometalated complex [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2), which is generated from the decomposition of 1, reacts with PyO and serves as a catalyst for the reaction of PyO with 1. The reaction of PyO with 1 occurs with an induction period, and the reaction of 1 with excess PyO in the presence of [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) is zeroth-order in 1. Moreover, the rates of reactions of PyO with bromobenzene catalyzed by [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) and [Pd(PtBu(3))(2)] depend on the concentration of [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) but not on the concentration of [Pd(PtBu(3))(2)]. Finally, the reaction of 1 with a model heteroarylpalladium complex containing a cyclometalated phosphine, [(PEt(3))Pd(2-benzothienyl)(tBu(2)PCMe(2)CH(2))], rapidly formed the arylated heterocycle. Together, these data imply that the rate-determining C-H bond cleavage occurs between PyO and the cyclometalated [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) rather than between PyO and 1. In this case, the resulting heteroarylpalladium complex transfers the heteroaryl group to 1, and C-C bond-formation occurs from (PtBu(3))Pd(Ar)(2-pyridyl oxide). This mechanism proposed for the direct arylation of PyO constitutes an example of C-H bond functionalization in which C-H activation occurs at one metal center and the activated moiety undergoes functionalization after transfer to a second metal center.     

Synthesis, structure, theoretical studies, and Ligand exchange reactions of monomeric, T-shaped arylpalladium(II) halide complexes with an additional, weak agostic interaction

A series of monomeric arylpalladium(II) complexes LPd(Ph)X (L = 1-AdPtBu2, PtBu3, or Ph5FcPtBu2 (Q-phos); X = Br, I, OTf) containing a single phosphine ligand have been prepared. Oxidative addition of aryl bromide or aryl iodide to bis-ligated palladium(0) complexes of bulky, trialkylphosphines or to Pd(dba)2 (dba = dibenzylidene acetone) in the presence of 1 equiv of phosphine produced the corresponding arylpalladium(II) complexes in good yields. In contrast, oxidative addition of phenyl chloride to the bis-ligated palladium(0) complexes did not produce arylpalladium(II) complexes. The oxidative addition of phenyl triflate to PdL2 (L = 1-AdPtBu2, PtBu3, or Q-phos) also did not form arylpalladium(II) complexes. The reaction of silver triflate with (1-AdPtBu2)Pd(Ph)Br furnished the corresponding arylpalladium(II) triflate in good yield. The oxidative addition of phenyl bromide and iodide to Pd(Q-phos)2 was faster than oxidative addition to Pd(1-AdPtBu2)2 or Pd(PtBu3)2. Several of the arylpalladium complexes were characterized by X-ray diffraction. All of the arylpalladium(II) complexes are T-shaped monomers. The phenyl ligand, which has the largest trans influence, is located trans to the open coordination site. The complexes appear to be stabilized by a weak agostic interaction of the metal with a ligand C-H bond positioned at the fourth-coordination site of the palladium center. The strength of the Pd.H bond, as assessed by tools of density functional theory, depended upon the donating properties of the ancillary ligands on palladium.     

Synthesis,characterization, and reactivity of monomeric,arylpalladium halide complexes with a hindered phosphine as the only dative ligand

We report the isolation and structural characterization of several monomeric arylpalladium(II) halide complexes containing tri-tert-butyl phosphine, 1-adamantyl-di-tert-butylphosphine, or 2-adamantyl-di-tert-butylphosphine. X-ray diffraction, IR spectroscopy, and theoretical studies indicated that the complexes may be stabilized by agostic interactions. For example, the distance from the closest hydrogen atom to the palladium metal center in the X-ray structure of the 1-adamantyl-phenylpalladium bromide complex 1 was 2.26(3) A. The calculated Pd-H distance of 2.28 A and harmonic vibrational frequencies were in agreement with the measured distance, but Wiberg bond indices indicated only weak M-H-C interactions. Addition of 2-adamantyl-di-tert-butyl phosphine to 1 led to ligand exchange and formation of 2-adamantyl-di-tert-butyl phosphine complex 2. Addition of P(t-Bu)(3) generated free aryl bromide and Pd[P(t-Bu)(3)](2). Reactivity of complex 1 with nucleophiles provided evidence of the intermediacy of these complexes in palladium-catalyzed cross-coupling reactions. Complex 1 reacted with amine and base to form the corresponding arylamine, with tert-butoxide to form the corresponding ether, with boronic acid and fluoride to form the corresponding biaryl, and with styrene to form stilbene. This complex also catalyzed the reaction of bromobenzene with diphenylamine in the presence of base to produce 94% of the amination product in 45 min at room temperature. This rate is comparable to the reaction rate of in situ generated catalysts.     

Mechanistic analysis of iridium(III) catalyzed direct C-H arylations: a DFT study

In a recent experimental work the Ir complex [Ir(cod)(py)(PCy(3))](PF(6)) (that is, Crabtree's catalyst) has been shown to catalyze the C-H arylation of electron-rich heteroarenes with iodoarenes using Ag(2)CO(3) as base. For this process, an electrophilic metalation mechanism, (S(E)Ar) has been proposed as operative mechanism rather than the concerted metalation-deprotonation (CMD) mechanism, widely implicated in Pd-catalyzed arylation reactions. Herein we have investigated the C-H activation step for several (hetero)arenes catalyzed by a Ir(III) catalyst and compared the data obtained with the results for the Pd(II)-catalyzed C-H bond activation. The calculations demonstrate that, similar to Pd(II)-catalyzed reactions, the Ir(III)-catalyzed direct C-H arylation occurs through the CMD pathway which accounts for the experimentally observed regioselectivity. The transition states for Ir(III)-catalyzed direct C-H arylation feature stronger metal-C((arene)) interactions than those for Pd(II)-catalyzed C-H arylation. The calculations also demonstrate that ligands with low trans effect may decrease the activation barrier of the C-H bond cleavage.     

Highly efficient carbazolyl-derived phosphine ligands: application to sterically hindered biaryl couplings

A new family of phosphine ligands bearing a bulky carbazolyl scaffold is described. With the combination of ligand 2a and Pd(OAc)(2), difficult tri-ortho-substituted biaryl couplings are accomplished smoothly. In particular, the catalyst loading as low as 0.02 mol% of Pd for non-activated 2,6-disubstituted aryl chloride coupling can be achieved.     

Evidence for in situ catalyst modification during the Pd-catalyzed conversion of aryl triflates to aryl fluorides

A mechanistic investigation of the Pd-catalyzed conversion of aryl triflates to fluorides is presented. Studies reveal that C-F reductive elimination from a LPd(II)(aryl)F complex (L = t-BuBrettPhos or RockPhos) does not occur when the aryl group is electron rich. Evidence is presented that a modified phosphine, generated in situ, serves as the actual supporting ligand during catalysis with such substrates. A preliminary study of the reactivity of a LPd(II)(aryl)F complex based on this modified ligand is reported.     

Pd(OAc)2-catalyzed oxidative coupling reaction of benzenes with olefins in the presence of molybdovanadophosphoric acid under atmospheric dioxygen and air

The direct oxidative coupling reaction of benzenes with alkenes bearing an electron-withdrawing group was successfully achieved by the use of Pd(OAc)(2)/molybdovanadophosphoric acid (HPMoV) as the key catalyst under O(2) or air atmosphere. Thus, the reaction of benzene with ethyl acrylate under air (1 atm) assisted by Pd(OAc)(2)/HPMoV afforded ethyl cinnamate as a major product in satisfactory yield (74%). This catalytic system could be extended to the coupling reactions between various substituted benzenes and alkenes through the direct aromatic C-H bond activation. In the reaction of benzene with ethyl acrylate under O(2) (1 atm), the best turn-over number (TON) of Pd(OAc)(2) reached was 121. This reaction provides a green route to cinnamate derivatives, which are important precursors of a variety of pharmaceuticals.     

Key mechanistic features of enantioselective C-H bond activation reactions catalyzed by [(chiral mono-N-protected amino acid)-Pd(II)] complexes

Monoprotected chiral amino acids have recently been established as a class of ligand scaffolds for effecting Pd-catalyzed enantioselective C-H bond activation reactions. However, to elucidate the mechanistic details and controlling factors of these reactions, more comprehensive studies are needed. In this work we report computational investigations into the key mechanistic features of enantioselective C-H bond activation reactions catalyzed by a [chiral (mono-N-protected amino acid)-Pd(II)] complex. Structural analysis points to a C-H insertion intermediate in which the nitrogen atom of the ligand is bound as a neutral σ-donor. The formation of this C-H insertion intermediate could, in principle, proceed via a "direct C-H cleavage" or via "initial N-H bond cleavage followed by C-H cleavage". The computational studies presented herein show that the pathway initiated by N-H bond cleavage is more kinetically favorable. It is shown that the first step of the reaction is the N-H bond cleavage by the coordinated acetate group (OAc). In the next stage, the weakly coordinated OAc(-) (the second acetate group) activates the ortho-C-H bond of the substrate and transfers the H-atom from the C-atom to the bound N-atom of the ligand. As a result, a new Pd-C bond is formed and the carbamate is converted from X-type to L-type ligand. The absolute configuration of the products that are predicted on the basis of the calculated energies of the transition states matches the experimental data. The calculated enantioselectivity is also comparable with the experimental result. On the basis of these data, the origin of the enantioselectivity can be largely attributed to steric repulsions in the transition states.     

Pd/PR3-catalyzed cross-coupling of aromatic carboxylic acids with electron-deficient polyfluoroarenes via combination of decarboxylation with sp2 C-H cleavage

By using Pd(TFA)(2)/PCy(3) as a catalyst, a broad range of aromatic carboxylic acids, including heteroaromatic carboxylic acids, efficiently underwent decarboxylative coupling with an array of polyfluoroarenes in the presence of stoichiometric amount of silver salts to generate biaryls. Silver salts were adjusted to the reactivity of aromatic carboxylic acids to efficiently suppress the protodecarboxylation and therefore improve decarboxylative cross-couplings. It was established that the palladium complex containing the PCy(3) ligand was capable of catalyzing the decarboxylation of electron-rich aromatic carboxylic acids, and silver salts promoted the decarboxylation of both electron-rich and -deficient ones. To explain the two different decarboxylation processes, two possible reaction pathways are proposed, which were further supported by the facts that the stoichiometric arylpalladium complex can directly arylate pentafluorobenzene in the presence of PCy(3) and the arylpalladium complex can catalyze the decarboxylative coupling of 2,4-dimethoxybenzoic acid with pentafluorobenzene. The kinetic isotope effect of 4.0 clearly showed that the C-H bond cleavage of polyfluoroarenes is involved in the rate-determining step.     

Bis-N-heterocyclic carbene palladium(IV) tetrachloride complexes: synthesis, reactivity, and mechanisms of direct chlorinations and oxidations of organic substrates

This Article describes the preparation and isolation of novel octahedral CH(2)-bridged bis-(N-heterocyclic carbene)palladium(IV) tetrachlorides of the general formula LPd(IV)Cl(4) [L = (NHC)CH(2)(NHC)] from LPd(II)Cl(2) and Cl(2). In intermolecular, nonchelation-controlled transformations LPd(IV)Cl(4) reacted with alkenes and alkynes to 1,2-dichlorination adducts. Aromatic, benzylic, and aliphatic C-H bonds were converted into C-Cl bonds. Detailed mechanistic investigations in the dichlorinations of alkenes were conducted on the 18VE Pd(IV) complex. Positive solvent effects as well as kinetic measurements probing the impact of cyclohexene and chloride concentrations on the rate of alkene chlorination support a Pd(IV)-Cl ionization in the first step. Product stereochemistry and product distributions from various alkenes also support Cl(+)-transfer from the pentacoordinated Pd(IV)-intermediate LPd(IV)Cl(3)(+) to olefins. 1-Hexene/3-hexene competition experiments rule out both the formation of π-complexes along the reaction coordinate as well as in situ generated Cl(2) from a reductive elimination process. Instead, a ligand-mediated direct Cl(+)-transfer from LPd(IV)Cl(3)(+) to the π-system is likely to occur. Similarly, C-H bond chlorinations proceed via an electrophilic process with in situ formed LPd(IV)Cl(3)(+). The presence of a large excess of added Cl(-) slows cyclohexene chlorination while the presence of stoichiometric amounts of chloride accelerates both Pd(IV)-Cl ionization and Cl(+)-transfer from LPd(IV)Cl(3)(+). (1)H NMR titrations, T1 relaxation time measurements, binding isotherms, and Job plot analysis point to the formation of a trifurcated Cl(-)···H-C bond in the NHC-ligand periphery as a supramolecular cause for the accelerated chemical events involving the metal center.     

Theoretical analysis of the mechanism of palladium(II) acetate-catalyzed oxidative Heck coupling of electron-deficient arenes with alkenes: effects of the pyridine-type ancillary ligand and origins of the meta-regioselectivity

A systematic theoretical study is carried out on the mechanism for Pd(II)-catalyzed oxidative cross-coupling between electron-deficient arenes and alkenes. Two types of reaction pathways involving either a sequence of initial arene C-H activation followed by alkene activation, or the reverse sequence of initial alkene C-H activation followed by arene activation are evaluated. Several types of C-H activation mechanisms are discussed including oxidative addition, σ-bond metathesis, concerted metalation/deprotonation, and Heck-type alkene insertion. It is proposed that the most favored reaction pathway should involve an initial concerted metalation/deprotonation step for arene C-H activation by (L)Pd(OAc)(2) (L denotes pyridine type ancillary ligand) to generate a (L)(HOAc)Pd(II)-aryl intermediate, followed by substitution of the ancillary pyridine ligand by alkene substrate and direct insertion of alkene double bond into Pd(II)-aryl bond. The rate- and regio-determining step of the catalytic cycle is concerted metalation/deprotonation of arene C-H bond featuring a six-membered ring transition state. Other mechanism alternatives possess much higher activation barriers, and thus are kinetically less competitive. Possible competing homocoupling pathways have also been shown to be kinetically unfavorable. On the basis of the proposed reaction pathway, the regioselectivity predicted for a number of monosubstituted benzenes is in excellent agreement with experimental observations, thus, lending further support for our proposed mechanism. Additionally, the origins of the regioselectivity of C-H bond activation is elucidated to be caused by a major steric repulsion effect of the ancillary pyridine type ligand with ligands on palladium center and a minor electronic effect of the preinstalled substituent on the benzene ring on the cleaving C-H bond. This would finally lead to the formation of a mixture of meta and para C-H activation products with meta products dominating while no ortho products were detected. Finally, the multiple roles of the ancillary pyridine type ligand have been discussed. These insights are valuable for our understanding and further development of more efficient and selective transition metal-catalyzed oxidative C-H/C-H coupling reactions.     

Autocatalysis for C-H bond activation by ruthenium(II) complexes in catalytic arylation of functional arenes

Kinetic data for the C-H bond activation of 2-phenylpyridine by Ru(II)(carboxylate)(2)(p-cymene) I (acetate) and I' (pivalate) are available for the first time. They reveal an irreversible autocatalytic process catalyzed by the coproduct HOAc or HOPiv (acetonitrile, 27 °C). The overall reaction is indeed accelerated by the carboxylic acid coproduct and water. It is retarded by a base, in agreement with an autocatalytic process induced by HOAc or HOPiv that favors the dissociation of one carboxylate ligand from I and I' and consequently the ensuing complexation of 2-phenylpyridine (2-PhPy). The C-H bond activation initially delivers Ru(O(2)CR)(o-C(6)H(4)-Py)(p-cymene) A or A', containing one carboxylate ligand (OAc or OPiv, respectively). The overall reaction is accelerated by added acetates. Consequently, C-H bond activation (faster for acetate I than for pivalate I') proceeds via an intermolecular deprotonation of the C-H bond of the ligated 2-PhPy by the acetate or pivalate anion released from I or I', respectively. The 18e complexes A and A' easily dissociate, by displacement of the carboxylate by the solvent (also favored by the carboxylic acid), to give the same cationic complex B(+) {[Ru(o-C(6)H(4)-Py)(p-cymene)(MeCN)](+)}. Complex B(+) is reactive toward oxidative addition of phenyl iodide, leading to the diphenylated 2-pyridylbenzene.     

Trans influence on the rate of reductive elimination. Reductive elimination of amines from isomeric arylpalladium amides with unsymmetrical coordination spheres

To determine the trans effect on the rates of reductive eliminations from arylpalladium(II) amido complexes, the reactions of arylpalladium amido complexes bearing symmetrical and unsymmetrical DPPF (DPPF = bis(diphenylphosphino)ferrocene) derivatives were studied. THF solutions of LPd(Ar)(NMeAr') (L = DPPF, DPPF-OMe, DPPF-CF3, DPPF-OMe,Ph, DPPF-Ph,CF3, and DPPF-OMe,CF3; Ar = C6H4-4-CF3; Ar' = C6H4-4-CH3, Ph, and C6H4-4-OMe) underwent C-N bond forming reductive elimination at -15 C to form the corresponding N-methyldiarylamine in high yield. Complexes ligated by symmetrical DPPF derivatives with electron-withdrawing substituents on the DPPF aryl groups underwent reductive elimination faster than complexes ligated by symmetrical DPPF derivatives with electron-donating substituents on the ligand aryl groups. Studies of arylpalladium amido complexes containing unsymmetrical DPPF ligands revealed several trends. First, the complex with the weaker donor trans to nitrogen and the stronger donor trans to the palladium-bound aryl group underwent reductive elimination faster than the regioisomeric complex with the stronger donor trans to nitrogen and the weaker donor trans to the palladium-bound aryl group. Second, the effect of varying the substituents on the phosphorus donor trans to the nitrogen was larger than the effect of varying the substituents on the phosphorus donor trans to the palladium-bound aryl group. Third, the difference in rate between the isomeric arylpalladium amido complexes was similar in magnitude to the differences in rates resulting from conventional variation of substituents on the symmetric phosphine ligands. This result suggests that the geometry of the complex is equal in importance to the donating ability of the dative ligands. The ratio of the differences in rates of reaction of the isomeric complexes was similar to the relative populations of the two geometric isomers. This result and consideration of transition state geometries suggest that the reaction rates are controlled more by substituent effects on ground state stability than on transition state energies. In addition, variation of the aryl group at the amido nitrogen showed systematically that complexes with more electron-donating groups at nitrogen undergo faster reductive elimination than those with less electron-donating groups at nitrogen.     

Pd(OAc)(2)-catalyzed oxidative C-H/C-H cross-coupling of electron-deficient polyfluoroarenes with simple arenes

Pd(OAc)(2)-catalyzed intermolecular C-H/C-H cross-coupling reactions between electron-deficient polyfluoroarenes and simple arenes for the synthesis of fluorinated biaryls have been developed. Deuterium-labeling experiments suggested that C-H bond cleavage of the simple arenes rather than the polyfluoroarenes is involved in the rate-limiting step.     

Enynylation of 2-iodo-4-(phenylchalcogenyl)-1-butenes via intramolecular chelation: approach to the synthesis of conjugated dienynes or trienynes

[reaction: see text] 2-Iodo-4-(phenylchalcogenyl)-1-butenes 3 and 4, which are derived from methylenecyclopropanes 1, can be enynylated with alkynes catalyzed by Pd(OAc)(2) to give conjugated dienynes 5 and 6 in the absence of any phosphine ligand and copper salt, and trienyne 9a can be obtained by oxidation of compound 5a. A plausible reaction mechanism has been proposed.     

Mechanistic Study of Palladium-Catalyzed Oxidative C-H/C-H Coupling of Polyfluoroarenes with Simple Arenes

Pd-catalyzed oxidative C-H/C-H coupling reaction is an emerging type of C-H acti-vation reaction, which attracts great interests because both reaction partners do not re-quire pre-functionalization. In the present study, we employed DFT methods to investigatethe mechanism of Pd(OAc)₂-catalyzed oxidative C-H/C-H coupling of pentafluoroben-zene with benzene. Four possible pathways were examined in the C-H activation part: path A benzene-pentafluorobenzene mechanism (C-H activation of benzene occurs before the C-H activation of pentafluorobenzene), path B pentafluorobenzene-benzene mechanism (C-H activation of benzene occurs after the C-H activation of pentafluorobenzene), path C benzene-pentafluorophenylsilver mechanism (C-H activation of benzene and subsequenttransmetalation with pentafluorophenyl silver complex), path D pentafluorophenylsilver-benzene mechanism (transmetalation with pentafluorophenyl silver complex and subsequent C-H activation of benzene). Based on the calculations, the sequences of two C-H activation steps are found to be different in the oxidative couplings of same substrates (i.e. pentaflu-orobenzene and benzene) in different catalytic systems, where the additive Ag salts played a determinant role. In the absence of Ag salts, the energetically favored pathway is path B (i.e. the C-H activation of pentafluorobenzene takes place before the C-H cleavage of benzene). In contrast, with the aid of Ag salts, the coordination of pentafluorophenylsilver to Pd center could occur easily with a subsequent C-H activation of benzene in the second step, and the second step significantly raises the whole reaction barrier. Alternatively, in thepresence of Ag salts, the kinetically preferred mechanism is path C (i.e. the C-H activation of benzene takes place in the first step followed by transmetalation with pentafluorophenyl-silver complex), which is similar to path A. The calculations are consistent with the H/D exchange experiment and kinetic isotope effects. Thus the present study not only offers a deeper understanding of oxidative C-H/C-H coupling reaction, but also provides helpful insights to further development of more efficient and selective oxidative C-H/C-H coupling reactions.     

Drastic effect of bidentate phosphine ligands on Pd-catalyzed hydroarylation of ethyl propiolate: a simple route to arylbutadienes

Palladium complexes with bidentate phosphine ligands, Pd(dppe)(OAc)(2) and Pd(dppm)(OAc)(2), were found to be effective catalysts for reactions of simple arenes with ethyl propiolate, affording arylbutadiene derivatives selectively.     

Mechanism of the mild functionalization of arenes by diboron reagents catalyzed by iridium complexes. Intermediacy and chemistry of bipyridine-ligated iridium trisboryl complexes

This paper describes mechanistic studies on the functionalization of arenes with the diboron reagent B(2)pin(2) (bis-pinacolato diborane(4)) catalyzed by the combination of 4,4'-di-tert-butylbipyridine (dtbpy) and olefin-ligated iridium halide or olefin-ligated iridium alkoxide complexes. This work identifies the catalyst resting state as [Ir(dtbpy)(COE)(Bpin)(3)] (COE = cyclooctene, Bpin = 4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl). [Ir(dtbpy)(COE)(Bpin)(3)] was prepared by independent synthesis in high yield from [Ir(COD)(OMe)](2), dtbpy, COE, and HBpin. This complex is formed in low yield from [Ir(COD)(OMe)](2), dtbpy, COE, and B(2)pin(2). Kinetic studies show that this complex reacts with arenes after reversible dissociation of COE. An alternative mechanism in which the arene reacts with the Ir(I) complex [Ir(dtbpy)Bpin] after dissociation of COE and reductive elimination of B(2)pin(2) does not occur to a measurable extent. The reaction of [Ir(dtbpy)(COE)(Bpin)(3)] with arenes and the catalytic reaction of B(2)pin(2) with arenes catalyzed by [Ir(COD)(OMe)](2) and dtbpy occur faster with electron-poor arenes than with electron-rich arenes. However, both the stoichiometric and catalytic reactions also occur faster with the electron-rich heteroarenes thiophene and furan than with arenes, perhaps because eta(2)-heteroarene complexes are more stable than the eta(2)-arene complexes and the eta(2)-heteroarene or arene complexes are intermediates that precede oxidative addition. Kinetic studies on the catalytic reaction show that [Ir(dtbpy)(COE)(Bpin)(3)] enters the catalytic cycle by dissociation of COE, and a comparison of the kinetic isotope effects of the catalytic and stoichiometric reactions shows that the reactive intermediate [Ir(dtbpy)(Bpin)(3)] cleaves the arene C-H bond. The barriers for ligand exchange and C-H activation allow an experimental assessment of several conclusions drawn from computational work. Most generally, our results corroborate the conclusion that C-H bond cleavage is turnover-limiting, but the experimental barrier for this bond cleavage is much lower than the calculated barrier.     

Unexpected hydrodeiodo Sonogashira-Heck-Casser coupling reaction of 2,2'-diiodobiphenyls with acetylenes

2,2'-Diiodobiphenyl-4,4'-dicarboxylic acid dimethyl ester (3) undergoes either a ring-closure reaction with phenylacetylene to give 4 or hydrodeiodo phenylethynylation to give 5 under the catalytic conditions of Pd(OAc)(2)/CuI/phosphine in amines. In these reactions, the amine and the phosphine ligands play important roles in controlling the reactivity. Among the ligands we used, tris(o-tolyl)phosphine is the best ligand for hydrodeiodo phenylethynylation, while the bidentate phosphine ligand retards both of the reactions. On the basis of our results, we propose that 5 is formed through a fast hydrodeiodination, followed by a Sonogashira phenylethynylation. The results of the deuterium labeling experiments show that proton exchange between the acetylenic proton and the alkyl protons of amine occurs effectively under the reaction conditions. In addition, the hydrogen that replaces the iodide in the hydrodeiodination process arises mainly from the acetylenic proton.     

Reevaluation of the mechanism of the amination of aryl halides catalyzed by BINAP-ligated palladium complexes

Two previous mechanistic studies of the amination of aryl halides catalyzed by palladium complexes of 1,1'-binaphthalene-2,2'-diylbis(diphenylphosphine) (BINAP) are reexamined by the authors of both studies. This current work includes a detailed study of the identity of the BINAP-ligated palladium complexes present in reactions of amines with aryl halides and rate measurements of these catalytic reactions initiated with pure precatalysts and precatalysts generated in situ from [Pd2(dba)3] and BINAP. This work reveals errors in both previous studies, and we describe our current state of understanding of the mechanism of this synthetically important transformation. 31P NMR spectroscopy shows that several palladium(0) species are present in the catalytic system when the catalyst is generated in situ from [Pd2(dba)3] and BINAP, and that at least two of these complexes generate catalytic intermediates. Further, these spectroscopic studies and accompanying kinetic data demonstrate that an apparent positive order in the concentration of amine during reactions of secondary amines is best attributed to catalyst decomposition. Kinetic studies with isolated precatalysts show that the rates of the catalytic reactions are independent of the identity and the concentration of amine, and studies with catalysts generated in situ show that the rates of these reactions are independent of the concentration of amine. Further, reactions catalyzed by [Pd(BINAP)2] with added BINAP are found to be first-order in bromoarene and inverse first-order in ligand, in contrast to previous work indicating zero-order kinetics in both. These data, as well as a correlation between the decay of bromobenzene in the catalytic reaction and the predicted decay of bromobenzene from rate constants of studies on stoichiometric oxidative addition, are consistent with a catalytic process in which oxidative addition of the bromoarene occurs to [Pd(BINAP)] prior to coordination of amine and in which [Pd(BINAP)2], which generates [Pd(BINAP)] by dissociation of BINAP, lies off the cycle. By this mechanism, the amine and base react with [Pd(BINAP)(Ar)(Br)] to form an arylpalladium amido complex, and reductive elimination from this amido complex forms the arylamine.