Intramolecular processes oxidative addition

Hartwig has reported an intramolecular/intermolecular process affording the 3-aryloxindoles 105 (Scheme 32).115 The intermolecular arylation of acetanilide derivative 104 is slower than the intramolecular arylation to form the oxindole. Thus, the overall transformation starts with cyclization followed by intermolecular arylation of indole. In order to slow down the intermolecular process and speed up the intramolecular reaction, chloroarene and bromine-substituted acetanilide precursors are used according to their respective reactivity with palladium(O) in the oxidative addition process. 

Oxidative additions involving C-H bond breaking have recently been the topic of an extensive study, usually referred to as C-H activation the idea is that the M-H and M-hydrocarbyl bonds formed will be much more prone to functionalization than the unreactive C-H bond. Intramolecular oxidative additions of C-H bonds have been known for quite some time see Figure 2.15. This process is named orthometallation or cyclometallation. It occurs frequently in metal complexes, and is not restricted to "ortho" protons. It is referred to as cyclometallation and is often followed by elimination of HX, while the metal returns to its initial (lower) oxidation state. 

There is ample evidence that the reductive elimination of alkanes (and the reverse) is a not single-step process, but involves a o-alkane complex as the intermediate. Thus, looking at the kinetics, reductive elimination and oxidative addition do not correspond to the elementary steps. These terms were introduced at a point in time when o-alkane complexes were unknown, and therefore new terms have been introduced by Jones to describe the mechanism and the kinetics of the reaction [5], The reaction of the o-alkane complex to the hydride-alkyl metal complex is called reductive cleavage and its reverse is called oxidative coupling. The second part of the scheme involves the association of alkane and metal and the dissociation of the o-alkane complex to unsaturated metal and free alkane. The intermediacy of o-alkane complexes can be seen for instance from the intramolecular exchange of isotopes in D-M-CH3 to the more stable H-M-CH2D prior to loss of CH3D. 

Perutz and coworkers [180] have used 2D EXSY to study the dynamic behavior of RhCp(PMe3)(q -naphthalene), 109, which is thought to be a model intermediate for the oxidative addition of arenes to a metal center. In this complex, there are two processes taking place. The first involves an equilibrium between the -naphthalene complex, 109, and the naphthyl hydride complex, 110. The second process involves an intramolecular [l,3]-shift which moves the coordination site of the naphthalene ring from one side of the ring to the other (Scheme 1.12). 

The ability to harness alkynes as effective precursors of reactive metal vinylidenes in catalysis depends on rapid alkyne-to-vinylidene interconversion [1]. This process has been studied experimentally and computationally for [MC1(PR3)2] (M = Rh, Ir, Scheme 9.1) [2]. Starting from the 7t-alkyne complex 1, oxidative addition is proposed to give a transient hydridoacetylide complex (3) vhich can undergo intramolecular 1,3-H-shift to provide a vinylidene complex (S). Main-group atoms presumably migrate via a similar mechanism. For iridium, intermediates of type 3 have been directly observed [3]. Section 9.3 describes the use of an alternate alkylative approach for the formation of rhodium vinylidene intermediates bearing two carbon-substituents (alkenylidenes). 

Acylpalladium intermediates can be involved in intramolecular processes leading to the formation of carbo- or heterocycles. In this chapter we discuss the cyclizations via the attack of acylpalladium intemediates at carbon centers and formation of new G-G bonds. The basic scheme (Scheme 7) of such processes includes the oxidative addition of Pd(0) to G(j )-X bonds (X = halogen or triflate), migratory insertion of GO, and subsequent intramolecular addition of acylpalladium intermediate to double or triple bonds to yield cyclic ketones. 

Sulfine complexes of platinum(II) can be formed by oxidative addition to Pt(PPh3)3. The initial step involves the formation of an rj2-CS complex which undergoes intramolecular oxidative addition of a C—S bond (equation 542).1869 Use of Pt(cod)2 and PCy3 gives the tricyclohexylphosphine analogue.1870 The reaction gives two stereoisomers.1871 The coordination stabilization of sulfines allows their synthesis in the coordination sphere of platinum, but the cyclic process is not very efficient.1872... 

The mechanisms proposed for these reactions are all quite analogous, and only the intramolecular cases will be considered in detail (Scheme 5). Oxidative addition by Pd° into the allylic C—O bond of the allyl 0-ketocaiboxylate produces an allylpalladium caxboxylate. This species then undergoes decarboxylation to yield an allylpalladium enolate (oxa-ir-allyl), which subsequently eliminates a 0-H to form the enone and provide an allyl-Pd-H. Reductive elimination from the allyl-Pd-H yields propene and returns Pd to its zero oxidation state. A similar mechanism can be imagined for the alkenyl allylcarbonate. Oxidative addition by the Pd° forms an allylpalladium carbonate, which decarboxylates again to give an allylpalladium enolate (oxa-ir-allyl). 0-Hydride elimination and reductive elimination complete the process. The intermolecular cases derive the same allylpalladium enolate intermediates, only now as the result of bimolecular processes. 

Metallacyclobutene complexes of both early and late transition metals can, in some cases, be prepared by intramolecular 7-hydrogen elimination, although the intimate mechanism of the reaction varies across the transition series. For low-valent late metals, the reaction is generally assumed to proceed via the oxidative addition of an accessible 7-C-H bond (Scheme 28, path A), but for early metals and, presumably, any metal in a relatively high oxidation state, a concerted cr-bond metathesis is considered most probable (path B). In this process, the 7-C-H bond interacts directly with an M-X fragment (typically a second hydrocarbyl residue) to produce the metallacycle with the extrusion of H-X (i.e., a hydrocarbon). Either sp3- or spz-hybridized C-H bonds can participate in the 7-hydrogen elimination. 

Oxidative addition of the silane to the metal is fast and reversible 30 therefore unless the pentacoordinated silane drastically slows down the oxidative addition process, pentacoordination will not alter the rate of the reaction at this stage of the cycle. The increased reactivity of le may be explained by the attack of the alcohol on the pentacoordinated silane that would form after oxidative addition (Figure 9A). The rate of the alcohol addition is increased by the higher reactivity of the pentacoordinated silicon center. This may explain the slower reactivity for those alkoxysilanes that cannot form this intramolecular coordination complex due to the absence of a nearby Lewis basic atom. We had observed during the comparison of aliphatic alcohol to benzyl alcohol that the nucleophilicity of the alcohols has an effect on the rate of the reaction. This is evidence that the alcohol and the silane are involved in the rate-determining step with 10 % Pd/C catalytic system. 

On the basis of these findings, a combination of this intramolecular crosscoupling with an initial intermolecular Michael addition was reported by Singer in order to afford cyanobenzofulvene acetal 85 which was an intermediate of the synthesis of a benzazepine [81]. Thus, Michael addition of 2-halophenylacetonitrile derivatives of 86 to ethoxy acrylate performed in the presence of a large excess of base leads to the corresponding conjugated allylic anion 87. The crucial issue in this process is the oxidative addition of the palladium to the electron-rich arene. This problem was solved... 

Orthometallation of triarylphosphine and triarylphosphite at mthenium has long been knovm as intramolecular C-H bond activation in ruthenium chemistry [2], but did not receive attention from organic chemists. In 1965, Chatt and Davidson documented that a Ru(0) complex, which was formed by two-electron reduction of Ru(II) by use of sodium naphthalene is capable of reversible cleavage of sp C-H bonds of naphthalene by oxidative addition/reductive elimination processes (Scheme 14.1) [3]. 

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