Oxidation electrophilic substrates

Pyridine is a jt-electron-deficient heterocycle. Due to the electronegativity of the nitrogen atom, the a and y positions bear a partial positive charge, making the C(2), C(4), and C(6) positions prone to nucleophilic attacks. A similar trend occurs in the context of palladium chemistry. The a and y positions of halopyridines are more susceptible to the oxidative addition to Pd(0) relative to simple carbocyclic aryl halides. Even a- and y-chloropyridines are viable electrophilic substrates for Pd-catalyzed reactions under standard conditions. 

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

Early studies of these complexes focused primarily on the investigation of their oxygen-atom-transfer reactivity. Relatively little success was achieved, however. The peroxo fragments in these complexes exhibit nucleophilic character, and, therefore, they are generally ineffective oxidants for reactions with synthetically interesting electron-rich substrates such as alkenes and sulfides. Most of the known reactivity involves electrophilic substrates that, in many cases, insert into the Pd-0 bond of peroxopalladium(II) species (Fig. 4) [105,118]. 

Reactions with electrophilic substrates. Oxygen peroxide formed during the development of the early products and hydroperoxides can attack electrophilic substrates according to an ionic, nonradical reaction. In this way, carbon-carbon double bonds can be transformed into epoxides and tertiary amines into N-oxides. These are cooxidations with an ionic mechanism. 

Homolytic catalysis is observed with both organometallic and coordination complexes. It is involved in a wide variety of metal-mediated transformations, often in competition with electrophilic or nucleophilic catalysis [11], For example, many metal-catalyzed oxidations involve substrate activation by homolytic catalysis (Eq. 5) [12], Similarly, oxidative additions (Eq. 6) and dioxygen activation (Eq. 7) can proceed via two-step homolytic mechanisms. 

Catechols and Hydroquinones. Just as quinones are ideal examples of electrophilic substrates, their fully reduced form (catechols and hydroquinones) illustrates the electrochemical oxidation of aromatic nucleophilic substrates (Lewis bases). Figure 12.3a, b illustrates the oxidation of 3,5-di+m-butyl-catechol (DTBCH2) via an irreversible two-electron process (ECEC) to give the o-quinone (DTBQ) 12... 

The nucleophilicity of oxyanions (YO ) is directly related to their oxidation potentials (E° bJb., Table 15) and the bond energies of their products (YO R) with electrophilic substrates (RX) (equation 183). 

Summary Decamethylsilicocene (1), the first Si(II) compound stable under ordinary conditions [1], is a h5 ercoordinated nucleophilic silylene, which reacts preferentially with electrophilic substrates [2], In the reaction of 1 with the electrophilic heterocumulenes CO2, COS and RNCS (R = Me, Ph), double bond species of the type Cp 2Si=X (X = O, S) are formed, which are stabilized via different routes to the silaheterocycles I-IV [3], Multistep rearrangement processes are postulated to explain the formation of the dithiasiletane derivatives V and VI in the reaction of 1 with CS2. A surprising polycyclic silaheterocycle VII is obtained in the reaction of 1 with hexafluorobutyne. With HMn(CO)s 1 reacts to the dimanganese-substituted silane VIII. In all reactions, the lone pair at silicon is involved, an r) -ri - rearrangement of the Cp ligands take place, and the formal oxidation state at Si changes to +4 in the final products. 

Table 8-1 Redox Potentials for the Single-Electron (a) Oxidation of HO and Other Oxy Anion Bases and (b) Reduction of Electrophilic Substrates in Water and in Acetonitrile... 

Electrophilic activation of coordinated peroxides can be achieved by protonation, which typically yields end-on coordinated hydroperoxides.16 For example, the well-defined hydroperoxo complexes of rhodium and chromium efficiently oxidize inorganic substrates such as halide anions these reactions are acid catalyzed.16 Hydroperoxo intermediates were implicated in some enzymatic oxidations, such as hydroxylation catalyzed by cytochrome P450 (Figure 4.32). Although significant... 

Table 15 Redox potentials for the single-electron (a) oxidation of HO and other oxyanion bases and (b) reduction of electrophilic substrates in water and in acetonitrile...

There are two main classes of molecules (substrates) that can perform oxidative additions to metal centers non-electrophilic and electrophilic. Oxidative addition reactions with either class of substrates are favored by metal complexes that are more electron rich. Common non-electrophilic substrates are H2, Si-H bonds, P-H bonds, S-H bonds, B-H bonds, N-H bonds, S-S bonds, C-H bonds, alkenes, and alkynes. An important criterion for these non-electrophillic substrates is that they require a sterically accessible open coordination site on the metal (16e configuration or lower) onto which they need to pre-coordinate before initiating the oxidative addition to the metal center. For these substrates, both ligand atoms typically become cisoidally coordinated to the metal center after the oxidative addition as anionic (T-donors (subsequent ligand rearrangements, of course can occur). H2 is the most important and common for catalysis and a well-studied reaction is shown in Equation (5). 

Electrophilic ligands differ from the non-electrophilic substrates in that they do not necessarily need a low-lying empty orbital on the metal center in order to pre-coordinate necessary for oxidative addition. Although the Ir complex shown in Figure 2 does have an empty orbital, this is not believed to play an important role in the oxidative addition reaction. An example with an 18e complex is shown in Equation (6). 

The Stille reactions of aryl chlorides, as the least reactive electrophilic substrates can be successfully performed by applying a palladium-complex of electron-rich and sterically encumbered Pt-Bus as Pd(0)-stabilizing ligand [78]. The latter increases the electron-density at palladium metallic centre and thus facilitates the oxidative addition step of unreactive electron-rich aryl chlorides to the Pd(Pt-Bu3)2- For instance, even 4-chloroanisole (76), among the least reactive chlorides, was reacted with phenyltri-n-butylstannane (184) to give 4-methoxybiphenyl (78) in 94% yield [78], respectively,... 

---