Nucleophilic attack oxidative addition reactions

In 1,3-benzazoIes (benzoxazoles, benzothiazoies, benzoselenazoles) the heteroatom that is not nitrogen shows very low nucleophilicity and does not serve as a reaction center in electrophilic addition and oxidation-addition reactions. By contrast the tellurium atom in benzotellurazoles is quite susceptible to attack by electrophiles and oxidants. 

A number of intimate mechanisms have been found for the oxidative addition reaction, including Sn2 nucleophilic attack, as in the addition of Mel to Rh(I) (Section 4.2.5). 

Alkyl halides that do not readily undergo nucleophilic attack may oxidatively add to a metal by radical mechanisms. Oxidative addition reactions that occur by radical mechanisms show loss of stereochemistry, nomeproducible rates, inhibition by radical inhibitors, and acceleration by O2 or light. Reactions of lr(Cl)(CO)(PMe3)2 with methyl and benzyl halides showed no indication of radical behavior, but other saturated alkyl halides, vinyl, and aryl halides showed characteristics consistent with a radical-chain pathway. 

In support of this suggestion, when [Rh2(CO)2( r-SP AN-POP) (p-Cl)2] was used as a catalyst precursor, the catalytic reaction rate was four times higher than when a 1 1 (molar) diphosphine Rh ratio was used. In a subsequent computational investigation, the oxidative addition reactions of Mel with di-rhodium complexes, [Rh(CO)(PR3)( r-Cl)]2 (R = H, Me) and that with mononuclear [Rh(CO)(PH3)2Cl] and [Rh(CO)2I2] were compared on the basis of DFT calculations [96]. Calculated activation parameters for nucleophilic attack by rhodium on Mel showed good agreement with experimental results. 

In the dimerization reaction of butadiene catalyzed by palladium complexes, nucleophiles (YH), such as amines, alcohols, phenols, carboxylic acids 41 4S>, and active methylene compounds 46) are introduced. This reaction can be explained by the attack of these nucleophiles on the jr-allylic complexes formed as intermediates-in the reactions. Takahashi, Shibano, and Hagihara confirmed by using deuterium that the hydrogen of YH migrates to C6 of the dimeric product, probably via the oxidative addition reactions of YH to the palladium species 42). 

The second direct reaction pathway, one-electron reduction of a target by nitric oxide, could occur only if the target was itself a strong oxidant, since nitric oxide does not readily give up its unpaired electron. Oxidation of nitric oxide would result in the formation of NO, which would rapidly nitrosate nucleophiles such as amines, sulfhydryls, or aromatics. In fact, the best one-electron oxidants would be radicals such as -NOi or hydroxyl radical or even ONOO itself. In such cases the net effect would be nitric oxide addition reactions (nitrosations), regardless of whether the mechanism is considered to be transfer of an electron from nitric oxide followed by attack of NO or simple radical-radical combination. Thus, under most conditions, one-electron reduction of a target by nitric oxide becomes a simple addition reaction. 

Rh(TTP) reacts with alkyl halides, acyl halides, aroyl halides, and sulfonyl halides, but it shows no evidence of reaction with molecular hydrogen. These observations further emphasize the fact that Rh(TTP) is essentially a nucleophile and it therefore reacts with those reagents RX that can oxidatively add by nucleophilic attack (34). Rh(TTP) does not react with H2, and H2 seems always to add to (P complexes via a concerted mechanism (35). It appears that Rh(TTP) has very little diradical character, i.e. it is not a good analog of a carbene (35). It is possible that this unreactivity may be associated with the stereochemistry of chelation by the macrocyclic ligand. Earlier studies on the oxidative addition reactions of Rh(I) complex with a tetraaza macrocycle revealed that the Rh(I) had strong nucleophilic properties but the activation of molecular H2 was not reported (36, 37). This possibility is supported by reports that dialkyl sulfide complexes of rhodium chloride catalyze the hydrogenation of olefins (38). 

The oxidative addition reactions to alkenes promoted or catalyzed by PdCl2(CH3CN)2 have been classified based on the nature of the attacking species. Oxygen nucleophiles such as water, alcohols and carboxylic acids undergo oxypalladation, while ammonia, amines and their derivatives are typical nucleophiles for aminopalladation. Carbopalladation with active methylene compounds is also discussed The palladium-catalyzed intramolecular hetero- and carbopalladation of olefins is extensively used as the ring-forming step in the synthesis of a variety of heterocyclic and carbocyclic systems, and representative examples are provided. 

Kinetic studies of the stoichiometric oxidative addition reactions" have shown that the reaction of Mel with [Ir(CO)2l2] is ca. 100 times faster than that with [Rh(CO)2l2], consistent with the different rate-determining steps found in the catalytic reactions of the two metals. It has also been found that oxidative addition to [Ir(CO)2l2] is ca. 100 times faster than to the neutral acetonitrile solvate, [Ir(CO)2(NCMe)I], demonstrating the benefit of an anionic complex for this step in the catalytic cycle. Theoretical studies " support an Sn2 mechanism for oxidative addition of Mel to [M(CO)2l2] - Nucleophilic attack by the metal center results in release of I from Mel via the transition state shown in Figure 4, to give the five-coordinate intermediate, [M(CO)2l2Me]. Geometrical features of the calculated transition state (e.g., deviation of the M-C-I angle from linearity) are dependent on the... 

Formation of a Tr-allylpalladium complex 29 takes place by the oxidative addition of allylic compounds, typically allylic esters, to Pd(0). The rr-allylpal-ladium complex is a resonance form of ir-allylpalladium and a coordinated tt-bond. TT-Allylpalladium complex formation involves inversion of stereochemistry, and the attack of the soft carbon nucleophile on the 7r-allylpalladium complex is also inversion, resulting in overall retention of the stereochemistry. On the other hand, the attack of hard carbon nucleophiles is retention, and hence Overall inversion takes place by the reaction of the hard carbon nucleophiles. 

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

The dependence of relative rates in radical addition reactions on the nucleophilicity of the attacking radical has also been demonstrated by Minisci and coworkers (Table 7)17. The evaluation of relative rate constants was in this case based on the product analysis in reactions, in which substituted alkyl radicals were first generated by oxidative decomposition of diacyl peroxides, then added to a mixture of two alkenes, one of them the diene. The final products were obtained by oxidation of the intermediate allyl radicals to cations which were trapped with methanol. The data for the acrylonitrile-butadiene... 

Attempts to employ allenes in palladium-catalyzed oxidations have so far given dimeric products via jr al lyI complexes of type 7i62.63. The fact that only very little 1,2-addition product is formed via nucleophilic attack on jral ly I complex 69 indicates that the kinetic chloropalladation intermediate is 70. Although formation of 70 is reversible, it is trapped by the excess of allene present in the catalytic reaction to give dimeric products. The only reported example of a selective intermolecular 1,2-addition to allenes is the carbonylation given in equation 31, which is a stoichiometric oxidation64. 

While the alkoxymetallation process has typically been affected by highly electrophilic metal salts, high-valent metal species generated by an oxidative addition have also been used to activate alkynes through the formation of 7r-complexes. In such cases, the metal-carbon emerging from the attack of an oxygen nucleophile may enter a reaction manifold that leads to an additional C-G bond formation rather than a simple protic quench. This approach, pioneered by Arcadi and Cacci, has proved to be a powerful strategy for the synthesis of structurally diverse substituted... 

Sn2 and SNAr Reactions In these reactions the metal atom attacks aliphatic or aromatic carbon bonded to X, respectively. A stronger nucleophilic metal as well as a better leaving group X (I>Br>Cl>F) facilitates, whereas steric hindrance in R slows these types of oxidative addition [193, 194]. SNAr reactions are favored by electron-withdrawing substituents Y in the case of the substrates 4-YQH4X [2], Sn2 [27, 29, 89, 117, 180, 181] and SNAr [31, 33, 62-67, 95, 100, 107-109] mechanisms have been suggested frequently for zerovalent d10 complexes such as [L M] (M = Ni, Pd, Pt L=tertiary phosphine =2,3,4). For example ... 

The Tsuji-Trost reaction is the palladium-catalyzed allylation of nucleophiles [110-113]. In an application to the formation of an A-glycosidic bond, the reaction of 2,3-unsaturated hexopyranoside 97 and imidazole afforded A-glycopyranoside 99 regiospecifically at the anomeric center with retention of configuration [114], Therefore, the oxidative addition of allylic substrate 97 to Pd(0) forms the rc-allyl complex 98 with inversion of configuration, then nucleophilic attack by imidazole proceeds with a second inversion of configuration to give 99. 

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. 

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