Palladium alkyl halides

Keywords Cross-coupling Homogeneous catalysis Palladium Alkyl halides... 

Substitution at the Carbon—Chlorine Bond. Vinyl chloride is generally considered inert to nucleophilic replacement compared to other alkyl halides. However, the chlorine atom can be exchanged under nucleophilic conditions in the presence of palladium [7440-05-3] Pd, and certain other metal chlorides and salts. Vinyl alcoholates, esters, and ethers can be readily produced from these reactions. 

Hardacre et al. have developed a procedure for the synthesis of deuterated imidazoles and imidazolium salts [65]. The procedure involves the platinum- or palladium-catalyzed deuterium exchange of 1-methyl-d -imidazole with D2O to give 1-methylimidazole-d , followed by treatment with a deuterated alkyl halide. 

A better method for preparing primary amines is to use the azide synthesis, in which azjde ion, N3, is used for SN2 reaction with a primary or secondary alkyl halide to give an alkyl azide, RN3. Because alkyl azides are not nucleophilic, overalkylation can t occur. Subsequent reduction of the alkyl azide, either by catalytic hydrogenation over a palladium catalyst or by reaction with LiAlK4. then leads to the desired primary amine. Although the method works well, low-molecular-weight alkyl azides are explosive and must be handled carefully. 

Although, as has already been mentioned, under matrix conditions between 10 and 77 K, there is no oxidative addition of a chloroolefin to nickel or palladium atoms (141), it is evident that this is simply a function of reaction and processing conditions, as it has been shown (68) that oxidative addition to C-C or C-H bonds by nickel atoms leads to pseudocomplexes having Ni C H ratios of 2-5 1 2. Klabunde and co-workers investigated the oxidative addition-reactions of palladium atoms with alkyl halides (73) and benzyl chlorides (74). 

Alkyl halides or alkyl sulfates, treated with the salts of sulfinic acids, give sulfones. A palladium catalyzed reaction with a chiral complexing agent led to sulfones with modest asymmetric induction. Alkyl sulfinates (R SO—OR) may be side products. Sulfonic acids themselves can be used, if DBU (p. 1337) is... 

Haloalkynes (R—C=C—X) react with ArSnBu3 and Cul to give R—C= C—Ar. Acetylene reacts with two equivalents of iodobenzene, in the presence of a palladium catalyst and Cul, to give 1,2-diphenylethyne. 1-Trialkylsilyl alkynes react with 1-haloalkynes, in the presence of a CuCl catalyst, to give diynes and with aryl triflates to give 1-aryl alkynes. Alkynes couple with alkyl halides in the presence of Sml2/Sm. Alkynes react with hypervalent iodine compounds " and with reactive alkanes such as adamantane in the presence of AIBN. ... 

It is possible to replace one isocyanide by triphenylphosphine, or to replace two isocyanides with diphos, giving phosphine analogues of these complexes. These species are not available from analogous reactions of phosphine-palladium(O) and (II) complexes. Reactions with active alkyl halides proceeds with oxidation nitric oxide also oxidizes these complexes. [Eqs. (31, 32)]. 

As reported in Scheme 1 the process involves a series of steps. The alkylpalladium species 1 forms through oxidative addition of the aromatic iodide to palladium(O) followed by noibomene insertion (4-7). The ready generation of complex 2 (8-11) from 1 is due to the unfavourable stereochemistry preventing P-hydrogen elimination from 1 (12). Complex 2 further reacts with alkyl halides RX to form palladium(IV) complex 3 (13-15). Migration of the R group to the... 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

Development of new methodologies for formation of carbon-carbon bonds has been one of the major tasks in organic chemistry. Obviously, organometallic compounds, particularly zinc derivatives, have found great use in such reactions. During the past several years, there have been several significant reports of nickel- and palladium-catalyzed reactions of dialkylzincs and alkylzinc halides with alkyl halides of diverse structure. A detailed account of most of these studies can be found in a recent review by Knochel et al,246... 

Several examples have been reported of the use of palladium-mediated oxidation reactions of alcohols and alkyl halides. Palladium(II) acetate in the presence of iodobenzene converts primary and secondary alcohols into carbonyl compounds under solid-liquid two-phase conditions [20], However, other than there being no further oxidation to carboxylic acids, the procedure has little to commend it over other methods. It is relatively slow with reaction times in the order of 2 days needed to achieve yields of 55-100%. 

Concurrent with acetic anhydride formation is the reduction of the metal-acyl species selectively to acetaldehyde. Unlike many other soluble metal catalysts (e.g. Co, Ru), no further reduction of the aldehyde to ethanol occurs. The mechanism of acetaldehyde formation in this process is likely identical to the conversion of alkyl halides to aldehydes with one additional carbon catalyzed by palladium (equation 14) (18). This reaction occurs with CO/H2 utilizing Pd(PPh )2Cl2 as a catalyst precursor. The suggested catalytic species is (PPh3)2 Pd(CO) (18). This reaction is likely occurring in the reductive carbonylation of methyl acetate, with methyl iodide (i.e. RX) being continuously generated. 

Two metal halides have been found to react with olefins by what appears to be insertion reaction. Palladium chloride and mercury chloride both will add to olefins. The palladium alkyls canot be isolated, but they go on to products which can be accounted for by an initial addition. 

Recently, this reaction has been extensively studied since it is currently the only method to couple aryl Grignard reagents with secondary alkyl halides Indeed, secondary aUtyl halides do not react under palladium or nickel catalysis . On the other hand, let us recall that the coupling of secondary alkyl Grignard reagents with aryl halides leads to poor results (see above). 

Recently, Fu and coworkers have shown that secondary alkyl halides do not react under palladium catalysis since the oxidative addition is too slow. They have demonstrated that this lack of reactivity is mainly due to steric effects. Under iron catalysis, the coupling reaction is clearly less sensitive to such steric influences since cyclic and acyclic secondary alkyl bromides were used successfully. Such a difference could be explained by the mechanism proposed by Cahiez and coworkers (Figure 2). Contrary to Pd°, which reacts with alkyl halides according to a concerted oxidative addition mechanism, the iron-catalyzed reaction could involve a two-step monoelectronic transfer. 

Arylzinc species prepared via the sacrificial anode process and from aryl halides in the presence of a nickel 2,2 -bipyridine, as already reported in Section . .1, were found totally unreactive towards common electrophiles such as aldehydes, carboxylic anhydrides or activated alkyl halides. However, they react with some electrophiles when they are activated by the presence of a catalytic amount of copper salts (10 mol% Cul) together with tetramethylethylene diamine (1MEDA) as described by Knochel and Singer on the ArZnX—CuCN metal exchange47 or when the reaction is catalyzed by palladium complex. 

Other Alkyl Ethers. Sucrose has been selectively etherified by electrochemical means to generate a sucrose anion followed by reaction with an alkyl halide (21,22). The benzylation of sucrose using this technique gives 2-O-benzyl- (49%), T-O-benzyl- (41%), and 3 -O-benzyl- (10%) sucrose (22). The benzylation of sucrose with benzyl bromide and silver oxide in DMF also produces the 2-O-benzyl ether as the principal product, but smaller proportions of T- and 3 -ethers (23). Octadienyl ether derivatives of sucrose, intermediates for polymers, have been prepared by a palladium-catalyzed telomerization reaction with butadiene in 2-propanol—water (24). 

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