Nickel catalysis alkylation

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). 

Nickel catalysis in the electrosynthesis of aryl- and heteroarylzinc reagents, and in the electrochemical Reformatsky and allylation reactions using alkyl chlorides... 

For this specific task, ionic liquids containing aluminum alkyls proved to be unsuitable, due to their strong isomerization activity [241]. Since, mechanistically, only the linkage of two Tbutene molecules can lead to the formation of hnear octenes, isomerization activity of the solvent inhibits the formation of the desired product. Therefore, slightly acidic chloroaluminate melts that enable selective nickel catalysis without the addition of aluminum alkyls have been developed [239]. It was found that an acidic chloroaluminate ionic liquid buffered with small amounts of weak organic bases provides a solvent which allows a selective, biphasic reaction using nickel [(H-COD)Ni(hfacac)]. 

Recently it has proved possible to cross-couple alkylzinc halides with primary alkyl haUdes. This can be achieved under nickel catalysis in the presence of tetra-butylanunonium iodide and4-lluorostyrene (1.141). As expected with this chemistry, the reaction tolerates a range of functional groups such as the presence of ketones and carboxyUc esters. 

In 1998, Knochel reported that, in the presence of 4-trifluoromethylstyrene, [Ni(acac)2] efficiently catalyzed cross-couplings between polyfunctional arylzinc derivatives and alkyl halides possessing P-hydrogens (Equation 5.15). While the alkyl halides were limited to primary alkyl iodides, the scope of nickel catalysis was significantly expanded. The role of the electron-deficient olefin, 4-trifluoromethylstyrene, was proposed to accelerate the reductive elimination step by decreasing the electron density at the nickel center of an (alkyl) (aryl)nickel intermediate [18]. 

The same group reported an extension of the direct alkylation of (benz)oxazoles with various alkyl bromides and chlorides by using the stronger base lithium tert-butoxide (Scheme 19.23) [38]. 5-Aryloxazoles containing electronically diverse substituents such as CFj and OMe were also alkylated successfully. Various linear alkyl chains were introduced, such as phenylpropyl, citronellyl, or octyl, affording interesting lipophilic molecules. The optimized reaction conditions failed to apply to benzothiazoles, and the authors had to turn their attention to nickel catalysis to achieve the corresponding alkylation (Section 19.2.3). Experiments were run to understand the reaction mechanism that presumably involves Sj 2-type oxidative addition of the alkyl halide to palladium(O) followed by transmetallation by the in situ-lithiated (benz)oxazole (Scheme 19.24). 

In addition to iridium and cobalt catalysis, and following the work initiated by Cavell et al. [138] on the alkylation of azolium salts, nickel-catalyzed alkylations of various heteroarenes (i.e., indoles [139], benzimidazoles [139], benzothiazoles [139], benzoxazoles [139], 1,3,4-oxadiazoles [140]) with olefins have been reported (Scheme 19.95 and Scheme 19.96). These reactions proved complementary to other methods because they proceeded with the Markovnikov regioselectivity with respect to the olefin. 

Salt-activated Fe(TMP)2-2MgCl2-4LiCl was successfully used in THF at room temperature to convert activated 1,3- and 1,4-disubstituted arenes into the corresponding diaryliron(It) species. The latter were cross-coupled under nickel catalysis with alkyl iodides and bromides or even benzyl chloride. The reaction tolerates a large range of functional groups (Table 27.9) [22]. 

Suzuki Cross-coupling Reactions. The formation of sp -sp carbon-carbon bonds is possible through the coupling of primary and secondary alkyl iodides and bromides with unsaturated boronic acids, under nickel catalysis using bathophenanthroline as ligand. As a result, an important variety of compounds bearing different functionalities can be coupled under mild conditions with good yields (eq 6). ... 

Flowever, information concerning the characteristics of these systems under the conditions of a continuous process is still very limited. From a practical point of view, the concept of ionic liquid multiphasic catalysis can be applicable only if the resultant catalytic lifetimes and the elution losses of catalytic components into the organic or extractant layer containing products are within commercially acceptable ranges. To illustrate these points, two examples of applications mn on continuous pilot operation are described (i) biphasic dimerization of olefins catalyzed by nickel complexes in chloroaluminates, and (ii) biphasic alkylation of aromatic hydrocarbons with olefins and light olefin alkylation with isobutane, catalyzed by acidic chloroaluminates. 

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