Nickel catalysis reductive coupling

Keywords Allylation Carbonyl compound Dienes Homoallylation Nickel catalysis Reductive coupling... 

Although the titanium-based methods are typically stoichiometric, catalytic turnover was achieved in one isolated example with trialkoxysilane reducing agents with titanocene catalysts (Scheme 28) [74], This example (as part of a broader study of enal cyclizations [74,75]) was indeed the first process to demonstrate catalysis in a silane-based aldehyde/alkyne reductive coupling and provided important guidance in the development of the nickel-catalyzed processes that are generally more tolerant of functionality and broader in scope. 

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 transition-metal-catalysed exchange of halogen atoms may also be viewed as a heteroatom coupling reaction. It is particularly useful for the conversion of the cheaper and more available chloro compounds to the more reactive iodo compounds. Nickel catalysis may be used (Scheme 2.185). Cyanide can also be coupled (Scheme 2.186). The use of hydride sources, such as formate or tri-n-butyltinhydride is a method of removing functionality (Scheme 2.187). The mechanism of formate reduction is illustrated in Scheme 5.50. 

Other metals can catalyze Heck-type reactions, although none thus far match the versatility of palladium. Copper salts have been shown to mediate the arylation of olefins, however this reaction most probably differs from the Heck mechanistically. Likewise, complexes of platinum(II), cobalt(I), rhodium(I) and iridium(I) have all been employed in analogous arylation chemistry, although often with disappointing results. Perhaps the most useful alternative is the application of nickel catalysis. Unfortunately, due to the persistence of the nickel(II) hydride complex in the catalytic cycle, the employment of a stoichiometric reductant, such as zinc dust is necessary, however the nickel-catalyzed Heck reaction does offer one distinct advantage. Unlike its palladium counterpart, it is possible to use aliphatic halides. For example, cyclohexyl bromide (108) was coupled to styrene to yield product 110. 

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