Transition-Metal-Catalyzed Cross-Coupling Reactions of Organozinc Reagents

Transition-Metal-Catalyzed Cross-Coupling Reactions of Organozinc Reagents 

The use of palladium, and to a minor extent nickel, catalysts (the Negishi cross-coupling cf. Chapter 3 of this book), is prevalent and stiU attracts most of the research interest. In recent years, however, some other variants involving, for instance, cobalt or iron catalysis have emerged. 

In general terms, cross-couplings involving either C(sp )-nucleophiles [124] or C(sp )-electrophiles [125, 126] with fi-hydrogens are more challenging, as byproduct formation associated with fi-hydride eUmination of the intermediately formed alkyl transition metal complexes can potentially hamper the reaction. 

Transition-metal-catalyzed cross-coupling reactions of C(sp )-organozincs have been vastly utilized in many areas of organic synthesis. Many procedures are weU established in the synthetic toolbox, but a number of challenges stiU exist 

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The introduction of a polyfluorinated chain is not so easy as that of an alkyl chain. Transition metal catalyzed cross-coupling of Grignard reagents and organozinc compounds are inefficient in the synthesis of polyfluorinated 3-alkylthiophene. The copper-catalyzed perfluoroalkylation results in the formation of 2-and 3-substituted thiophenes, which are difficult to separate from each other. The reaction of fluorinated alkylmagnesium iodide with 3-formylthiophene, follwed by reduction with lithium aluminum hydride, gave (22) in an overall yield of 40% [27]. 

Organozinc compounds tolerate a broad range of functional groups. Cross-coupling reactions between organozinc reagents and electrophiles such as orgauic hahdes are catalyzed by transition metal complexes. However, examples for the selective... 

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