The Kumada-Corriu Reaction

Coupling reactions between alkyl Grignards and aryl halides are usually successful using nickel-phosphine catalysts however, if the aromatic halide has an alkoxy substituent this does not work very well and it is better to couple an aromatic Grignard with an alkyl halide as shown above. 

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The Kumada-Corriu reaction is characterized by mild conditions and clean conversions [2]. A disadvantage of previous Kumada-Corriu reactions was due to the use of homogeneous catalysts, with more difficult product separation. Recently, an unsymmetrical salen-type nickel(II) complex was synthesized with a phenol functionality that allows this compound to be linked to Merrifield resin polymer beads (see original citation in [2]). By this means, heterogeneously catalyzed Kumada-Corriu reactions have become possible. 

Other successful examples of catalysts containing NHC ligands are found in palladium- and nickel-catalyzed carbon-carbon bond formations. The catalyst development with these metals has focused in particular on Heck-type reactions, especially the Mizoroki-Heck reaction itself [Eq. (42)] and various cross coupling reactions [Eq. (43)], e.g., the Suzuki-Miyaura reaction ([M] = and the Kumada-Corriu reaction ([M] = MgBr). " Related reactions like the Sonogashira coupling [Eq. (44)]326-329 Buchwald-... 

For nickel(O) complexes prepared from Ni(r -cod)2 and an excess of the free NHC, it was shown that they exhibit outstanding catalytic activity in the Kumada-Corriu reaction at room temperature toward unreactive substrates like aryl chlorides and even aryl fluorides.Again, an essential element of these catalysts is the need for sterically demanding NHC ligands as observed for the palladium catalysts. 

Figure 3,95 Synthesis of a nickel(ll) phosphino functionalised imidazolium complex for use as catalyst in the Kumada-Corriu reaction.

When we go from palladium to nickel, we stay within group 10 and retain the square planar geometry common to most d -complexes. We do not need to concern ourselves with the synthesis and structure of nickel(II) pincer carbene complexes. They are analogous to the palladium(II) homologues. However, in their applications, the Kumada-Corriu reaction [291,292] takes a prominent place besides the Heck and Suzuki reactions encountered also with palladium. 

Coupling reactions that are included in this chapter are the Heck-Mizoroki reaction, the Suzuki-Miyaiu-a reaction, the Sonogashira reaction, the Kumada-Corriu reaction, the Negishi reaction, allylic substitution and arylation via CH-activation. 

Scheme 29 The Kumada-Corriu reaction in the production of line chemical intermediates...

Scheme 31 Use of the Kumada-Corriu reaction in the synthesis of Cinacalcet...

Ranbaxy has a patent application on the production of Cinacalcet hydrochloride 23 in which the Kumada-Corriu reaction is used. They use 5 mol% of Fe(acac)3 as catalyst in the reaction between vinyl chloride 136 and Grignard reagent 137, and the coupling product was isolated in 70% yield (Scheme 31) [88]. 

Although discovered and assessed in scope and limitation over a decade ago [68, 74], the aryl O-carbamate cross-coupling partner for the Kumada-Corriu reaction has not seen widespread application. This conceptual 1,2-dipole synthetic equivalent (Scheme 14.10) has been reasonably well tested using simple, not necessarily always aromatic, Grignard reagents and these have been compared with the... 

Consideration of quahtatively similar cross-coupling reactivity allows an extension of the Kumada-Corriu reaction to sulfonamide leaving groups and provides yet another 1,2-dipole synthetic equivalent (Scheme 14.15, Table 14.12). Successful... 

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