Kumada-Corriu Reactions

Aryidehalogenation - Kumada-Corriu Reaction using Ni(ll)-Phosphine Catalysis... 

Drivers for Performing Kumada-Corriu Reactions in Micro Reactors... 

Beneficial Micro Reactor Properties for Kumada-Corriu Reactions... 

Kumada-Corriu Reactions Investigated in Micro Reactors Organic synthesis 47 [OS 47] Reaction between 4-bromoanisole and phenylmagnesium bromide [2]... 

In a Kumada-Corriu reaction, an aryl halide is oxidatively coupled with a homogeneous nickel(ll)-phosphine catalyst [2], This species reacts with a Grignard reagent to give biaryl or alkylaryl compounds. Later, palladium-phosphine complexes were also successfully applied. By this means, stereospecific transformations were achieved. 

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. 

In another development, it was shown that simple Ni(II) or Ni(0) precursors (e.g. NiCb, Ni(acac)2, Ni(COD)2, etc.) can catalyze the coupling of primary alkyl halides with Grignard reagents (Kumada-Corriu reaction). This otherwise challenging coupling of two sp -C centers is facilitated by the presence of various 1,3-butadienes this feature allows even the normally unreactive aUcyl chlorides to be coupled in very good yields and low catalyst loadings... 

HasweU, S.J., B. O Sullivan, and P. Styring, Kumada-Corriu reactions in a pressure-driven microflow reactor. Lab on a Chip, 2001,1 164—166. 

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]. 

Fiirstner and co-workers reported an iron-catalysed Kumada-Corriu reaction for the direct attachment of the octyl side chain [106]. 

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