Coupling reactions organomagnesium reagents

Aryl and vinyl haiides can be coupled in reactions catalyzed by palladium or nickel complexes bearing phosphine ligands [253], Allylic derivatives that are precursors of tt-allyl palladium complexes can also be coupled with organomagnesium reagents. Asymmetry can be induced by using chiral phosphines as ligands. 

Since chloro substituents in the benzenoid pyrimidine 5-position will not normally react with a stannane, the reaction between 2,5-dichloropyrimidine and styryltributylstannane is specific for the activated 2-position 5-bromo-2-chloropyrimidine is coupled with selective substitution of bromine in the 5-position (108). The 2-chlorine can subsequently be substituted [89ACSA(B)62]. In reactions of 2,4-dichloropyrimidine with /3-styryl- or phenyltributylstannane the carbosubstituent is selectively introduced into the 4-position (110) [89ACSA(B)62]. The same regioselectiv-ity is observed for Ni-catalyzed coupling with organomagnesium reagents (see below), and the regioselectivity corresponds to the relative reactivity... 

Organomagnesium reagents, which can serve as the nucleophiles in the Kumada coupling, are easy to make and many of them are commercially available. Even though some Kumada reactions can be run at room or lower temperature, many functional groups are not tolerant of Grignard reagents. Nonetheless, in the synthesis of thienylbenzoic acid 24, the carboxylic acid moiety did survive the reaction conditions [25],... 

P. Knochel, I. Sapountzis and N. Gommermann, Carbon-carbon bond-forming reactions mediated by organomagnesium reagents , in Metal-Catalyzed Cross-Coupling Reactions (Eds. A. de Meijere and E. Diederich), 2nd edn., Wiley-VCH, 2004, pp. 619-670. 

The transition metal catalyzed carbon-carbon bond formation between organomagnesium reagents and aryl (vinyl) halides has been one of the pioneering entries into cross-coupling chemistry. The reaction has been widely utilized since than in azine chemistry,22 with the limitation that the functional group tolerance of Grignard reagents is only moderate. Here only some of the more recent developments will be mentioned. 

The coupling of Grignard reagents with alkyl, vinyl or aryl halides under Ni-catalysis provides an economic transformation, but the reaction is limited to halide partners that do not react with organomagnesium compounds. One example is in the industrial-scale production of styrene derivatives, and the Kumada Coupling is the method of choice for the low-cost synthesis of unsymmetrical biaryls. 

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