Halides, alkyl coupling with Grignard reagents

Alkanes, RH (Sec. 7.7) (Sec. 10.7) (Sec. 10.8) (Sec. 19.9) from alkenes by catalytic hydrogenation from alkyl halides by protonolysis of Grignard reagents from alkyl halides by coupling with Gilman reagents from ketones and aldehydes by Wolff-Kishner reaction... 

Tosylates and other sulfonates and sulfates couple with Grignard reagents, most often those prepared from aryl or benzylic halides.Alkyl sulfates and sulfonates generally make better substrates in reactions with Grignard reagents than the corresponding halides (10-57). The method is useful for primary and secondary R. 

Coupling of alkyl halides with Na, supplanted by the coupling of alkyl halides or sulfonates with Grignard reagents or RLi in the presence of Cu(l) salts (see 1st edition). 

Sulfonyl chlorides are totally defunctionalized (with loss of SO2 also) during coupling with Grignard reagents. Alkenylmagnesium bromides and alkyl halides (bromides and iodides) are coupled in the presence of FeCls and TMEDA, whereas for the formation of ArMgBr and RX a complex derived from FeCls and 1 has been identified. ... 

Recently, this reaction has been extensively studied since it is currently the only method to couple aryl Grignard reagents with secondary alkyl halides Indeed, secondary aUtyl halides do not react under palladium or nickel catalysis . On the other hand, let us recall that the coupling of secondary alkyl Grignard reagents with aryl halides leads to poor results (see above). 

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. 

Fig. 50 Cobalt-catalyzed cross-coupling of alkyl halides with Grignard reagents...

C. Cross Coupling of Grignard Reagents and Alkyl Halides with Copper(I) CatalystiT Copper(I) specifically catalyzes the cross coupling (Equation 35) between Grignard reagents and alkyl bromides when carried out in THF solutions at 0°C or lower.(39)... 

D. Homo-Coupling with Silver(I). Silver is an effective catalyst for the coupling of Grignard reagents and alkyl halides, and it is especially useful when both alkyl groups are the same.(43) When different alkyl groups are employed, a mixture of three coupled products is obtained. Disproportionation becomes increasingly important with secondary and tertiary... 

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... 

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