Aryl halides with Grignard reagents

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). 

Perfluoroaryl alkyl sulfides (e.g., 7) can be synthesized by the reaction of Grignard reagents with aryl halides in the presence of elemental sulfur. For example, allyl pentalluorophenyl sulfide (7) is obtained in excellent yield from bromopentafluorobenzene (5) and allyl bromide... 

On the other hand, for a series of [Pd(L-L)Me2] with L-L = dppp (bis(l,3-diphenylphosphino)propane), dppf, and dppr (l,l -bis(diphenylphosphino)ruthe-nocene), the fastest elimination was observed for the ligand with the largest bite angle [357, 358]. This effect on the reductive elimination was also found by Hayashi et al. [359] and van Leeuwen [360] in the palladium-catalyzed cross-coupling reaction of Grignard reagents with aryl halides. 

The need for a more efficient and a more versatile synthetic route to PPP was filled by Yamamoto et al. [50] in the late 1970s. Results indicating that transition metals or their complexes catalyze the coupling of Grignard reagents with aryl halides [51] were adapted... 

Coupling Grignard reagents with aryl halides ... 

Kharasch discovered that CuCl catalyzes the coupling of aryl Grignard reagents with aryl halides, and also the 1,4-addition of Grignard reagents to a,/3-unsaturated ketones. While the former has been called the Kharasch reaction , today the latter is much more important synthetic ally, and it should be named for... 

Scheme 29 Iron-catalyzed cross coupling reaction of aryl Grignard reagents with alkyl halides...

The perfluorohalogenomethylraercapto compound is formed in about 50% yield, the by-products being aryl halides from the Grignard reagent in 5-15% yield. It is assumed that the reaction follows an Sn2 mechanism with a cyclic intermediate state in analogy with the reaction of Grignard reagents with alkyl halides 98, 155), e.g.,... 

PHOSPHINE-NICKEL COMPLEX CATALYZED CROSSCOUPLING OF GRIGNARD REAGENTS WITH ARYL AND ALKENYL HALIDES 1,2-DIBUTYLBENZENE... 

In 1971, a year before the groups of Corriu and Kumada [5] independently reported the groundbreaking work on the topic of nickel-catalyzed cross-coupling reactions of aryl and vinyl halides with Grignard reagents, Tamura and Kochi described an iron-catalyzed vinylation reaction of Grignard reagents with vinyl halides (Scheme 5.1) [6]. 

After Kumada and Tamao and Corriu independently reported the nickel(II) salts-and complexes-catalyzed cross-coupling reaction of Grignard reagents with aryl and alkenyl halides, the Pd-catalyzed reaction of Grignard reagents was first reported by Murahashi. ... 

Tamao, K., Sumitani, K., Kiso, Y., Zembayashi, M., Fujioka, A., Kodama, S., Nakajima, I., Minato, A., Kumada, M. Nickel-phosphine complex-catalyzed Grignard coupling. I. Cross-coupling of alkyl, aryl, and alkenyl Grignard reagents with aryl and alkenyl halides general scope and limitations. Bull. Chem. Soc. Jpn. 1976, 49, 1958-1969. 

Many alkynyl, alkenyl, aryl, and functionalised alkyl-lithiums behave well in alkylation reactions because they are more stable anions than those derived from the simple unfunctionalised alkyl halides with which they are to react. Examples are 24, 25, and 26 and these will be treated in later chapters with the reactions of Grignard reagents with allyl halides. 

The crosscoupling of aryl Grignard reagents with organic halides is generally referred to as Kharasch reaction. See Kharasch MS, Fields EK (1941) J Am Chem Soc 63 2316... 

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