Arylation with aryl Grignard reagents

Activated alkyl halides such as a-bromocarboxylates were arylated with aryl Grignard reagent [Eq. (105) 229]. The expected side reaction is carbonyl addition of the Grignard reagent, and it was minimized by the use of t-butyl ester. 

Selim KB, Matsumoto Y, Yamada K, Tomioka K (2009) Efficient chiral N-heterocyclic carbene/copper(I)-catalyzed asymmetric allylic arylation with aryl Grignard reagents. Angew Chem Int Ed 48 8733-8735... 

Formation of aryl Grignard reagents (Section 14 4) Aryl halides react with magnesium to form the corresponding arylmagnesium halide Aryl iodides are the most reac tive aryl fluorides the least A similar reaction occurs with lithium to give aryllithium reagents (Section 14 3)... 

Anthocyanidins were first synthesi2ed by reaction of an aryl Grignard reagent with a coumarin (93). 

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

Acylated glycosyl thiocyanates are made by treatment of acylated glycopyranosyl halides with potassium thiocyanate.30 Reaction at —40° with a Grignard reagent affords alkyl or aryl 1-thioglycosides.54... 

Organomercury compounds undergo a similar reaction. Alkyl and aryl Grignard reagents can be converted to carboxylic esters with Fe(CO)5 instead of CO. Amides have been prepared by the treatment of trialkyl or triarylboranes with CO and an imine, in the presence of catalytic amounts of cobalt carbonyl ... 

Cross-Coupling of Arylchloridcs with Aryl Grignard Reagents... 

CROSS-COUPLING OF ARYLCHLORIDES WITH ARYL GRIGNARD REAGENTS (KUMADA REACTION)... 

The conversion of diarylthallium trifluoroacetates to aromatic iodides by treatment with molecular iodine is thus analogous to the well-known conversion of diarylmercury derivatives with iodine to a mixture of an aromatic iodide and an arylmercury iodide (134), but it is much more effective as a synthetic tool because of the spontaneous disproportionation to product of the intermediate arylthallium trifluoroacetate iodide. The present procedure thus provides a practical synthetic method for the ultimate conversion of aryl Grignard reagents to aromatic iodides. 

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

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 order of reactivity of halides with magnesium is RI > RBr > RC1 (very few organomagnesium fluorides have been prepared), i) Aryl Grignard reagents are more easily prepared from aryl bromides and aryl iodides than from aryl chlorides, which react very sluggishly. 

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

Biaryl synthesisThis reagent promotes coupling of aryl Grignard reagents to symmetrical biaryls in 70-95% yield with formation of allene and 3-aryl-2-chloropropene as co-products. The reaction is retarded by galvinoxyl and evidently involves an electron-transfer from the Grignard reagent to the dichloropropene. 

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