Aryl Grignard reagents alkylation

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. 

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 ... 

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

The corresponding bromides and iodides show concentration-dependent behavior and in very dilute solutions they exist as monomers. In tetrahydrofuran, there is less tendency to aggregate, and several alkyl and aryl Grignard reagents have been found to be monomeric in this solvent. 

A catalyzed asymmetric alkylation of glutaric anhydrides has yet to appear. However, Fu has reported that stoichiometric amounts of sparteine efficiently mediate the addition of aryl Grignard reagents to 4-substituted glutaric anhydrides, providing the 5-ketoacids in good yields and excellent enantioselectivities ... 

Imidazolidinone 0-tosyloxime 6k was also reported to react with alkyl and aryl Grignard reagents in good yields (Scheme 65). The resulting iV-organylimines can be hydrolyzed with CsOH to afford primary amines and/or reduced with LiAlH4 to A-methyl secondary amines. 

Following these results with the salen complex, Bedford reported on the synthesis of a series of Fe(iii)-salen-type complexes and the use of one of them, 75 (Figure 14), for the coupling of aryl Grignard reagents with primary and secondary alkyl halides, in Et20 at 45 Fiirstner subsequently reported on the use of the tetrakis(ethylene)fer-... 

The behavior of BnMgBr (5d) is similar to that observed for compounds with higher alkyl groups, i.e. only the coupling product was detected and the earlier report on the additional formation of benzyl alcohol was not confirmed. On the other hand, reactions of Ar" radicals formed in the anodic oxidation of aryl Grignard reagents are different from those established for Aik, as is evident from the percent distribution of parent radicals in major products given in Table 7. 

D. Iron-catalyzed Alkylation of Aryl Grignard Reagents. 615... 

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). 

TABLE 8. Cross-coupling between aryl Grignard reagents and alkyl bromides... 

Organomercury compounds undergo a similar reaction.388 Alkyl and aryl Grignard reagents can be converted to carboxylic esters with Fe(CO)s instead of CO.389... 

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