Bromine-magnesium exchange

Aldol reactions of simple amide enolates give poor stereoselection. Stimulated by the interest in /3-lactams, the stereochemistry of aldol reactions of chiral magnesium enolates of /3-lactams has been studied . The best results have been obtained with 6,6-dibromopenams 85 (equation 108). After bromine-magnesium exchange with MeMgBr,... 

In 1931 Pr6vost reported the reaction of cinnamyl bromide (13) to cinnamyhnagnesium bromide (14), which was the first example of a bromine-magnesium exchange reaction (equation 10). ... 

TABLE 7. Bromine-magnesium exchange of aryl bromides with BusMgLi... 

Lithium butyldimethylmagnesate was preferable to tributyhnagnesate in the bromine-magnesium exchange of 3-bromopyridine since the latter afforded a rather complex mixture (Table 10)". 2-Bromopyridine and 2-bromothiophene were also converted to the corresponding magnesium reagents which then reacted with aldehydes. 

TABLE 10. Bromine-magnesium exchange of heteroaryl bromides with BuMe2MgLi... 

Since the carbon-carbon bonds in strained cyclopropane rings have large s-character, cyclopropyl bromides underwent smooth bromine-magnesium exchange by the action of lithium tributylmagnesate (equation 27)". 

Lithium dibutylisopropylmagnesate proved to be quite efficient for the bromine-magnesium exchange of 5-bromo-2-picoline at —10 °C (Table 14) . The resulting picolyl-magnesium reagent reacted with electrophiles including thiuram disulfide (last entry). 

Treatment of dibromomethyl methyldiphenylsilane with lithium tributylmagnesate at —78°C induced very efficient bromine-magnesium exchange to yield the bromomethylsilane upon protonolysis at —78°C (Scheme 13)" ". Warming the reaction mixture in the presence of a copper salt before protonolysis led to smooth migration of one of the butyl groups to afford 1-silylpentyhnetal. 

Lithium tris(iec-butyl)magnesate underwent bromine-magnesium exchange, which was followed by 1,2-migration in the absence of CuCN 2LiCl at room temperature (Scheme 15). However, CuCN 2LiCl was essential for the acylation and allylation. 

Polyfunctional aryl bromides, bearing a chelating function ortho to bromine readily undergo a bromine-magnesium exchange.39,40 40a Even the less effective methoxy group directs the substitution in the case of 2,4-dibromoanisole (Scheme 14).41... 

Baird, M. S., Nizovtsev, A. V., Bolesov, I. G. Bromine-magnesium exchange in gem-dibromocyclopropanes using Grignard reagents. Tetrahedron 2002, 58,1581-1593. 

Bromine-magnesium exchange of alkenyl bromides proceeds only occasionally [136]. The presence of an electron-withdrawing group at the position a to the bromine facilitates the exchange reactions. Functionalized alkenyl bromides, e.g. bromonitriles and the bromosulfones are converted to the corresponding organomagnesium derivatives at low temperatures (Scheme 3.108). 

The bromine-magnesium exchange of aryl bromides proceeds on treatment with "BUjMgl.i at O C. Representative examples are shown in Tab. 3.13. 

In contrast, the bromine-magnesium exchange of alkenyl bromides does not... 

Treatment of (dibromomethyl)methyldiphenylsilane with "T)U,Ms- li at -78°C induces clean bromine-magnesium exchange to provide bromomethylsilane. Addition of CuCN 2LiCl (30 mol%) and warming to 0°C induces migration of the butyl group to afford the a-silyl-substituted magnesium species (Scheme 3.119). 

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