Carbon-centered nucleophiles Grignard reagents

Other kinds of propargylic-substituted products were prepared by this procedure. When Grignard reagents such as allylic and homoallylic magnesium bromides are used in place of lithium enolates as carbon-centered nucleophiles. 

In the first systematic study on nucleophilic substitutions of chiral halides by Group IV metal anions, Jensen and Davis showed that (S )-2-bromobutane is converted to the (R)-2-triphenylmetal product with predominant inversion at the carbon center (Table 5)37. Replacement of the phenyl substituents by alkyl groups was possible through sequential brominolysis and reaction of the derived stannyl bromides with a Grignard reagent (equation 16). Subsequently, Pereyre and coworkers employed the foregoing Grignard sequence to prepare several trialkyl(s-butyl)stannanes (equation 17)38. They also developed an alternative synthesis of more hindered trialkyl derivatives (equation 18). 

Reaction with even harder nucleophiles such as organolithiums and Grignard reagents is substantially limited by virtue of the fact that these carbon nucleophiles add by direct attack at the metal center, as opposed to the softer carbon nucleophiles which add by attack on the allyl ligand. Direct metal addition can lead to the opening of alternative reaction pathways, e.g. 3-H elimination, in competition with reductive elimination which accomplishes nucleophile allylation (equation 40). 

The Grignard reagent also functions as a good nucleophile in nucleophilic addition reactions of the carbonyl group. The carbonyl group has electrophilic character at its carbon atom (due to resonance), and a good nudeophile seeks out this center for addition. 

Grignard reagents, R-MgX or Ar-MgX, are typically prepared by the reaction of an alkyl halide, R-X, or an aryl halide, Ar-X, with magnesium metal in an anhydrous ethereal solvent (Eq. 19.3) the organometallic reagent dissolves as it is formed. You may note that carbon is transformed from an electrophilic center in the starting material R-X or Ar-X into a nucleophilic center in the product R-MgX or Ar-MgX in this process. 

Reaction of Trimethylsilylacetylene/Acetylide with Electrophiles. Deprotonation of TMSA with n-BuLi or Grignard reagents produces nucleophilic acetylides, which can react with various electrophilic carbon centers such as carbonyls, alkyl halides, or epoxides. 

The addition of Grignards and organolithium reagents proceeds by attack at the metal center in ir-allylpalladium complexes. The regiochemical selectivity exhibited by these hard carbon nucleophiles with ir-allyl complexes substituted at the termini with alkyl or aryl groups is comparable to the soft carbon nucleophiles (ligand attack) in most cases, with addition occurring predominantly at the less substituted terminus (equations 248 and 249).1591387... 

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