Grignard reagents, bonding protonation

In general, the reaction can be performed only with organometallics of active metals such as lithium, sodium, and potassium, but Grignard reagents abstract protons from a sufficiently acidic C—H bond, as in R—C=C—H —> R—C=C—MgX. This method is best for the preparation of alkynyl Grignard reagents. ... 

Another feature of the Pd—C bonds is the excellent functional group tolerance. They are inert to many functional groups, except alkenes and alkynes and iodides and bromides attached to sp carbons, and not sensitive to H2O, ROH, and even RCO H. In this sense, they are very different from Grignard reagents, which react with carbonyl groups and are easily protonated. 

Because 2-chloroethanol has a proton bonded to oxygen, it is not an appropriate substrate for conversion to a stable Grignard reagent. 

Reflecting its electronegative character, C q readily undergoes nucleophilic additions with various nucleophiles [7]. Apparently the most fundamental C-C bond forming reaction is the reaction with alkyllithium or Grignard reagents, giving the monoalkylated derivative of l,2-dihydro-C6o after protonation of the initially formed alkyl-Cso carbanion [48]. 

This strategy chapter is rather different. We shall look at one class of starting material—alkynes or acetylenes—and see what special jobs they can do in synthesis. In particular, we shall see how they can solve some problems we have already met. Acetylene itself 3 is readily available and its first important property is that protons on triple bonds are much more acidic than most CH protons. Acetylene forms a genuine anion 4 with sodium in liquid ammonia, a lithium derivative 1 with BuLi and a Grignard reagent 2 by reaction with a simple alkyl Grignard such as EtMgX. 

A ketone has two alkyl groups bonded to its carbonyl carbon atom. Addition of a Grignard reagent, followed by protonation, gives a tertiary alcohol, with three alkyl groups bonded to the carbinol carbon atom. 

Primary and secondary amines are prone to oxidation, and N-H bonds undergo met-allation on exposure to organolithium and Grignard reagents. Moreover, the amino group possesses a lone electron pair, which can be protonated or reacted with electrophiles (R-X). To render the lone pair less reactive, the amine can be converted into an amide via acylation. Protection of the amino group in amino acids plays a crucial role in peptide synthesis. 

The regiochemistry of deprotonation of imines derived from unsymmetrical ketones is of special significance for the synthetic applications of these anions for carbon-carbon bond formation. This selectivity is sensitive to both the amine moiety and the base used. With imines derived from cyclohexyl- or r-butyl-amine, deprotonation with either Grignard reagents or lithium dialkylamide bases will result in high selectivity (>98 2) for removal of the proton on the less substituted a-carbon as in equations (39) and (40). 3i... 

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