Organolithium reagents, addition organocuprates

The reaction of carbon nucleophiles with ketones or aldehydes proceeds by acyl addition, as described in Chapter 18. The reaction of carbon nucleophiles with acid derivatives proceeds by acyl substitution, as described in Chapter 20. Carbon nucleophiles included cyanide, alkyne anions, Grignard reagents, organolithium reagents, and organocuprates. Alkyne anions are formed by an acid-base reaction with terminal alkynes (RC=C-H RCsCr). In this latter transformation, it is clear that formation of the alkyne anion relies on the fact that a terminal alkyne is a weak carbon acid. Other carbon acids specifically involve the proton on an a-carbon in aldehydes, ketones, or esters. With a siiitable base, these carbonyl compounds generate a new type of carbon nucleophile called an enolate anion. 

Before translating this retrosynthetic analysis into a synthesis in the forward direction, notice that the side chain, which we intend to use as a nucleophile for 1,4-addition, will have to be introduced as an organocuprate reagent, which in turn has to come from a halide via an organolithium species. However, it also contains a carbonyl function, which will need to be protected, so that the organolithium reagent can be prepared successfully (recall Section 17-8) ... 

In Summary Organolithium reagents add 1,2 and organocuprate reagents add 1,4 to a,/3-unsaturated carbonyl systems. The 1,4-addition process initiaUy gives rise to a j8-substituted enolate, which upon exposure to haloalkanes furnishes a,j8-dialkylated aldehydes and ketones. 

Grignard and organolithium reagents react by 1,2-addition and organocuprate reagents react by 1,4-addition. 

Improved organocuprate reagents, obtained from CuCN or CuSCN and organolithium (magnesium) compounds, used in addition, substitution, selective ligand transfer, epoxide opening. 

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