1 - Formation of carbon–carbon single bonds

Summary

The formation of carbon–carbon single bonds is of fundamental importance in organic synthesis. As a result, there is an ever-growing number of methods available for carbon–carbon bond formation. Many of the most useful procedures involve the addition of organometallic species or enolates to electrophiles, as in the Grignard reaction, the aldol reaction, the Michael reaction, alkylation reactions and coupling reactions. Significant advances in both main-group and transition-metal-mediated carbon–carbon bond-forming reactions have been made over the past decade. Such reactions, which have been finding useful application, are discussed in this chapter. The formation of carbon–carbon single bonds by pericyclic or radical reactions are discussed in chapters 3 and 4.

Main-group chemistry

Alkylation of enolates and enamines

It is well known that carbonyl groups increase the acidity of the proton(s) adjacent (α-) to the carbonyl group. Table 1.1 shows the pK_a values for some unsaturated compounds and for some common solvents and reagents.

The acidity of the C–H bonds in these compounds is caused by a combination of the inductive electron-withdrawing effect of the unsaturated groups and the resonance stabilization of the anion formed by removal of a proton (1.1). Not all groups are equally effective in ‘activating’ a neighbouring CH; nitro is the most powerful of the common groups, with the series following the approximate order NO₂>COR>SO₂R>CO₂R>CN>C₆H₅. Two activating groups reinforce each other; for example, diethyl malonate has a lower pK_a (≈13) than ethyl acetate (pK_a ≈ 24).