Solutionsγ-Alkylation of 1,3-dicarbonyl compounds
Exercise 1
Write the products of acetylacetone (2,4-pentanedione) with: (a) 1 eq. of NaH, then benzyl bromide; (b) 2 eq. of NaNH2 in liquid NH3, benzyl bromide, then H3O+.
(a) The monoanion is alkylated at the central (α) carbon: 3-benzyl-2,4-pentanedione. (b) The dianion is alkylated at the terminal (γ) carbon: 6-phenyl-2,4-hexanedione, PhCH2CH2COCH2COCH3.
Exercise 2
Why does the dianion react at the γ carbon and not at α, the most acidic carbon?
Precisely because the α carbon is the most acidic, its charge is highly stabilized by the two carbonyls and is not very nucleophilic. The second charge, at the γ carbon, is stabilized by only one carbonyl: it is the stronger base (and nucleophile) and reacts first. After alkylation the monoanion remains, which is protonated on workup.