Page 385 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

366 in reaction rate comes from the fact that the difference is greater for the small hard
hydroxide ion than for the larger anionic species present at the transition state. 116 It
CHAPTER 3
is generally true that solvation forces are strongest for the small, hard anions and
Structural Effects on decrease with size and softness.
Stability and Reactivity

3.8.2.4. Oxygen versus Carbon Alkylation in Ambident Enolate Anions. Enolate
anions are ambident nucleophiles. Alkylation of an enolate can occur at either carbon
or oxygen. Since most of the negative charge of an enolate is on the oxygen atom, it
might be supposed that O-alkylation would dominate. A number of factors other than
charge density affect the C/O-alkylation ratio and it is normally possible to establish
reaction conditions that favor alkylation on carbon.

O – O
C-alkylation + R′ – X
RC CH2 RCCH 2 R′
O – OR′
O-alkylation + R′ – X
RC CH2 RC CH2

O-Alkylation is most pronounced when the enolate is least solvated. When the
potassium salt of ethyl acetoacetate is treated with ethyl sulfate in the polar aprotic
solvent HMPA, the major product (83%) results from O-alkylation. In THF, where
ion clustering occurs, all of the product is C-alkylated. In t-butyl alcohol, where
the acetoacetate anion is hydrogen bonded by solvent, again only C-alkylation is
observed. 157

– +
O K OC H O
2 5
CH C CHCO C H + (C H O) SO 2 CH C CHCO C H + CH CCHCO C H
2 5
2 2 5
2
3
3
2 2 5
2 2 5
3
C H
2 5
HMPA 83% 15%
t-Butyl alcohol 0% 94%
THF 0% 94%
Higher C/O ratios are observed with alkyl halides than with alkyl sulfonates and
sulfates. The highest C/O-alkylation ratios are given by alkyl iodides. For ethylation of
potassium ethyl acetoacetate in HMPA the product compositions shown below were
obtained. 158

157 A. L. Kurts, A. Masias, N. K. Genkina, I. P. Beletskaya, and O. A. Reutov, Dokl. Akad. Nauk. SSSR
(Engl. Transl.), 187, 595 (1969).
158
A. L. Kurts, N. K. Genkina, A. Masias, I. P. Beletskaya, and O. A. Reutov, Tetrahedron, 27, 4777
(1971).