Page 41 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Under conditions of thermodynamic control, however, it is the enolate corresponding 13
to deprotonation of the -carbon that is present in the greater amount.
SECTION 1.1
O O – O – Generation and
γ NaNH 2
CH 3 CH 3 Properties of Enolates
C CHCCH 3 NH CH 2 C CH CCH > C CH C CH 2 and Other
3
β α α' 3 γ α α' α α' Stabilized Carbanions
CH CH
γ 3 CH 3 γ 3
major enolate 2
1
(more stable) (less stable)
Ref. 21
These isomeric enolates differ in that 1 is fully conjugated, whereas the system in 2
is cross-conjugated. In isomer 2, the delocalization of the negative charge is restricted
to the oxygen and the -carbon, whereas in the conjugated system of 1 the negative

charge is delocalized on oxygen and both the - and -carbon.
It is also possible to achieve enantioselective enolate formation by using chiral
bases. Enantioselective deprotonation requires discrimination between two enantiotopic
hydrogens, such as in cis-2,6-dimethylcyclohexanone or 4-(t-butyl)cyclohexanone.
Among the bases that have been studied are chiral lithium amides such as A to D. 22
CH CH 3 Li
3
Li
N N )
Ph N Ph N N N C(CH 3 3
Li
Li Ph Ph
A 23 B 24 C 25 D 26

Enantioselective enolate formation can also be achieved by kinetic resolution through
preferential reaction of one of the enantiomers of a racemic chiral ketone such as
2-(t-butyl)cyclohexanone (see Section 2.1.8 of Part A to review the principles of
kinetic resolution).

O O OTMS
3 3
C(CH ) 2 C(CH ) C(CH )
3 3 R* NLi (D)
3 3
+
trimethylsilyl
chloride
45% yield, 90% e.e. 51% yield, 94% e.e.
Ref. 25a
21
G. Buchi and H. Wuest, J. Am. Chem. Soc., 96, 7573 (1974).
22 P. O’Brien, J. Chem. Soc., Perkin Trans. 1, 1439 (1998); H. J. Geis, Methods of Organic Chemistry,
Vol. E21a, Houben-Weyl, G. Thieme Stuttgart, 1996, p. 589.
23
P. J. Cox and N. S. Simpkins, Tetrahedron: Asymmetry, 2, 1 (1991); N. S. Simpkin, Pure Appl. Chem.,
68, 691 (1996); B. J. Bunn and N. S. Simpkins, J. Org. Chem., 58, 533 (1993).
24 C. M. Cain, R. P. C. Cousins, G. Coumbarides, and N. S. Simpkins, Tetrahedron, 46, 523 (1990).
25 (a) D. Sato, H. Kawasaki, T. Shimada, Y. Arata, K. Okamura, T. Date, and K. Koga, J. Am. Chem. Soc.,
114, 761 (1992); (b) T. Yamashita, D. Sato, T. Kiyoto, A. Kumar, and K. Koga, Tetrahedron Lett., 37,
8195 (1996); (c) H. Chatani, M. Nakajima, H. Kawasaki, and K. Koga, Heterocycles, 46, 53 (1997);
(d) R. Shirai, D. Sato, K. Aoki, M. Tanaka, H. Kawasaki, and K. Koga, Tetrahedron, 53, 5963 (1997).
26
M. Asami, Bull. Chem. Soc. Jpn., 63, 721 (1996).