Page 54 - Advanced Organic Chemistry Part B - Reactions & Synthesis

26 When an additional methyl substituent is placed at C(3), there is a strong preference
for alkylation anti to the 3-methyl group. This is attributed to the conformation of the
CHAPTER 1
enolate, which places the C(3) methyl in a pseudoaxial orientation because of allylic
Alkylation of Enolates strain (see Part A, Section 2.2.1). The axial C(3) methyl then shields the lower face
and Other Carbon 55
Nucleophiles of the enolate.
O – R'
R' X
CH 3 CH 3 CH CH 3 O – CH 3 CH 3 O
3
disfavored
favored
The enolates of 1- and 2-decalone derivatives provide further insight into
the factors governing stereoselectivity in enolate alkylations. The 1(9)-enolate of
1-decalone shows a preference for alkylation to give the cis ring juncture, and this
is believed to be due primarily a steric effect. The upper face of the enolate presents
three hydrogens in a 1,3-diaxial relationship to the approaching electrophile. The
corresponding hydrogens on the lower face are equatorial. 56

O
H H O –
H R X
R
H

The 2(1)-enolate of trans-2-decalone is preferentially alkylated by an axial approach
of the electrophile.

H R H
O – R' X R O

R'
H H

The stereoselectivity is enhanced if there is an alkyl substituent at C(1). The factors
operating in this case are similar to those described for 4-t-butylcyclohexanone. The
trans-decalone framework is conformationally rigid. Axial attack from the lower face
leads directly to the chair conformation of the product. The 1-alkyl group enhances this
stereoselectivity because a steric interaction with the solvated enolate oxygen distorts
57
the enolate to favor the axial attack. The placement of an axial methyl group at C(10)
in a 2(1)-decalone enolate introduces a 1,3-diaxial interaction with the approaching
electrophile. The preferred alkylation product results from approach on the opposite
side of the enolate.
H R H H R'
O – R' X R' O
R
O
CH CH R
CH 3 3 3
55 R. K. Boeckman, Jr., J. Org. Chem., 38, 4450 (1973).
56 H. O. House and B. M. Trost, J. Org. Chem., 30, 2502 (1965).
57
R. S. Mathews, S. S. Grigenti, and E. A. Folkers, J. Chem. Soc., Chem. Commun., 708 (1970);
P. Lansbury and G. E. DuBois, Tetrahedron Lett., 3305 (1972).