Page 673 - Advanced Organic Chemistry Part B - Reactions & Synthesis

648 is higher for the t-butoxy ether than for ethers with smaller groups. There are several
means of preparing ketones using organolithium reagents. Apart from addition to
CHAPTER 7 carboxylate salts (Entries 11 to 13), acylation with acyl chlorides (Entry 14), anhydrides
Organometallic (Entry 15), or N-methoxy-N-methylcarboxyamides (Entry 16) can be used. Carboxylic
Compounds of Group I
and II Metals acids can be made by carbonation with CO (Entries 17 and 18). Aldehydes can be
2
prepared by reactions with DMF (Entry 19). Entry 20 is the alkylation of a stabilized
allylic lithium reagent.

CH
CH 3 N(i -Pr) 2 3
– CH 3 N(i -Pr) 2
O
CH 2 O
Li +

In addition to applications as nucleophiles, the lithium reagents have enormous
importance in synthesis as bases and as lithiating reagents. The commercially available
methyl, n-butyl, s-butyl, and t-butyl reagents are used frequently in this context.

7.2.2.3. Stereoselectivity of Addition to Ketones. The stereochemistry of the addition
of both organomagnesium and organolithium compounds to cyclohexanones is
similar. 116 With unhindered ketones, the stereoselectivity is not high but there is
generally a preference for attack from the equatorial direction to give the axial alcohol.
This preference for the equatorial approach increases with the size of the alkyl group.
With alkyllithium reagents, added salts improve the stereoselectivity. For example,
one equivalent of LiClO , enhances the proportion of the axial alcohol in the addition
4
of methyllithium to 4-t-butylcyclohexanone. 117
OH CH 3
O CH Li
t-Bu 3 t-Bu CH 3 + t-Bu OH

no LiClO 4 65% 35%
1 equiv LiClO 4 92% 8%

Bicyclic ketones react with organometallic reagents to give the products of addition
from the less hindered face of the carbonyl group.
The stereochemistry of addition of organometallic reagents to chiral carbonyl
compounds parallels the behavior of the hydride reducing agents, as discussed in
Section 5.3.2. Organometallic compounds were included in the early studies that
established the preference for addition according to Cram’s rule. 118

M M R′
O R′MgX
L L OMgX
S R S R
S, M, L = relative size of substituents

116
E. C. Ashby and J. T. Laemmle, Chem. Rev., 75, 521 (1975).
117 E. C. Ashby and S. A. Noding, J. Org. Chem., 44, 4371 (1979).
118
D. J. Cram and F. A. A. Elhafez, J. Am. Chem. Soc., 74, 5828 (1952).