Chemistry Reference
In-Depth Information
Scheme 7.17 Addition of nucleophiles to
a
,
b
-unsaturated carbonyls can result in 1,4-additions.
Scheme 7.18
a
,
b
-Unsaturated carbonyl systems can be sequentially subjected to 1,4-additions and
1,2-additions.
For example, simple organometallic reagents such as alkyllithium reagents and Grignard
reagents tend to participate in 1,2-additions while organocuprates generally participate
in 1,4-additions. These trends, however, are not absolute, and the reader is referred to
general organic chemistry textbooks for broader and more detailed treatments of these
addition mechanisms.
In a final consideration regarding 1,2- and 1,4-addition reactions,
a
,
b
-unsaturated
carbonyl systems can be sequentially subjected to both mechanisms. As illustrated
in Scheme 7.18, if methyl vinyl ketone is treated first with dimethyllithiocuprate and
then with methylmagnesium bromide, the resulting product is 2-methyl-2-pentanol.
7.3.3 Addition-Elimination Reactions
In our present discussions, 1,2- and 1,4-additions to carbonyl systems were introduced.
However, these reactions were not presented in the context of specific carbonyl-based
functional groups. Expanding upon this concept, the three types of functional groups
generally used in addition reactions to carbonyls are aldehydes, ketones, and esters.
With respect to all of the above-mentioned functional groups, 1,4-additions are generally
applicable. However, of these three groups, only aldehydes and ketones are generally
useful as substrates for 1,2-additions. Figure 7.3 illustrates the products resulting from
both 1,2- and 1,4-additions of nucleophiles to aldehydes, ketones, and esters. As shown,
while the products of 1,4-additions all result in retention of the carbonyl functionality,
1,2-additions result in conversion of the respective carbonyl groups into alcohols.
However, when an ester is involved, the illustrated product is a ketone and retains the
carbonyl of the starting ester.
In examining the mechanism leading to the nucleophile-mediated conversion of an ester
to a ketone, initial addition of a nucleophile to the carbonyl results in formation of a hemi-
acetal intermediate. Subsequent collapse of the hemiacetal intermediate liberates a ketone
and an alkoxide leaving group. This mechanistic sequence, illustrated in Scheme 7.19
