Page 1198 - Advanced Organic Chemistry Part B - Reactions & Synthesis

1174 span a period of several decades and in some cases new reagents and protocols may
have been developed since a particular synthesis was completed. Owing to limitations
CHAPTER 13 of space, only key steps are discussed although all the steps are shown in the schemes.
Multistep Syntheses Usually, only the reagent is shown, although other reaction components such as acids,
bases, or solvents may also be of critical importance to the success of the reaction.

13.2.1. Juvabione
Juvabione is a terpene-derived ketoester that has been isolated from various
plant sources. There are two stereoisomers, both of which occur naturally with R-
configuration at C(4) of the cyclohexene ring and are referred to as erythro- and
threo-juvabione. The 7 S -enantiomer is sometimes called epijuvabione. Juvabione
exhibits “juvenile hormone” activity in insects; that is, it can modify the process of
metamorphosis. 18

6 1 CO CH 6 1 CO CH
9 7 2 3 7 2 3
CH 3 11 R 4 R 2 CH 3 11 9 S 4 R 2
12 12
CH 3 O CH H CH 3 O CH H
13 14 3 13 14 3
threo -juvabione erythro -juvabione

In considering the retrosynthetic analysis of juvabione, two factors draw special
attention to the bond between C(4) and C(7). First, this bond establishes the stereo-
chemistry of the molecule. The C(4) and C(7) carbons are stereogenic centers and their
relative configuration determines the diastereomeric structure. In a stereocontrolled
synthesis, it is necessary to establish the desired stereochemistry at C(4) and C(7).
The C(4)−C(7) bond also connects the side chain to the cyclohexene ring. As a cyclo-
hexane derivative is a logical candidate for one key intermediate, the C(4)−C(7) bond
is a potential bond disconnection.
Other bonds that merit attention are those connecting C(7) through C(11). These
could be formed by one of the many methods for the synthesis of ketones. Bond discon-
nections at carbonyl centers can involve the O=C-C( ) (acylation, organometallic
addition), the C( )–C( ) bond (enolate alkylation, aldol addition), or C( )–C( ) bond
(conjugate addition to enone).
β α′ γ ′

γ α β′
O CH 3

The only other functional group is the conjugated unsaturated ester. This functionality is
remote from the stereocenters and the ketone functionality, and does not play a key role
in most of the reported syntheses. Most of the syntheses use cyclic starting materials.
Those in Schemes 13.4 and 13.5 lead back to a para-substituted aromatic ether. The
syntheses in Schemes 13.7 and 13.8 begin with an accessible terpene intermediate. The
syntheses in Schemes 13.10 and 13.11 start with cyclohexenone. Scheme 13.3 presents
a retrosynthetic analysis leading to the key intermediates used for the syntheses in
18
For a review, see Z. Wimmer and M. Romanuk, Coll. Czech. Chem. Commun., 54, 2302 (1989).