DOMINO REACTIONS IN THE ENANTIOSELECTIVE SYNTHESIS OF BIOACTIVE NATURAL PRODUCTS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 269

TABLE 9.1 Classification of Domino Reactions

I. Transformation II. Transformation III. Transformation

1. Cationic 1. Cationic 1. Cationic

2. Anionic 2. Anionic 2. Anionic

3. Radical 3. Radical 3. Radical

4. Pericyclic 4. Pericyclic 4. Pericyclic

5. Photochemical 5. Photochemical 5. Photochemical

6. Transition metal 6. Transition metal 6. Transition metal

7. Oxidative or reductive 7. Oxidative or reductive 7. Oxidative or reductive

8. Enzymatic 8. Enzymatic 8. Enzymatic

cationic, anionic, radical, pericyclic, photochemical, transition metal-catalyzed,
oxidative or reductive, and enzymatic reactions. It should be noted that, as previously
mentioned, some rules have been applied when these classifications are made.
For example, nucleophilic substitutions are always counted as anionic processes
according to the attacking reagent, independent of whether a carbocation intermediate
is formed. Moreover, nucleophilic additions to carbonyl groups with metal organic
compounds such as MeLi, silyl enol ethers, or boron enolates are again counted as
anionic transformations. In this way, aldol reactions and aldol-type reactions such
as the Mukaiyama aldol reaction and the Michael addition are found in the part
dealing with anionic domino processes. A related problem exists in the classification
of radical and oxidative or reductive transformations if a single electron transfer is
included. Here, a differentiation according to the used reagent is employed. Thus,
reactions of bromides with n Bu 3 SnH follow a typical radical pathway, whereas
reactions of, for example, a hydroxyl group with TEMPO/BAIB are listed under
oxidative processes. Following this classification, we can establish a summary of
possible combination of these reactions (Table 9.1).
In the following sections, we classified the syntheses according to the first step
of each domino sequence.

9.2. CATIONIC DOMINO REACTIONS

A major goal in modern medicinal chemistry is the finding of new compounds with
the potential in the treatment of Alzheimer's disease. It was proposed that acetyl-
cholinesterase inhibitors might have some therapeutic effects. In this respect, the
triterpenoid

-onocerin 4 isolated inter alia from Lycopodium clavatum has found

a

some interest [2,3].
Corey and coworkers described a highly efficient synthesis of ( þ )- a -onocerin

(4) using a four-component coupling of an almost enantiopure farnesyl derivative 2 ,

3

followed by an exchange of the two vinyl triflates to afford with two allylsilane

moieties [4]. The last step was a twofold domino cyclization employing AlMeCl 2 and
TBAF to yield

that contained two decalin moities (Scheme 9.1).
Recently, Zhu and Chen devised a new domino

4

-elimination/cyclization reac-
tion in the preparation of complex pentacyclic isoquinoline alkaloids. The formation

b