Biomedical Engineering Reference
In-Depth Information
8.8. THEMEYER-SCHUSTERANDRUPE REARRANGEMENTS
The Meyer-Schuster rearrangement [10] consists of the acid-catalyzed isomerization
of secondary and tertiary propargyl alcohols into the corresponding
a
,
b
-unsaturated
carbonyl derivative through a formal 1,3-hydroxyl shift and tautomerization [156]
(Scheme 8.32). Thus, Meyer-Schuster rearrangement is basically a two-stage ole-
fination method that complements other known reactions, such as Wittig olefination,
Horner-Wadsworth-Emmons olefination, Horner-Wittig olefination, and Peterson
olefination. Propargylic alcohols are easily accessible, especially by addition of
acetylide reactive species to carbonyl compounds, and extremely versatile precursors
for different applications in organic synthesis. The Meyer-Schuster rearrangement is,
however, limited to propargylic alcohols which do not posses
b
-hydrogens, while the
Rupe rearrangement [157] is preferred when a
b
-hydrogen is present. Hence, the Rupe
rearrangement takes place when a tertiary propargylic alcohol is treated under acidic
conditions and corresponds to a formal 1,2-shift of the hydroxyl group to afford an
a
,
b
-unsaturated ketone (Scheme 8.32).
This divergence between the Meyer-Schuster rearrangement and the Rupe
rearrangement can be explained by considering the accepted mechanism [158] of
these two transformations. Indeed, while a
b
-elimination of water provides the enyne
intermediate in the Rupe rearrangement, the
g
-addition of water leads to the allenol
intermediate in the Meyer-Schuster rearrangement (Scheme 8.33).
The initial harsh experimental conditions (acid media, high temperatures) [10]
have recently evolved toward milder conditions that have simultaneously addressed
the Meyer-Schuster rearrangement/Rupe rearrangement competition. For instance,
treatment of propargylic alcohols substituted by electron-donating groups on the
R
1
O
OH
Protic acid or Lewis acid
(a)
R
1
R
3
R
3
R
2
Meyer-Schuster rearrangement
R
2
R
1
O
R
1
OH
1. Protic acid or Lewis acid
(b)
R
4
H
R
2
2. H
2
O
Rupe rearrangement
R
2
R
3
R
3
R
4
SCHEME 8.32
Meyer-Schuster rearrangement (a) and Rupe rearrangement (b).
H
H
R
1
R
5
OH
R
1
R
5
O
R
1
R
5
H
R
4
R
4
R
4
R
2
R
3
R
2
R
2
R
3
R
3
Rupe rearrangement
Meyer-Schuster rearrangement
(R
5
= H)
(R
5
H)
R
5
R
1
R
5
R
3
R
1
O
R
2
R
1
R
2
R
4
O
R
4
R
2
R
1
R
3
R
3
OH
R
4
R
4
R
3
R
2
SCHEME 8.33
Mechanism of the Meyer-Schuster and Rupe rearrangements.
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