OXIDATIVE COUPLING

1
OXIDATIVE COUPLING
OXIDATIVE COUPLING OF PHENOLS
2
PHENOLIC RINGS COUPLE EVEN WITH MILD
OXIDIZING REAGENTS
FeCl3
Fe2
Pt anode
(- e- )
K2S2O8
3
COUPLING PROCEEDS VIA RADICALS FORMED FROM THE
CONJUGATE BASE
anion
..
-
K3Fe(CN)6

ferricyanide
..
KOH
FeIII(CN)6-3
- e-
FeII(CN)6-4
..
ferrocyanide
.
COUPLING !
..
at any of the indicated positions
radical
(has resonance)
Even mild oxidizing agents (like O2 )can initiate
coupling.
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PUMMERERS KETONE
THOUGHT (INCORRECTLY) FOR MANY YEARS TO BE A
MODEL FOR MORPHINE BIOSYNTHESIS
O2
Pummerers ketone
.
one-electron oxidation
Michael addition
.
.
couple
enolization

H

OH2
H
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PHENOLS ARE VERY SENSITIVE TO OXIDATION
Mild oxidizing agents, including oxygen, cause
oxidative coupling.
Stronger oxidants, cleave (destroy) the phenolic
ring, especially if there are multiple phenolic
groups, or the phenolic groups are ortho.
EXAMPLE
O
O
sidechains or other rings may survive as acids
O
O
R-COOH
etc
n CO2
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OXIDATIVE COUPLING MAKES SIMPLE COMPOUNDS
MORE COMPLEX VERY QUICKLY
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APORPHINES
(TWO TYPES)
standard benzylisoquinoline
2 tyrosine
Note how the benzene ring can rotate around its
attachment to make a different substitution patter
n.
O
.
.
.
.
rotate
coupling, rearomatization via enolization, SAM
coupling, rearomatization via enolization, SAM
()-glaucine
()-corydine
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ORIENTALINONE
From a poppy-relative that grows in China.
standard benzylisoquinoline
2 tyrosine
O
.
.
coupling
(S)-orientalinone
NADPH
-H2O

orientalinol
(S)-isothebaine
H
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CULARINE
.
.
SAM
cularine
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AMARYLLIS ALKALOIDS
THREE TYPES
oxidative coupling other steps
A
fold
B
rotate
C
Compounds can fold, twist rings around, and
adopt other conformations before oxidative
coupling takes place. This makes interesting
bicyclics and some variations in the substitution
pattern.
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ERYTHRINA ALKALOIDS
Erythrina crista-galli
H
.
..
.
H
12
(Chondodendron spp)
Arrow poison of South American Indians (pot
curare) another variety , calabash curare, is
made from plants that have steroidal
sapogenins. There are about 30-40 different
plants in the mixture, not all active.
Potency one-tree, two-tree and three-tree (does
not kill) curares are made, depending on how many
trees a monkey will travel to before falling. It
works by paralyzing muscles, including those
necessary for breathing.
(S)-N-methylcoclaurine
.
SAM
coupling
O
enolizations
.
.
.

O
tubocurarine
(R)-N-methylcoclaurine
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NOT JUST ALKALOIDS
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GRISEOFULVIN
(discussed earlier)
POLYKETIDE
SAM
..
Cl
OXIDATIVE COUPLING
reson.
O
.
.
.
.
SAM
FADH2
griseofulvin
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HYPERICIN
ACETOGENIN
emodin-anthrone
.
.
NADPH
O
x2
oxidative coupling
more oxidative coupling
and oxidation
hypericin
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MORPHINE
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BIOSYNTHESIS OF MORPHINE
(details will be given later)
tyrosine
oxidative coupling
ring formation
thebaine
norlaudanosoline
reticuline
morphine