EPIMERIZATION OFTEN HAPPENS

1
EPIMERIZATION OFTEN HAPPENS BEFORE E1cb
ELIMINATION
2
EPIMERIZATION
This term usually applies to the inversion of a
hydrogen atom on a stereocenter next to a
carbonyl group and occurs in a basic solution.
This one stereocenter is inverted in a molecule
that has other stereocenters that are not
inverted . This creates an epimer.
Epimers are a type of diastereomer.
3
EPIMERIZATION
NaOH / H2O
R
R
S

R
R
R
fast
-H
epimers
( also diastereomers )
-H
fast
-
H
Rapid proton exchanges invert the stereocenter
between the carbonyls.
planar anion
Removal of a proton makes an anion which is
planar (resonance system). When the proton is
replaced, it can add back to either side of the
planar ion.
eliminates slowly
see next slide
E1cb
If one of the epimers has a lower energy, it
will predominate in the equilibrium.
4
PLANAR ANION
H
TOP
H
..
O
Rotated for clarity.
O
CH3O
Ph
also a part of the pi system
H
BOTTOM
5
DEUTERIUM EXCHANGE AND EPIMERIZATION
deuterium adds back to either side of planar
resonance structure
fast
fast
E1cb
planar sp2
slow