Chemistry Reference
In-Depth Information
tion biotransformation. An interesting approach is the use of defatted almond meal in
microaqueous media. The resulting products were obtained in yields of up to 100% and
with excellent enantioselectivities of up to 99% ee [141].
6.4.3. Benzoin Condensation and Related Reactions
This condensation and related reactions thereof belong to the “classic” chemical trans-
formations, known to proceed with cyanide as an achiral catalyst. The development of
enantioselective versions of this type of reaction and related reactions using organocata-
lysts [142] and biocatalysts [143] has gained a lot of interest in the last decade. Notably,
however, an enantioselective version of the synthesis of (
R
) - acetyl phenylcarbinol ((
R
) -
96
) as a related reaction had already been developed in the 1920s by Neumann and has
been applied since the 1930s by Knoll AG as a key step for the production of ephedrine
(Scheme 6.38) [144]. As a catalyst, a pyruvate decarboxylase from baker's yeast is used
in combination with molasses as a starting material. The key reaction is the condensation
of
in situ
- formed pyruvate (
95
) with added benzaldehyde (
91
) under the formation of
α - hydroxyketone (
R
) -
96
with high enantioselectivity. This intermediate is then chemi-
cally transformed into ephedrine via imine formation and subsequent diastereoselective
metal - catalyzed reductive amination.
O
O
OH
Pyruvate decarboxylase
from baker's yeast
CH
3
CH
3
H
+
HO
O
-CO
2
O
91
95
(
In
situ
formed
enzymatically)
(
R
)-
96
Scheme 6.38.
Several recent breakthroughs in the fi eld of benzoin condensation have been achieved
jointly by the groups of Müller and Pohl [145,146]. A key prerequisite was the develop-
ment of effi cient enzymes available in recombinant form. For example, an impressively
broad substrate spectrum leading to the desired carboligation products with excellent
enantioselectivities has been found for the (recombinant) benzoyl formate decarboxyl-
ase from
P. putida
[145]. A synthetically valuable application is the development of an
asymmetric cross-benzoin condensation via enzymatic cross-coupling reactions of differ-
ent aldehydes [146]. By means of this methodology from Müller et al., highly enantio-
merically enriched mixed benzoins are obtained when using two different types of
substituted benzaldehydes in the presence of thiamine diphosphate-dependent enzymes.
A selected example is shown in Scheme 6.39. The Müller and Pohl group achieved the
preferred synthesis of one of these products when using benzaldehyde lyase or a mutant
of a pyruvate decarboxylase as catalysts in such cross-benzoin condensations. For the
formation of these products, typically one of the two aldehydes is preferred as donor,
whereas the other one acts as the preferred acceptor molecule.
Very recently, Degussa researchers in cooperation with Liese and Pohl demonstrated
that whole-cell catalysts containing benzaldehyde lyase in overexpressed form are highly
