2.3.3 Oxygenation Reactions
Enzymes which catalyze the direct incorporation of molecular oxygen into an organic
molecule are called ‘oxygenases’ [1173–1176]. Enzymatic oxygenation reactions are
particularly intriguing since direct oxyfunctionalization of nonactivated organic
compounds remains a largely unresolved challenge to synthetic chemistry. On the
one hand, there are numerous (catalytic) oxidation processes developed by industry to
convert simple raw materials, such as alkanes, alkenes and aromatics at the expense
of O 2 into more valuable intermediate products, such as alcohols, aldehydes, ketones
and carboxylic acids.
34 However, the catalysts employed are highly sophisticated and
thus show a very narrow substrate range, which limits their applicability to a single
(or few) substrate(s) and they cannot be used on lab-scale for a wider range of organic
compounds, except for the Wacker-oxidation of alkenes. Unsurmountable problems
persist where regio- or enantiospecificity is desired.
The appealing use of O 2 as zero-priced oxidant comes with some drawbacks: Its
triplet ground state makes it kinetically unreactive with organic molecules, which
are in the singlet state, and it tends to form radical species, which are difficult to
control and tend to cause side reactions. Furthermore, it is a four-electron oxidant,
which makes it difficult to terminate an oxidation process at an intermediate stage,
leading to ‘over-oxidation’. However, nature has managed to tame O 2 to a remarkable extent and several highly selective oxygenation reactions may be achieved by
means of biocatalysts.
Oxygen-transfer from molecular oxygen into organic acceptor molecules may
proceed through three different mechanisms (Scheme 2.144).
• Monooxygenases incorporate one oxygen atom from molecular oxygen into the
substrate, the other is reduced at the expense of a donor (usually NADH or
NADPH) to form water [1177–1179]. Overall this is a four-electron transfer,
comprising two electrons each from the substrate and the cofactor.
• Dioxygenases simultaneously incorporate both oxygen atoms of O 2 into the
substrate by forming a peroxy-species in a two-electron transfer.
35
• Oxidases catalyze electron-transfer onto molecular oxygen, which proceeds via
a two- or (more rarely) a four-electron transfer yielding either hydrogen peroxide
or water, respectively, as byproduct. Incorporation of O into the substrate does
34 The most important processes with respect to scale are: p-xylene ! terephthalic acid, ethylene ! ethylene oxide, ethylene ! acetaldehyde, ethylene/HOAc ! vinyl acetate, methanol ! formaldehyde, acetaldehyde ! acetic acid.
35 Although they are redox enzymes belonging to EC class 1, occasionally they have been
misleadingly called ’oxygen transferases’.
2.3 Oxidation Reactions
173
Enzymes which catalyze the direct incorporation of molecular oxygen into an organic
molecule are called ‘oxygenases’ [1173–1176]. Enzymatic oxygenation reactions are
particularly intriguing since direct oxyfunctionalization of nonactivated organic
compounds remains a largely unresolved challenge to synthetic chemistry. On the
one hand, there are numerous (catalytic) oxidation processes developed by industry to
convert simple raw materials, such as alkanes, alkenes and aromatics at the expense
of O 2 into more valuable intermediate products, such as alcohols, aldehydes, ketones
and carboxylic acids.
34 However, the catalysts employed are highly sophisticated and
thus show a very narrow substrate range, which limits their applicability to a single
(or few) substrate(s) and they cannot be used on lab-scale for a wider range of organic
compounds, except for the Wacker-oxidation of alkenes. Unsurmountable problems
persist where regio- or enantiospecificity is desired.
The appealing use of O 2 as zero-priced oxidant comes with some drawbacks: Its
triplet ground state makes it kinetically unreactive with organic molecules, which
are in the singlet state, and it tends to form radical species, which are difficult to
control and tend to cause side reactions. Furthermore, it is a four-electron oxidant,
which makes it difficult to terminate an oxidation process at an intermediate stage,
leading to ‘over-oxidation’. However, nature has managed to tame O 2 to a remarkable extent and several highly selective oxygenation reactions may be achieved by
means of biocatalysts.
Oxygen-transfer from molecular oxygen into organic acceptor molecules may
proceed through three different mechanisms (Scheme 2.144).
• Monooxygenases incorporate one oxygen atom from molecular oxygen into the
substrate, the other is reduced at the expense of a donor (usually NADH or
NADPH) to form water [1177–1179]. Overall this is a four-electron transfer,
comprising two electrons each from the substrate and the cofactor.
• Dioxygenases simultaneously incorporate both oxygen atoms of O 2 into the
substrate by forming a peroxy-species in a two-electron transfer.
35
• Oxidases catalyze electron-transfer onto molecular oxygen, which proceeds via
a two- or (more rarely) a four-electron transfer yielding either hydrogen peroxide
or water, respectively, as byproduct. Incorporation of O into the substrate does
34 The most important processes with respect to scale are: p-xylene ! terephthalic acid, ethylene ! ethylene oxide, ethylene ! acetaldehyde, ethylene/HOAc ! vinyl acetate, methanol ! formaldehyde, acetaldehyde ! acetic acid.
35 Although they are redox enzymes belonging to EC class 1, occasionally they have been
misleadingly called ’oxygen transferases’.
2.3 Oxidation Reactions
173