peroxycarboxylic acids or hypervalent transition metal complexes based on V and
Mo. Owing to these drawbacks, the number of industrial-scale oxidation processes
using H 2 O 2 as the oxidant is very limited.
40 On the other hand, biocatalytic
activation of H 2 O 2 by peroxidases allow a number of synthetically useful and
often highly enantioselective peroxidation reactions, which offer a valuable alternative to traditional chemical methodology.
Peroxidases [EC 1.11.1.X] are a heterogeneous group of redox enzymes found
ubiquitously in various sources [1451], such as plants [1452], microorganisms [1453]
and animals. They are often named after their sources (e.g., horseradish peroxidase,
lacto- and myeloperoxidase) or akin to their substrates (e.g., cytochrome c-, halo- and
lignin peroxidase). Although the biological role of these enzymes is quite diverse—
ranging from disproportionation of H 2 O 2 , free radical oligomerization and polymerization of electron-rich aromatics to the oxidation and halogenation of organic substrates—they have in common that they accept hydrogen peroxide or an alkyl
hydroperoxide as oxidant. In line with these diverse catalytic activities, the mechanism of action may be quite different and can involve a heme unit, selenium
(glutathione peroxidase) [1454], vanadium (bromoperoxidase) [1455, 1456], manganese (manganese peroxidase) [1457] and flavin at the active site (flavoperoxidase)
[1458]. The largest group of peroxidases studied so far are heme-enzymes with ferric
protoporphyrin IX (protoheme) as the prosthetic group. Their catalytic cycle bears
strong similarities to that of heme-dependent monooxygenases (Sect. 2.3.3, Scheme
2.146), but their pathways are more complex (Scheme 2.171). The mechanism of
heme-dependent peroxidase catalysis has been largely deduced from horseradish
peroxidase [1178, 1459–1461] and its key features are described as follows:
In its native state, the Fe
3+ species is coordinated equatorially by a heme unit and
axially by a histidine residue and is therefore very similar to cytochrome P
450 [1462]. Activation occurs via a two-electron oxidation at the expense of
H 2 O 2 via the peroxide-shunt to form Compound I. The latter contains a Fe
+4
¼O
π-radical moiety and is two oxidation steps above the Fe
+3 ground state; (in the
monooxygenase pathway, the Fe
3+ -ground state is oxidized by O 2 , which requires
two additional electrons from a nicotinamide cofactor to cover the net redox
balance). Compound I represents the central hypervalent oxidizing species, which
can react along two major pathways:
• Peroxidase-path: Abstraction of a single electron from an electron-rich substrate such as a phenol, an enol or halide forms a substrate radical and yields an
Fe
+4
¼O species denoted Compound II. Since the latter is still one oxidation step
above the Fe
+3 -ground state, this process can occur a second time forming
another substrate radical, to finally re-form the enzyme in its native state.
• Peroxygenase-path: Alternatively, Compound I can incorporate an O-atom
onto a substrate via a two-electron transfer in a single step. Although formally
this reaction should be denoted as ‘peroxygenase’-activity, this distinction is not
always made.
40 A well known industrial-scale process is the oxidation of propene to propene oxide using tertBu–OOH.
2.3 Oxidation Reactions
199
Mo. Owing to these drawbacks, the number of industrial-scale oxidation processes
using H 2 O 2 as the oxidant is very limited.
40 On the other hand, biocatalytic
activation of H 2 O 2 by peroxidases allow a number of synthetically useful and
often highly enantioselective peroxidation reactions, which offer a valuable alternative to traditional chemical methodology.
Peroxidases [EC 1.11.1.X] are a heterogeneous group of redox enzymes found
ubiquitously in various sources [1451], such as plants [1452], microorganisms [1453]
and animals. They are often named after their sources (e.g., horseradish peroxidase,
lacto- and myeloperoxidase) or akin to their substrates (e.g., cytochrome c-, halo- and
lignin peroxidase). Although the biological role of these enzymes is quite diverse—
ranging from disproportionation of H 2 O 2 , free radical oligomerization and polymerization of electron-rich aromatics to the oxidation and halogenation of organic substrates—they have in common that they accept hydrogen peroxide or an alkyl
hydroperoxide as oxidant. In line with these diverse catalytic activities, the mechanism of action may be quite different and can involve a heme unit, selenium
(glutathione peroxidase) [1454], vanadium (bromoperoxidase) [1455, 1456], manganese (manganese peroxidase) [1457] and flavin at the active site (flavoperoxidase)
[1458]. The largest group of peroxidases studied so far are heme-enzymes with ferric
protoporphyrin IX (protoheme) as the prosthetic group. Their catalytic cycle bears
strong similarities to that of heme-dependent monooxygenases (Sect. 2.3.3, Scheme
2.146), but their pathways are more complex (Scheme 2.171). The mechanism of
heme-dependent peroxidase catalysis has been largely deduced from horseradish
peroxidase [1178, 1459–1461] and its key features are described as follows:
In its native state, the Fe
3+ species is coordinated equatorially by a heme unit and
axially by a histidine residue and is therefore very similar to cytochrome P
450 [1462]. Activation occurs via a two-electron oxidation at the expense of
H 2 O 2 via the peroxide-shunt to form Compound I. The latter contains a Fe
+4
¼O
π-radical moiety and is two oxidation steps above the Fe
+3 ground state; (in the
monooxygenase pathway, the Fe
3+ -ground state is oxidized by O 2 , which requires
two additional electrons from a nicotinamide cofactor to cover the net redox
balance). Compound I represents the central hypervalent oxidizing species, which
can react along two major pathways:
• Peroxidase-path: Abstraction of a single electron from an electron-rich substrate such as a phenol, an enol or halide forms a substrate radical and yields an
Fe
+4
¼O species denoted Compound II. Since the latter is still one oxidation step
above the Fe
+3 -ground state, this process can occur a second time forming
another substrate radical, to finally re-form the enzyme in its native state.
• Peroxygenase-path: Alternatively, Compound I can incorporate an O-atom
onto a substrate via a two-electron transfer in a single step. Although formally
this reaction should be denoted as ‘peroxygenase’-activity, this distinction is not
always made.
40 A well known industrial-scale process is the oxidation of propene to propene oxide using tertBu–OOH.
2.3 Oxidation Reactions
199