Mutant strains of Pseudomonas putida harboring toluene dioxygenase or naphthalene dioxygenase lacking the dihydrodiol dehydrogenase show broad substrate
tolerance for ring substituents R
1 and R
2 by maintaining excellent stereospecificity
(Scheme 2.169). Consequently, they have been widely employed for the asymmetric dihydroxylation of substituted aromatics [1422] and an impressive number of
>300 arenes have been converted into the corresponding chiral cis-glycols with
excellent optical purities, even on ton-scale with productivities of 20 g L
À1 h
À1 and
product titers exceeding 80 g L
À1 [1423–1427]. The stereoselectivity of the oxygen
addition can be predicted with some accuracy using a substrate model (Scheme
2.169) [1428–1430].
The substrates need not necessarily be mono- or poly-substituted aromatic
compounds such as those shown in Scheme 2.169, but may also be extended
monocyclic- [1431], polycyclic- [1432], and heterocyclic derivatives [1433, 1434].
In order to gain access to products showing opposite configuration, a substrate
modification approach using p-substituted benzene derivatives was developed. Thus,
when p-iodo derivatives were used instead of the unsubstituted counterparts, the
orientation of the oxygen addition was reversed, caused by the switch in relative size
of substituents (I > F, I > CH 3 ). Subsequent removal of the iodine (which served as
directing group) by catalytic hydrogenation led to mirror-image products [1435].
OH
OH
R 1
OH
OH
I
R 1
H
OH
OH
R 1
R
2
R 1
OH
OH
*
*
H 2 , Pd/C
Pseudomonas sp.
mutant
*
*
Pseudomonas sp.
mutant
R
2 < R
1
R
1 < I
F, Me
H, Me, Et, n-Pr, i-Pr, n-Bu, t-Bu,
Et-O,n-Pr-O, Halogen, CF 3 , Ph,
Ph-CH 2 ,Ph-CO,CH 2 =CH,
CH 2 =CH-CH 2 , HC C
L
L = large
S = small
O 2
O 2
H
R
1
R 2
I
S
Relative size
R
1 > R 2
R
2 > R
1
Scheme 2.169 Enantiocomplementary synthesis of cis-glycols
NAD(P)H
NAD(P)
+
Fdx
FdR
Fe
3+
/2Fe2S
e
FeS
Diox
FAD
Sub
Sub
+ O 2 + H
+
OH
OH
FdR = Ferredoxin Reductase
FAD = Flavin adenine dinucleotide
Fdx = Ferredoxin
FeS = iron-sulfur cluster
Diox = Dioxygenase
2Fe2S = Rieske-center
e
O
O
Asp205
N
HN
His208
N
N H
His104
O
Fe
3+
O
His213
O
O
Asp362
Rieske-center
el-Shuttle
Catalytic site
Fe
S Fe
S
Cys81—S
Cys101—S
His83
R
Fig. 2.18 Electron-transport chain and catalytic center of Rieske-type naphthalene dioxygenase
2.3 Oxidation Reactions
197
tolerance for ring substituents R
1 and R
2 by maintaining excellent stereospecificity
(Scheme 2.169). Consequently, they have been widely employed for the asymmetric dihydroxylation of substituted aromatics [1422] and an impressive number of
>300 arenes have been converted into the corresponding chiral cis-glycols with
excellent optical purities, even on ton-scale with productivities of 20 g L
À1 h
À1 and
product titers exceeding 80 g L
À1 [1423–1427]. The stereoselectivity of the oxygen
addition can be predicted with some accuracy using a substrate model (Scheme
2.169) [1428–1430].
The substrates need not necessarily be mono- or poly-substituted aromatic
compounds such as those shown in Scheme 2.169, but may also be extended
monocyclic- [1431], polycyclic- [1432], and heterocyclic derivatives [1433, 1434].
In order to gain access to products showing opposite configuration, a substrate
modification approach using p-substituted benzene derivatives was developed. Thus,
when p-iodo derivatives were used instead of the unsubstituted counterparts, the
orientation of the oxygen addition was reversed, caused by the switch in relative size
of substituents (I > F, I > CH 3 ). Subsequent removal of the iodine (which served as
directing group) by catalytic hydrogenation led to mirror-image products [1435].
OH
OH
R 1
OH
OH
I
R 1
H
OH
OH
R 1
R
2
R 1
OH
OH
*
*
H 2 , Pd/C
Pseudomonas sp.
mutant
*
*
Pseudomonas sp.
mutant
R
2 < R
1
R
1 < I
F, Me
H, Me, Et, n-Pr, i-Pr, n-Bu, t-Bu,
Et-O,n-Pr-O, Halogen, CF 3 , Ph,
Ph-CH 2 ,Ph-CO,CH 2 =CH,
CH 2 =CH-CH 2 , HC C
L
L = large
S = small
O 2
O 2
H
R
1
R 2
I
S
Relative size
R
1 > R 2
R
2 > R
1
Scheme 2.169 Enantiocomplementary synthesis of cis-glycols
NAD(P)H
NAD(P)
+
Fdx
FdR
Fe
3+
/2Fe2S
e
FeS
Diox
FAD
Sub
Sub
+ O 2 + H
+
OH
OH
FdR = Ferredoxin Reductase
FAD = Flavin adenine dinucleotide
Fdx = Ferredoxin
FeS = iron-sulfur cluster
Diox = Dioxygenase
2Fe2S = Rieske-center
e
O
O
Asp205
N
HN
His208
N
N H
His104
O
Fe
3+
O
His213
O
O
Asp362
Rieske-center
el-Shuttle
Catalytic site
Fe
S Fe
S
Cys81—S
Cys101—S
His83
R
Fig. 2.18 Electron-transport chain and catalytic center of Rieske-type naphthalene dioxygenase
2.3 Oxidation Reactions
197