The (S)-hydroxynitrile lyase from Hevea brasiliensis has been made available in
sufficient quantities by cloning and overexpression to allow industrial-scale applications [1751]. Of particular interest is the synthesis of the (S)-cyanohydrin from mphenoxybenzaldehyde (Table 2.6), which is an important intermediate for synthetic
pyrethroids.
Synthetic pyrethroids comprise a class of potent insecticides with structural
similarities to a number of naturally occurring chrysanthemic acid esters found in
the extract of pyrethrum flowers (Chrysanthemum cinerariaefolium) (Scheme
2.208). These natural products constitute highly potent insecticides, but their
OH
N≡C
R 2
R
1
C≡N
HO
R 2
R
1
O
R 2
R 1
buffer pH 3.5
lyase
(S)-hydroxynitrile
lyase
(R)-hydroxynitrile
buffer pH 3.5
HC≡N
S
R
HC≡N
Scheme 2.207 Stereocomplementary asymmetric cyanohydrin formation
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 2.5
Synthesis of (R)-cyanohydrins from aldehydes and ketones
R
1
R
2
e.e. (%)
Ph–
H
94
p-MeO–C 6 H 4 –
H
9 3
2-furyl–
H
98
n-C 3 H 7 –
H
92–96
t-Bu–
H
73
(E)-CH 3 –CH¼CH–
H
69
n-C 3 H 7 –
M e
9 5
n-C 4 H 9 –
M e
9 8
(CH 3 ) 2 CH–(CH 2 ) 2 –
M e
9 8
CH 2 ¼CH(CH 3 )–
Me
94
Cl–(CH 2 ) 3 –
M e
8 4
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 2.6
Synthesis of (S)-cyanohydrins from aldehydes
R
1
R
2
e.e. (%)
Ph–
H
96–98
p-HO–C 6 H 4 –
H
94–99
m-PhO–C 6 H 4 –
H
9 6
3-thienyl–
H
98
n-C 5 H 11 –
H
8 4
n-C 8 H 17 –
H
8 5
CH 2 ¼CH–
H
84
(E)-CH 3 –CH¼CH–
H
92
(E)-n-C 3 H 7 –CH¼CH–
H
97
(Z)-n-C 3 H 7 –CH¼CH–
H
92
n-C 5 H 11 –
C H 3
92
(CH 3 ) 2 CH–CH 2 –
C H 3
91
2.5 Addition and Elimination Reactions
231
sufficient quantities by cloning and overexpression to allow industrial-scale applications [1751]. Of particular interest is the synthesis of the (S)-cyanohydrin from mphenoxybenzaldehyde (Table 2.6), which is an important intermediate for synthetic
pyrethroids.
Synthetic pyrethroids comprise a class of potent insecticides with structural
similarities to a number of naturally occurring chrysanthemic acid esters found in
the extract of pyrethrum flowers (Chrysanthemum cinerariaefolium) (Scheme
2.208). These natural products constitute highly potent insecticides, but their
OH
N≡C
R 2
R
1
C≡N
HO
R 2
R
1
O
R 2
R 1
buffer pH 3.5
lyase
(S)-hydroxynitrile
lyase
(R)-hydroxynitrile
buffer pH 3.5
HC≡N
S
R
HC≡N
Scheme 2.207 Stereocomplementary asymmetric cyanohydrin formation
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 2.5
Synthesis of (R)-cyanohydrins from aldehydes and ketones
R
1
R
2
e.e. (%)
Ph–
H
94
p-MeO–C 6 H 4 –
H
9 3
2-furyl–
H
98
n-C 3 H 7 –
H
92–96
t-Bu–
H
73
(E)-CH 3 –CH¼CH–
H
69
n-C 3 H 7 –
M e
9 5
n-C 4 H 9 –
M e
9 8
(CH 3 ) 2 CH–(CH 2 ) 2 –
M e
9 8
CH 2 ¼CH(CH 3 )–
Me
94
Cl–(CH 2 ) 3 –
M e
8 4
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 2.6
Synthesis of (S)-cyanohydrins from aldehydes
R
1
R
2
e.e. (%)
Ph–
H
96–98
p-HO–C 6 H 4 –
H
94–99
m-PhO–C 6 H 4 –
H
9 6
3-thienyl–
H
98
n-C 5 H 11 –
H
8 4
n-C 8 H 17 –
H
8 5
CH 2 ¼CH–
H
84
(E)-CH 3 –CH¼CH–
H
92
(E)-n-C 3 H 7 –CH¼CH–
H
97
(Z)-n-C 3 H 7 –CH¼CH–
H
92
n-C 5 H 11 –
C H 3
92
(CH 3 ) 2 CH–CH 2 –
C H 3
91
2.5 Addition and Elimination Reactions
231