Synthesis of 3-Substituted Catechols
FULL PAPERS
+
atom% D) from Aldrich. cis-Dihydrodiols B [R=H, F, Cl,
120.90, 142.37, 144.98; EI-MS: m/z=178 (M , 100%), 159
(17), 158 (82).
[12,27]
Br, I, Me, CN, CF , CF CH(OH)]
and cis-tetrahydro-
3
3
diols D [R=H, F, Cl, Br, I, CF , CF CH(OH)], which had
3
3
[13,27,35-38]
been fully characterised,
studies. Catechols C [R=Cl, Br, I, Me, CF CH(OH)], isolat-
ed during this study, showed identical physical and spectral
characteristics to those reported.
were available from earlier
Biotransformation Using P. putida UV4 to Yield cis-
Dihydrodiols B
3
[
2,3,7,40]
Biotransformation procedures employed for arene sub-
strates A (including 1,5-D - and D -toluene) with whole
2
8
cells of P. putida UV4, a proprietary constitutive mutant
strain derived from the wild type strain P. putida NCIB
(
(
Rꢀ )=- c Mi s -e( )1 S,2R)-3-Methyl-3-cyclohexene-1,2-diol D
1
1767, were identical to those reported earlier for the pro-
[3,12,35,36]
White solid; mp 83–858C; [a] : ꢀ155 (c 1.00, CHCl ); MS:
duction of cis-dihydrodiols B.
D
3
+
1
m/z=128.0863 [M ], calcd. for C H O : 128.0837; H NMR
7
12
2
(
1
300 MHz): d=1.70 (2H, m, 6-H ,6-H ), 1.82 (3H, d, J =
Biotransformation Using E. coli nar B to Yield
Catechols C
A
B
Me,4
.8 Hz, Me), 2.04–2.12 (2H, m, 5-H , 5-H ), 2.72 (2H, br s,
A B
OH), 3.75 (1H, m, 1-H), 3.92 (1H, d, J =3.3 Hz, 2-H), 5.56
2
,1
13
E. coli nar B was grown at 378C in Luria broth (LB)
(1H, m, 4-H); C NMR (125 MHz): d=21.17, 24.24, 25.85,
ꢀ
3
+
medium. Antibiotic ampicillin (0.1 mgcm ) was added to
the culture medium to maintain plasmid-harbouring cells.
iso-Propyl-b-d-thiogalactopyranoside (IPTG), an enzyme-in-
7
7
0.02, 70.58, 125.95, 133.99; MS (EI): m/z=128 (M , 1%),
0 (100).
ꢀ
3
ducer, was added (0.05 mgcm ) before inoculation of the
liquid LB-media for the cell-growth. Cells were harvested,
in late exponential growth phase, by centrifugation, washed
and re-suspended (shake flasks; OD600 =5–10) in potassium
phosphate buffer (50 mM, pH 7.2) prior to the biotransfor-
(
(
+)-cis-(1S,2R)-3-t-butyl-3,5-cycloxadiene-1,2-diol B
R=t-Bu)
White solid; mp 52–548C; [a] : +9 (c 1.10, MeOH); MS:
D
+
m/z=168.1137 [M ], calcd. for C H O : 168.1150;
1
0
16
2
ꢀ
3
1
mation at 308C. Substrates (0.5–2.0 mgcm ) were added
separately and the reaction was terminated after 18 h. The
catechols were extracted from the aqueous medium using
EtOAc and were purified by flash column chromatography
H NMR (300 MHz): d=1.14 (9H, s, t-Bu), 2.10 (1H, br s,
OH), 3.18 (1H, br s, OH), 4.02 (1H, d, J2,1 =4.8 Hz, 2-H),
4
5
4
3
.40 (1H, m, 1-H), 5.63 (1H, m, 6-H), 5.80 (1H, dd, J4,5
=
.4 Hz, J4,2 =0.6 Hz, 4-H), 5.92 (1H, ddd, J =5.4 Hz, J5,6
.7 Hz, J5,1 =2.7 Hz, 5-H); C NMR (125 MHz): d=29.77,
=
5,4
1
3
(
silica gel, 25% EtOAc in hexane).
5.42, 60.82, 72.70, 117.94, 124.24, 130.35, 149.92; EI-MS:
+
m/z=168 (M , 30%), 150 (64), 94 (100).
Typical Heterogeneous Catalysed Reaction of cis-
Dihydrodiols B and Recycling of Catalyst
(
(
ꢀR )=- c ti -s B- ( u1 )S ,2R)-3-t-butyl-3-cyclohexene-1,2-diol D
The heterogeneously catalysed reactions were carried out,
using a magnetically stirred, sealed, 50-cm round-bottom
3
flask fitted with a gas reservoir. The reservoir was filled with
gas from a gas manifold consisting of a number of independ-
ent calibrated mass flow controllers, feeding the gases into a
mixing chamber. The gases were purged through the system
to ensure the correct concentrations and good mixing before
being filling the reservoir.
White solid. mp 77–798C; [a] : ꢀ65 (c 1.00, MeOH); MS:
d
+
1
m/z=170.1325 [M ], calcd. for C H O : 170.1307; H NMR
1
0
18
2
(
300 MHz): d=1.12 (9H, s, t-Bu), 1.73 (2H, m, 6-H , 6-H ),
A B
2
.20 (4H, m, 5-H , 5-H , 2OH), 3.59 (1H, m, 1-H), 4.21
A B
(
1H, d, J2,1 =3.0 Hz, 2-H), 5.69 (1H, dd, J =2.8 Hz, J4,5B =
4,5A
13
4
3
1
.6 Hz, 4-H); C NMR (125 Hz): d=24.29, 29.17, 30.34,
+
Unless stated otherwise, the catalyst 10%wt Pd/C (0.005–
5.49, 66.83, 71.56, 123.61, 145.82; EI-MS: m/z=170 (M ,
0
.04=Pd/substrate) was placed in the reactor with methanol
%), 111 (100).
3
(
ca. 18 cm ) and heated to 308C. After purging the solution
and headspace of the reactor for 20 min with gas from the
reservoir, a solution of cis-dihydrodiol in methanol (2 cm )
(
(
Rꢀ )=- c Ci s N- ( )1 S,2R)-3-cyano-3-cyclohexene-1,2-diol D
3
was injected into the vessel so that the final substrate con-
centration was 80 mM. The reaction mixture was stirred at
1000 rpm. For benzene cis-dihydrodiol precursors B (R=Br,
I), the catalyst was pre-activated by stirring (2 h) in an at-
mosphere of hydrogen.
Viscous oil; [a] : ꢀ64 c 1.12, MeOH); MS: m/z=139.0626
d
+
1
[M ], calcd. for C H NO : 139.0633; H NMR (500 MHz):
7 9 2
d=1.59–1.79 (2H, m, 6-H , 6-H ), 2.04 (1H, m, 5-H ), 2.20
A
B
A
(
1H, m, 5-H ), 3.91 (1H, m, 1-H), 4.14 (1H, d, J2,1 =5.2 Hz,
B
In the recycling of catalyst experiments, after completion
of each cycle, the catalyst was filtered from the reaction
mixture, washed several times with small volumes of metha-
nol, dried and weighed. In each case, the repeat reaction
was conducted using a slightly reduced weight of substrate,
to take into account the small loss of catalyst occurring
during sampling and recovery procedures.
2
-H), 6.43 (1H, dd, J4,5A =2.6 Hz, J4,5B =4.2 Hz, 4-H);
13
C NMR (125 MHz): d=25.12, 26.92, 68.78, 73.91, 119.03,
+
132.14, 141.11; EI-MS: m/z=139 (M , 2%), 121 (4), 95-
A
C
H
T
R
E
U
N
G
(100).
3
-Trifluoromethyl-1,2-benzenediol C (R=CF3)
+
White solid; mp 39–428C; MS: m/z=178.0240 [M ], calcd.
for C H O F : 178.0241; H NMR (300 MHz): d=5.86 (2H,
1
7
5
2
3
br s, OH), 6.88 (1H, m, 5-H), 7.07 (2H, m, 4-H, 6-H);
13
C NMR (125 MHz): d=117.94, 118.47, 118.54, 119.07,
Adv. Synth. Catal. 2007, 349, 727 – 739
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
737