Microbial Defluorination/Oxygenation of Fluorocycloalkyl N-Phenylcarbamates
Transformation of cis-4-Fluorocyclooctyl N-Phenylcarbamate (15): 11 H, ϪCH
FULL PAPER
, ϪOH), 4.19 (m, 1 H, CHOH), 4.90 (m, 1.5 H, CHF,
2
Together with the starting material (229 mg, 19%), five products, CHOCO), 4.9 (m, 0.5 H, CHF), 6.59 (br. s, 1 H, ϪNH), 7.06 (t,
3
3
2
0 to 24, were isolated from three batches (300 mg of 15 each) of
JH,H ϭ 7.2 Hz, 1 H, p-CH), 7.30 (t, JH,H ϭ 7.9 Hz, 2 H, m-CH),
3
13
transformation product by repeated column chromatography and
HPLC.
7.36 (d, JH,H ϭ 7.4 Hz, 2 H, o-CH) ppm. C NMR: δ ϭ 26.3 (d,
3
2
J
C,F ϭ 7.4 Hz, C-2), 29.9 (s, C-8), 28.4 (d, JC,F ϭ 22.8 Hz, C-3),
0.5 (s, C-7), 39.3 (d, JC,F ϭ 22.9 Hz, C-5), 66.5 (d, JC,F ϭ 7.6 Hz,
2
3
3
(؊)-4-Oxocyclooctyl N-Phenylcarbamate (20): Yield: 162 mg (17%).
1
C-6), 74.4 (s, C-1), 89.6(d, JC,F ϭ 165.3 Hz, C-4), 118.7 (s, o-C),
23.5 (s, p-C), 129.1 (s, m-C), 137.9 (s, ipso-C), 152.9 (s, CϭO)
20
20
M.p. 90Ϫ92 °C (petroleum ether). [α]589 ϭ Ϫ12.2, [α]578ϭ Ϫ13.0,
1
20
20
). 1H NMR
[
(
α]546 ϭ Ϫ15.0, [α]536 ϭ Ϫ26.1 (c ϭ 0.2, CHCl
CD OD): δ ϭ 1.07Ϫ1.18 (m, 1 H, ϪCH ), 1.47Ϫ1.78 (m, 5 H,
ϪCH
3
19
ppm. F NMR: δ ϭ Ϫ167.8 (m) ppm. MS (GC/MS): m/z (%) ϭ
2
3
2
ϩ
81 (2) [M ], 145 (15), 137 (28), 120 (20), 119 (19), 107 (21), 93
2
), 2.08Ϫ2.50 (m, 6 H, ϪCH
2
), 4.76 (sept, 1 H, CHOCO),
(
100), 79 (61), 65 (24), 55 (41). IR (KBr): ν˜ ϭ 3400 (br. s, ν ϪOH,
.90 (t, 3JH,H ϭ 7.4 Hz, 1 H, p-CH), 7.15 (t, JH,H ϭ 7.6 Hz, 2 H,
3
6
ν ϪNH), 2935 (s, ν ϪCH), 2877 (w, ν ϪCH), 1702 (s, ν CϭO, δ
ϪNH), 1604 (m), 1540 (m), 1447 (m), 1324 (m), 1237 (s), 1103 (w).
High-resolution MS: C15
3
13
m-CH), 7.30 (d, JH,H ϭ 7.6 Hz, 2 H, o-CH) ppm. C NMR: δ ϭ
2
1
2.6 (s), 28.0 (s), 28.4 (s), 30.6 (s), 39.0 (s), 40.6 (s), 74.3 (s, C-1),
18.6 (s, o-C), 120.9 (s, p-C), 129.1 (s, m-C), 137.8 (s, ipso-C), 152.8
H20FNO
3
(281.3). calcd. 299.1771 (for
ϩ
C H19FNO ϩ NH ); found 299.1735.
14 3 4
(s, CϭO), 216.4 (s, C-4) ppm. MS (GC/MS): m/z (%) ϭ 261 (24)
ϩ
[
M ], 142 (18), 137 (22), 120 (12), 119 (85), 107 (16), 93 (58), 91 (؊)-c-4-Fluoro-c-6-hydroxycyclooct-r-1-yl N-Phenylcarbamate (24):
2
0
20
20
(
53), 83 (21), 77 (18), 55 (100). FT-IR (KBr): ν˜ ϭ 3321 (br. s, ν
Yield: 42 mg (4%). [α]589 ϭ Ϫ2.6, [α]578 ϭ Ϫ3.1, [α]546 ϭ Ϫ4.0,
2
0
1
ϪNH), 2939 (s, ν ϪCH), 2863 (s, ν ϪCH), 1727 (br. s, ν CϭO, δ
ϪNH), 1699 (br. s, ν CϭO), 1600 (m), 1551 (s), 1501 (w), 1444 (m), OH), 1.69Ϫ2.27 (m, 10 H, ϪCH
315 (m), 1222 (s), 1051 (m). High resolution MS: C15 NF 0.5 H, CHF), 4.83 (m, 1.5 H, CHF, CHOCO), 6.50 (b. s, 1 H, NH),
); found
[α]536 ϭ Ϫ5.7 (c ϭ 0.7, CHCl
3
). H NMR: δ ϭ 1.52 (br. s, 1 H,
), 3.92 (m, 1 H, CHOH), 4.66 (m,
2
1
19 3
H O
ϩ
4
3
3
(263.3). calcd. 279.1709 (for
C
15
H
19
O
3
NF ϩNH
7.06 (t, JH,H ϭ 7.2 Hz, 1 H, p-CH), 7.3 (t, JH,H ϭ 7.9 Hz, 2 H,
3
13
2
79.1707.
m-CH), 7.36 (d, JH,H ϭ 8.4 Hz, 2 H, o-CH) ppm. C NMR: δ ϭ
2
C-3), 30.7 (s, C-7), 39.7 (d, JC,F ϭ 20.4 Hz, C-5), 68.0 (d, JC,F
1
3
2
6.4 (d, JC,F ϭ 7.6 Hz, C-2), 26.8 (s, C-8), 28.7 (d, JC,F ϭ 22.8 Hz,
cis-4-Fluorooctyl N-(4-Hydroxyphenyl)carbamate (21): Yield: 37 mg
2
3
ϭ
1
(
3.5%). H NMR: δ ϭ 1.41Ϫ2.08 (m, 12 H, ϪCH
J
2
), 4.62 (d sept,
1
2.7 Hz, C-6), 74.5 (s, C-1), 90.6 (d, JC,F ϭ 165.3 Hz, C-4), 118.7
2
H,F ϭ 45.8 Hz, 1 H, CHF), 4.84 (m, 1 H, CHOCO), 4.96 (s, 1 H,
(
s, o-C), 123.5 (s, p-C), 129.1 (s, m-C), 137.8 (s, ipso-C), 152.8 (s,
3
OH), 6.39 (br. s, 1 H, NH), 6.76 (d t, JH,H ϭ 9.1 Hz, 2 H, m-CH),
19
CϭO) ppm. F NMR: δ ϭ Ϫ160.2 (m) ppm. GC/MS: m/z (%) ϭ
2
3
13
7
.2
J
H,H ϭ 8.6 Hz, 2 H, o-CH) ppm. C NMR: δ ϭ 21.3 (d,
ϩ
81 (38) [M ], 137 (78), 120 (12), 119 (28), 107 (14), 93 (100), 91
3
3
J
C,F ϭ 7.6 Hz, C-2), 22.5 (s, C-7), 26.6 (d, JC,F ϭ 7.6 Hz, C-6),
(
8), 81 (24), 55 (51). IR (KBr): ν˜ ϭ 3401 (br. s, ν ϪOH, ν ϪNH),
8.1 (s, 2
2
2
2
C,F
JC,F ϭ 22.9 Hz, C-3), 30.2 (s, C-8), 30.9 (d, J ϭ
2
1
960 (s, ν ϪCH), 2872 (w, ν ϪCH), 1705 (m, ν CϭO), 1601 (m),
543 (w), 1444 (w), 1229 (m). High-resolution MS: C15 20FNO
2
2.9 Hz, C-5), 75.1 (s, C-1), 93.4 (d, JC,F ϭ 165.3 Hz, C-4), 115.8
H
3
(s, o-C), 121.2 (s, m-C), 130.9 (s, ipso-C), 152.1 (s, CϭO), 153.6 (s,
ϩ
(
3 4
281.3). calcd. 281.14271 (for C15H20FNO ϩ NH ); found
19
p-C) ppm. F NMR: δ ϭ Ϫ162.3 (m) ppm. MS (GC/MS): m/z
2
81.14346.
ϩ
ϩ
(%) ϭ 281 (18) [M ], 261 (5) [M Ϫ HF], 153 (85), 135 (18), 109
(
100), 81 (30), 67 (69), 55 (24). FT-IR (KBr): ν˜ ϭ 3392 (br. s, ν Preparation of Mosher’s Esters: Mosher esters of the alcohols (ϩ)-
ϪNH, ν ϪOH), 3317 (br. s, ν ϪNH, ν ϪOH), 2941 (s, ν ϪCH),
22, (Ϫ)-23, and (Ϫ)-24 were synthesized in analogy to a pro-
cedure[ originally discovered by Steglich and Höfle (For details
27]
2
1
871 (w, ν ϪCH), 1701 (s, ν CϭO, δ ϪNH), 1545 (s), 1522 (s),
20 3
441 (m), 1232 (s), 1053 (m). High-resolution MS: C15H O NF see Supporting Information; see also footnote on the first page of
ϩ
(281.3): calcd. 299.1771 (for C15
H
20
O
3
NF ϩ NH
4
); found
this article).
299.1790.
X-ray Crystallographic Study
(
؉)-c-4-Fluoro-c-5-hydroxycyclooct-r-1-yl N-Phenylcarbamate (22):
21
cis-4-Fluorocyclohexyl
N-Phenylcarbamate
(9):
Formula
Yield: 31 mg (3%). M.p. 120 °C (petroleum ether). [α]589 ϭ ϩ1.2
1
C
13
H16FNO
2
, M ϭ 237.27, colorless crystal 0.30 ϫ 0.15 ϫ
3 2
(c ϭ 0.1, CHCl ). H NMR: δ ϭ 1.53Ϫ2.39 (m, 11 H, ϪCH ,
˚
3
2
0.10 mm, a ϭ 5.231(2), b ϭ 37.826(9), c ϭ 6.504(2) A, β ϭ
ϪOH), 4.00 (dd, JC,F ϭ 22.4 Hz, 1 H, CHOH), 4.77 (ddt, JH,F
4
ϪNH), 7.06 (t, JH,H ϭ 7.2 Hz, 1 H, p-CH), 7.30 (t, JH,H ϭ 7.9 Hz,
2
δ ϭ 18.2 (s, C-7), 24.4 (s, JC,F ϭ 22.9 Hz, C-3), 27.5 (s, JC,F
7
C-8), 71.6 (s, JC,F ϭ 20.3 Hz, C-5), 73.6 (s, C-1), 95.3 (s, JC,F
1
ϭ
˚
3
Ϫ3
1
11.71(2)°, V ϭ 1195.6(7) A , ρcalcd. ϭ 1.318 g cm , µ ϭ 8.22
5.9 Hz, 1 H, CHF), 4.91 (m, 1 H, CHOCO), 6.59 (br. s, 1 H,
Ϫ1
3
3
cm , empirical absorption correction via ψ scan data (0.791 Յ T
3
13
Յ 0.922), Z ϭ 4, monoclinic, space group P2
1
/n (No. 14), λ ϭ
H, m-CH), 7.36 (d, JH,H ϭ 7.4 Hz, 2 H, o-CH) ppm. C NMR:
˚
2
3
1.54178 A, T ϭ 223 K, ω/2θ scans, 2690 reflections collected (Ϫh,
ϭ
˚
Ϫ1
3
ϩk, Ϯl), [(sinθ)/λ] ϭ 0.62 A , 2433 independent (Rint ϭ 0.036)
and 1843 observed reflections [I Ն 2 σ(I)], 158 refined parameters,
.6 Hz, C-2 or C-6), 29.9 (d, JC,F ϭ 7.6 Hz, C-2 or C-6), 31.8 (s,
2
1
ϭ
2
R ϭ 0.054, wR ϭ 0.150, max. residual electron density 0.44
70.4 Hz, C-4), 118.6 (s, o-C), 123.4 (s, p-C), 129.1 (s, m-C), 137.8
˚
Ϫ3
19
(Ϫ0.28) e·A , hydrogen at N8 from difference Fourier calculation,
others calculated and all refined as riding atoms. cis-4-Fluorocyclo-
(s, ipso-C), 152.8 (s, CϭO) ppm. F NMR: δ ϭ Ϫ171.9 (m) ppm.
ϩ
ϩ
MS (GC/MS): m/z (%) ϭ 281 (38) [M ], 261 (8) [M Ϫ HF], 145
6), 137 (79), 120 (28), 119 (98), 107 (18), 93 (100), 91 (42), 77 (18),
5 (64). FT-IR (KBr): ν˜ ϭ 3416 (br. s, ν ϪOH, ν ϪNH), 3317 (br.
octyl N-Phenylcarbamate (15): Formula C15
colorless crystal 0.15 ϫ 0.15 ϫ 0.10 mm, a ϭ 5.204(1), b ϭ
2
H20FNO , M ϭ 265.32,
(
5
˚
˚
3
1
ρ
8.171(3), c ϭ 7.647(2) A, β ϭ 109.53(2)°, V ϭ 681.5(2) A ,
Ϫ3 Ϫ1
s, ν ϪOH, ν ϪNH), 2944 (s, ν ϪCH), 2882 (w, ν ϪCH), 1714 (s,
ν CϭO), 1609 (m), 1329 (m), 1447 (m), 1329 (w), 1236 (m). High-
resolution MS: (281.3). calcd. 299.1771 (for
calcd. ϭ 1.293 g cm , µ ϭ 7.75 cm , empirical absorption correc-
tion via ψ scan data (0.893 Յ T Յ 0.927), Z ϭ 2, monoclinic, space
C
15
H
20FNO
3
˚
ϩ
4
group P2
1
(No. 4), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 1602
C
15
H
20FNO ϩ NH ); found 299.1733.
3
˚
Ϫ1
reflections collected (Ϫh, ϩk, Ϯl), [(sinθ)/λ] ϭ 0.62 A , 1450 inde-
(
؊)-c-4-Fluoro-t-6-hydroxycyclooct-r-1-yl N-Phenylcarbamate (23):
pendent (Rint ϭ 0.057) and 1058 observed reflections [I Ն 2 σ(I)],
20
20
20
2
Yield: 62 mg (6%). [α]589 ϭ Ϫ11.8, [α]578 ϭ Ϫ12.4, [α]546 ϭ Ϫ13.9, 173 refined parameters, R ϭ 0.057, wR ϭ 0.145, Flack parameter
20
1
˚
Ϫ3
[α]536 ϭ Ϫ23.6 (c ϭ 0.21, CHCl
3
). H NMR: δ ϭ 1.55Ϫ2.20 (m, Ϫ0.2(5), max. residual electron density 0.33 (Ϫ0.29) e·A , hydro-
Eur. J. Org. Chem. 2003, 2166Ϫ2175
www.eurjoc.org 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2173