M. Kamenova-Nacheva et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
9
0
0
reaction progress was monitored by TLC (hexane/ethyl
acetate = 2:1). After stirring for 1 h the mixture was quenched with
CDCl
3
, 300 K): d = 7.01 (d, 1H, 2 -H, J = 1.3 Hz), 6.95 (d, 1H, 3 -H,
0
J = 1.3 Hz), 6.33 (br s, 1H, OH), 4.76 (quint, 1H, 4 -H), 4.48–4.47
⁄
⁄
water (20 ml), extracted with Et
phase was dried over anhydrous Na
rated in vacuo and the crude product was chromatographed
2
O (3 ꢁ 30 ml) and the organic
(m, 1H, 16-H), 4.28–4.26 (m, 1H, 14-H), 4.22–4.20 (m, 1H, 15-
H), 4.18–4.16 (m, 1H, 13-H), 4.16 (s, 5H, Cp), 3.79 (d, 1H, 10-H
J = 14.9 Hz), 3.11 (d, 1H, 10-H , J = 14.9 Hz), 3.06 (d, 1H, 4-H,
J = 4.3 Hz), 2.85 (s, 6H, SO NMe ), 2.42 (ddd, 1H, 6-Hexo, J = 13.8,
2
SO . The solvent was evapo-
4
a
,
b
(
(
160 g silica gel, hexane/ethyl acetate = 5:1) to give pure 30
0.450 g, 52%) as a deep orange solid and 37 (0.187 g, 22%) as an
2
2
12.2, 3.6 Hz), 2.09–1.95 (m, 1H, 5-Hexo), 1.57–1.42 (m, 1H, 5-Hendo),
0
orange oil in form of diastereomeric mixture of two isomers (major
7a and minor 37b) in ratio 10:1.
1.39 (d, 3H, 5 -H
1.20 (d, 3H, 5 -H
NMR (62.90 MHz, CDCl
a
, J = 6.8 Hz), 1.32 (s, 3H, 8-H), 1.22 (s, 3H, 9-H),
, J = 6.8 Hz), 1.18–1.05 (m, 1H, 6-Hendo).
, 300 K): d = 149.31 (1C, 1 -C), 144.32 (1C,
3-C), 126.74 (1C, 2 -C), 124.60 (1C, 11-C), 117.02 (1C, 3 -C), 83.30
(1C, 12-C), 81.15 (1C, 2-C), 70.23 (1C, 13-C), 69.02 (1C, 14-C),
69.00 (5C, Cp), 68.28 (1C, 15-C), 67.58 (1C, 16-C), 55.38 (1C, 1-
C), 51.14 (1C, 4-C), 49.44 (1C, 7-C), 47.84 (1C, 4 -C), 42.79 (1C,
), 25.62 (1C, 6-C), 24.32 (1C, 5-C),
24.27 (2C, 5 -C), 22.34 (1C, 8-C), 21.68 (1C, 9-C). MS (EI) m/z (rel.
int.): 565 (M , 5), 455 (100), 281 (30), 227 (30). Anal. calcd for C29
0
13
3
b
C
2
0
0
Data of 30: Mp 162–164 °C. [
a]
D
= 0 (the measurement failed
3
0
0
because no light penetrates through the deep colored solution even
1
⁄
at c 0.02, CHCl
3
). H NMR (600 MHz, CDCl
3
, 293 K): d = 8.16 (br s,
0
0
⁄
1
7
H, OH), 7.59 (t, 1H, 4 -H, J = 7.5 Hz), 7.10 (d, 1H, 5 -H, J = 7.7 Hz),
.06 (d, 1H, 3 -H, J = 7.5 Hz), 5.50 (s, 1H, 11-H), 4.18 (br s 1H, 16-
H), 4.14 (br s 1H, 14-H), 4.12 (br s 1H, 13-H), 4.11 (br s, 1H, 15-
H), 3.99 (s, 5H, Cp), 3.49 (d, 1H, 1 -H
0
0
⁄
⁄
10-C), 37.67 (2C, SO
2
NMe
2
0
0
b
, J = 14.7 Hz), 3.31 (d, 1H,
, J = 14.7 Hz), 2.78 (s, 6H,
0
+Å
1
0-H
a
, J = 14.6 Hz), 2.93 (d, 1H, 1 -H
a
-
SO NMe
2
2
), 2.77 (d, 1H, 10-H
b
, J = 14.6 Hz), 2.73 (d, 1H, 4-H,
H
39FeN
3 3
O S (565.55): C, 61.59; H, 6.95; Fe, 9.87; N, 7.43; S, 5.67.
0
J = 5.4 Hz), 2.59 (s, 3H, 7 -H), 2.39–2.34 (m, 1H, 6-Hexo), 2.09–2.00
Found: C, 61.70; H, 6.88; Fe, 9.94; N, 7.57; S, 5.59%.
(
8
m, 2H, 5-Hexo, 6-Hendo), 1.44–1.39 (m, 1H, 5-Hendo), 1.05 (s, 3H,
13
-H), 1.04 (s, 3H, 9-H). C NMR (150.92 MHz, CDCl
3
, 293 K):
4.12.
1-((1S,2R,4S,E)-2-(Benzo[b]thiophen-2-yl)-3-ferrocenyl-
0
0
d = 159.18 (1C, 2 -C), 156.52 (1C, 6 -C), 151.33 (1C, 3-C), 137.55
methylidene-2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-yl)-
N,N-dimethylmethanesulfonamide 32
0
0
0
(
1C, 4 -C), 122.50 (1C, 3 -C), 121.24 (1C, 5 -C), 117.82 (1C, 11-C),
8
6
1
1
3.05 (1C, 12-C), 81.67 (1C, 2-C), 69.05 (1C, 13-C), 68.82 (5C, Cp),
8.22 (1C, 15-C), 68.14 (1C, 14-C), 67.91 (1C, 16-C), 53.62 (1C,
⁄
⁄
To a solution of benzothiophene (0.27 g, 1.98 mmol) in 20 ml of
THF was added dropwise n-BuLi (1.36 ml, 2.18 mmol of 1.6 M solu-
tion in hexane) at ꢀ50 °C. The mixture was stirred for 30 min at
ꢀ10 °C, then cooled to ꢀ60 °C and 9 (0.30 g, 0.66 mmol) was added
at this temperature. After slowly warming to room temperature
and stirring for 40 min, the mixture was quenched with water
-C), 50.33 (1C, 4-C), 50.25 (1C, 7-C), 43.59 (1C, 10-C), 43.43 (1C,
0
-C), 37.64 (2C, SO
2 2
NMe ), 26.09 (1C, 6-C), 25.17 (1C, 5-C), 24.27
0
(
1C, 7 -C), 22.00 (1C, 8-C), 20.95 (1C, 9-C). MS (EI) m/z (rel. int.):
+Å
5
62 (M , 35), 455 (100), 347 (33), 281 (26), 107 (40). Anal. calcd
38FeN S (562.54): C, 64.05; H, 6.81; Fe, 9.93; N, 4.98;
for C30
H
2 3
O
S, 5.70. Found: C, 64.20; H, 6.76; Fe, 9.77; N, 5.03; S, 5.80%.
(5 ml), extracted with Et
was dried over anhydrous Na
vacuo and the crude product was chromatographed (180 g silica
2
O (3 ꢁ 20 ml) and the organic phase
Data for 37a: (the major diastereoisomer 37a was isolated in
2
SO . The solvent was evaporated in
4
4
3
3
3 mg quantity as orange-yellow solid by crystallization of mixture
1
7a/37b from heptane/CH
00 K): d = 7.51 (t, 1H, 4 -H, J = 7.6 Hz), 7.06 (d, 1H, 5 -H,
2
Cl
2
= 90:10). H NMR (250 MHz, CDCl
3
,
gel, toluene/Et
Mp 113–115 °C. [
2
O = 20:1), to give 32 (0.263 g, 65%) as a yellow solid.
0
0
20
1
a
]
D
= ꢀ256.3 (c 1.00, CHCl
3
). H NMR (600 MHz,
0
⁄
0
⁄
J = 7.6 Hz), 7.00 (d, 1H, 3 -H, J = 7.8 Hz), 4.13–4.08 (m, 4H, Fc),
CDCl
3
, 293 K): d = 7.72 (dd, 1H, 7 -H, J = 6.1, 2.8 Hz), 7.33 (dd, 1H,
0
0
0
0
0
4
3
5
.10 (s, 5H, Cp), 3.68–3.61 (m, 1H, 1 -H
a
), 3.33–3.26 (m, 1H, 4-H),
4 -H, J = 6.1, 2.8 Hz), 7.35–7.32 (m, 2H, 5 -H, 6 -H), 7.23 (s, 1H, 2 -
0
⁄
.19 (d, 1H, 10-H
a
, J = 14.7 Hz), 3.07 (dd, 1H, 1 -H
b
, J = 13.7,
, 11), 2.55
H), 6.27 (s, 1H, 11-H), 4.44–4.43 (m, 1H, 16-H), 4.33–4.32 (m,
1H, 14-H), 4.31–4.30 (m, 1H, 13-H), 4.27–4.26 (m, 1H, 15-H),
⁄
.5 Hz), 2.80 (s, 6H, SO
2
NMe
2
), 2.63–2,58 (m, 2H, 10-H
b
0
⁄
(
s, 3H, 7 -H), 2.43–2.31 (m, 1H, 5-Hexo), 1.67–1.64 (m, 1H, 3-H),
4.21 (s, 5H, Cp), 3.51 (d, 1H, 10-H
a
, J = 14.9 Hz), 3.34 (d, 1H, 10-
NMe ),
⁄
1
1
3
1
.59–1.53 (m, 2H, 6-Hendo, 6-Hexo), 1.42–1.31 (m, 1H, 5-Hendo),
b
H , J = 14.9 Hz), 2.94 (d, 1H, 4-H, J = 4.6), 2.92 (s, 6H, SO
2
2
⁄
⁄
13
.06 (s, 3H, 8-H), 0.77 (s, 3H, 9-H). C NMR (62.90 MHz, CDCl
3
,
2.75 (s, 1H, OH), 2.35 (ddd, 1H, 6-Hexo, J = 13.2, 12.3, 4.6 Hz),
2.13–2.07 (m, 1H, 5-Hexo), 1.59–1.55 (m, 1H, 5-Hendo), 1.51–1.47
0
0
00 K): d = 214.65 (1C, 2-C), 160.05 (1C, 2 -C), 157.75 (1C, 6 -C),
36.38 (1C, 4 -C), 120.64 (1C, 3 -C), 120.36 (1C, 5 -C), 92.69 (1C,
2-C), 69.64 (1C, Fc), 68.50 (5C, Cp), 67.22 (1C, Fc), 67.04 (1C, Fc),
0
0
0
13
(m, 1H, 6-Hendo), 1.27 (s, 3H, 8-H), 1.26 (s, 3H, 9-H). C NMR
0
1
(150.92 MHz, CDCl
3
, 293 K): d = 150.15 (1C, 1 -C), 144.32 (1C, 3-
0
0
0
0
6
4
NMe
6.27 (1C, Fc), 59.18 (1C, 1-C), 55.33 (1C, 11-C), 47.62 (1C, 3-C),
C), 139.77 (1C, 8 -C), 138.90 (1C, 3 -C), 124.40 (2C, 5 -C, 6 -C),
0
0
0
6.65 (1C, 7-C), 44.74 (1C, 1 -C), 43.92 (1C, 10-C), 37.39 (2C, SO
2
-
123.56 (1C, 4 -C), 123.29 (1C, 2 -C), 122.73 (1C, 11-C), 122.16 (1C,
⁄
0
⁄
0
⁄
⁄
2
), 37.35 (1C, 4-C), 25.01 (1C, 5-C), 24.50 (1C, 7 -C), 20.82
7 -C), 85.35 (1C, 12-C), 81.15 (1C, 2-C), 69.45 (1C, 15-C), 68.90
(1C, 14-C), 68.88 (1C, 13-C), 68.82 (5C, Cp), 67.97 (1C, 16-C),
5.02 (1C, 1-C), 51.47 (1C, 4-C), 49.98 (1C, 7-C), 43.49 (1C, 10-C),
37.76 (2C, SO NMe ) 27.59 (1C, 6-C), 22.44 (1C, 5-C), 22.43 (1C,
8-C), 21.89 (1C, 9-C). MS (EI) m/z (rel. int.): 589 (M , 100), 573
(27), 480 (77), 463 (19), 415 (51), 343 (74). Anal. calcd for C31
FeNO (589.59): C, 63.15; H, 5.98; Fe, 9.47; N, 2.38; S, 10.88.
Found: C, 63.31; H 5.88; Fe, 9.54; N, 2.26; S, 10.69%.
⁄
⁄
(
1C, 6-C), 20.06 (1C, 8-C), 19.36 (1C, 9-C).
5
4
.11. 1-((1S,2R,4S,E)-3-Ferrocenylmethylidene-2-hydroxy-2-(1-
2
2
+Å
isopropyl-1H-imidazol-2-yl)-7,7-dimethylbicyclo[2.2.1]heptan-
1
-yl)-N,N-dimethylmethanesulfonamide 31
35
H -
3 2
S
To a solution of 1-isopropyl-1H-imidazole (0.22 g, 1.98 mmol)
in 4 ml of hexane and 4 ml of THF was added dropwise n-BuLi
1.20 ml, 2.97 mmol of 2.5 M solution in hexane) at ꢀ90 °C. The
mixture was stirring for 1 h at this temperature, after which 9
0.30 g, 0.66 mmol) was added. The reaction progress was moni-
tored by TLC (Et O/NH = 6:0.01). After stirring for additional
(
4.13. 1-((1S,2R,4S,E)-3-Ferrocenylmethylidene-2-(dibenzo[b,d]
thiophen-4-yl)-2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-
yl)-N,N-dimethylmethanesulfonamide 33
(
2
3
1
.5 h at ꢀ40 °C, the mixture was quenched with water (5 ml),
To a solution of dibenzothiophene (0.37 g, 1.98 mmol) in 20 ml
of THF was added dropwise n-BuLi (1.36 ml, 2.18 mmol of 1.6 M
solution in hexane) at ꢀ20 °C. The mixture was stirred for 3 h at
0 °C and 2 h at room temperature. Next, 9 (0.30 g, 0.66 mmol)
was added at 0 °C. After stirring for 1 h at room temperature the
extracted with Et
2
O (3 ꢁ 20 ml) and the organic phase was dried
SO . The solvent was evaporated in vacuo
and the crude product was chromatographed (90 g silica gel,
Et O/NH = 6:0.01), to give 31 (0.178 g, 48%) as a yellow solid.
Mp 86–87 °C. [
over anhydrous Na
2
4
2
3
2
0
1
a]
D
= ꢀ339.0 (c 0.64, CHCl
3
). H NMR (250 MHz,
2
mixture was quenched with water (5 ml), extracted with Et O