2
72
S. Gil et al.
PAPER
1
1
H NMR (CDCl , 400 MHz): = 1.29–1.40 (m, 2 H, CH ), 1.40–
H NMR (CDCl , 400 MHz): = 1.14 (dd, J = 10.4, 2 Hz, 1 H,
3
2
3
1
.60 (m, 1 H, CH ), 1.90–2.00 (m, 2 H, CH ), 2.31 (dt, J = 11.1, 5.7
CHCH CH), 1.35 (m, 2 H, H CHCHCOH and H CHCHCHCl),
2
2
2 eq eq
Hz, 1 H, H CHCHO), 2.56 (m, 1 H, H CHC=), 3.09 (m, 1 H, H -
1.48 (m, 1 H, H CHCHCHOH), 1.68 (m, 1 H, H CHCHCCl), 1.98
ax ax
ax
eq
ax
CHC=), 4.73 (dd, J = 11.1, 6.0 Hz, 1 H, CHO), 7.34–7.49 (m, 5 H,
(m, 1 H, CHCOH), 2.16 (d, J = 10.4 Hz, 1 H, CHCH CH), 2.41 (dd,
2
C H ).
J = 5.2, 1.6 Hz, 1 H, CHCHCl), 3.66 (s, 1 H, CHCO H), 3.90 (d,
6
5
2
1
3
J = 2.0 Hz, 1 H, CHCl), 7.25 (m, 3 H, C
6
H
5
), 7.60 (m, 2 H, C
H ).
6 5
C NMR (CDCl , 300 MHz): = 21.9, 26.4, 26.9 and 34.7 (4 CH2),
3
1
3
7
1
9.9 (CHO), 123.5 (PhCC=O), 128.3, 128.5 and 128.9 (CHAr),
29.0 (CAr), 164.2 (C=CC–O), 172.7 (C=O).
C NMR (CDCl , 100 MHz): = 22.5 (CH CHCOH), 27.3
3
2
(CH CHCHCl), 34.2 (CHCH CH), 46.7 (CHCOH), 47.4
2
2
+
+
(CHCHCl), 55.9 (CHCO
128.4 and 129.8 (5 CHAr), 134.6 (CAr), 177.7 (CO
2
H), 72.0 (CHCl), 81.4 (COH), 127.9,
EIMS: m/z (%) = 214 (M , 100), 186 (M – CO, 21), 185 (65), 158
(
+
+
2
H).
M – C H , 27), 129 (58), 115 (62), 91 (C H ).
4
8
7
7
3
7
+
35
+
37
EIMS: m/z (%) = 282 ( ClM , 0.5), 280 ( ClM , 1.5), 264 ( ClM
HRMS: m/z calcd for C H O , 214.0994; found, 214.0997.
1
4
14
2
35
+
+
–
(
H O, 16), 262 ( ClM – H O, 18), 136 (PhCH CO H , 100), 118
2 2 2 2
The acidic fraction, yellow oil (458 mg, 76%), is a diastereoisomer-
ic mixture (R*,R*,R*:S*,R*,R* = 74:26) and starting acid (23%).
Column chromatography led to the isolation of (2R*,1’R*,2’R*)-8b
as a white solid; mp 135–137 °C.
+
PhCH CO H – H O, 100).
2 2 2
3
7
HRMS: m/z calcd for C H ClO , 282.0837; found, 282.0849; m/
1
5
17
3
3
5
z calcd for C H ClO , 280.0866; found, 280.0867.
1
5
17
3
Further elution allowed the isolation of (2S*,2’S*,3’R*)-8c as yel-
(
2R*,1’R*,2’R*)-2-(2’-Chloro-1’-hydroxycyclohexy1)-2-phen-
low prisms; mp 130 °C (dec.).
ylacetic Acid [(2R& ast;,1’R*,2’R*)-8b]
IR (film): 3442, 2942, 1708, 14,54, 1391, 1226, 984, 742 cm .
–
1
(2S*,2’S*,3’R*)-2-(3’-Chloro-2’-hydroxybicyclo[2.2.1]hept-2’-
yl)-2-phenylacetic Acid [(2S*,2’S*,3’R*)-8c]
1
H NMR (CDCl , 400 MHz): = 1.10 (m, 1 H, CH ), 1.20 (m, 1 H,
3
2
IR (film): 3527, 3200–2850, 1681, 1455, 1217, 948, 926, 724, 696
CH ), 1.45 (m, 1 H, CH ), 1.65 (m, 2 H, CH ), 1.95 (m, 1 H, CH ),
2
2
2
2
–1
cm .
2
1
2
.05 (m, 1 H, CH ), 2.30 (m, 1 H, CH ), 3.74 (dd, J = 11.6, 4.4 Hz,
2
2
1
H, CHCl), 4.31 (s, 1 H, CHCO H), 7.33 (m, 3 H, C H ), 7.50 (m,
H NMR (CDCl , 400 MHz): = 1.20 (m, 1 H, CHCH CH), 1.27
2
6
5
3
2
H, C H ).
(m, 1 H, CH CHCHCl), 1.60 (m, 1 H, CH CHCHOH), 1.67 (m, 2
6
5
2
2
1
3
H, CH
2
CHCCl and CH
2
CHCOH), 2.12 (m, 1 H, CHCH CH), 2.26
2
C NMR (CDCl , 300 MHz): = 20.1, 25.6, 31.8 and 32.7 (4
3
(m, 1 H, CHCHCl), 2.56 (m, 1 H, CHCOH), 3.60 (m, 2 H, CHCO H
2
CH ), 58.0 (CHCO H), 66.6 (CHCl), 75.4 (COH), 128.1, 128.5 and
1
2
2
and CHCl), 7.05–7.25 (m, 5 H, C H ).
6
5
30.0 (5 CHAr), 133.9 (CAr), 177.5 (C=O).
13C NMR (CDCl
(CH CHCHCl), 35.1 (CHCH
CHCOH), 56.3 (CHCO H), 70.5 (CHCl), 80.9 (COH), 128.0,
, 100MHz):
= 23.1 (CH
CH), 46.7 (CHCHCl), 48.4
2
CHCOH), 27.4
3
7
+
35
+
3
2
EIMS: m/z (%) = 271 ( ClM + 1, 30), 269 ( ClM + 1, 100), 253
(
3
7
+
35
+
+
2
ClM – OH, 7), 251 ( ClM – OH, 26), 215 (M – Cl – H O)
2
(
2
3
7
HRMS: m/z calcd for C H ClO , 270.0837; found,270.0834;
m/z calcd for C H ClO , 268.0866; found, 268.0879.
1
4
17
3
128.6 and 129.8 (5 CHAr), 133.9 (CAr), 175.9 (CO H).
2
3
5
14
17
3
37
+
35
+
EIMS: m/z (%) = 264 ( ClM – H O, 1), 262 ( ClM – H O, 3),
2
2
Further elution allowed the isolation of (2S*,1’R*,2’R*)-8b as a
yellow oil.
+
+
1
36 (PhCH CO H , 100), 118 (PhCH CO H – H O, 57), 91
2 2 2 2 2
+
(
C H ).
7 7
3
7
+
HRMS: m/z calcd for C H ClO (M – H O), 264.0731; found,
2
1
5
15
2
2
(
2S*,1’R*,2’R*)-2-(2’-Chloro-1’-hydroxycyclohexy1)-2-
3
5
+
64.0737; m/z calcd for C H ClO (M – H O), 262.0761; found,
15 15 3 2
phenylacetic Acid [(2S*,1’R*,2’R*)-8b]
IR (film): 3480, 2960, 1710, 1430, 1226, 1036, 990, 710 cm .
–
1
262.0760.
1
H NMR (CDCl , 400 MHz): = 1.50 (m, 1 H, CH ), 1.70 (m, 2 H,
3
2
Reaction of Phenylacetic Acid (4) with 2-Chlorocycloheptanone
(d)
From phenylacetic acid (4; 306 mg, 2.25 mmol) and 2-chlorocyclo-
heptanone (d; 330 mg, 2.25 mmol). Workup gave a neutral fraction
identified as 3-phenyl-4,5,6,7,8,8a-hexahydro-2H-cyclopenta[b]fu-
ran-2-one (13d; 60 mg, 28%) as a white oil.
CH ), 1.90–2.10 (m, 5 H, 5 CH ), 4.23 (s, 1 H, CHCO H), 4.35 (t,
J = 6.2 Hz, 1 H, CHCl), 7.26–7.38 (m, 5 H, C H ).
2
2
2
6
5
1
3
C NMR (CDCl , 300 MHz): = 20.6, 24.6, 31.0 and 32.5 (4
3
CH ), 58.2 (CHCO H), 66.5 (CHCl), 74.4 (COH), 128.0, 128.4 and
1
2
2
30.2 (5 CHAr), 133.3 (CAr), 177.1 (C=O).
3
5
+
EIMS: m/z (%) = 268 ( ClM , 3), 136 (PhCH CO H, 88), 135
2
2
3
-Phenyl-4,5,6,7,8,8a-hexahydro-2H-cyclopenta[b]furan-2-one
3
7
+
35
+
(
(
ClM – PhCHCO H, 2), 133 ( ClM – PhCHCO H, 4), 118
2
2
(
13d)
+
+
PhCH CO H – H O, 58), 91 (C H , 100).
–1
2
2
2
7
7
IR (film): 2930, 2355, 1743, 1449, 1321, 1147, 1023, 754, 697 cm .
3
5
HRMS: m/z calcd for C H ClO , 268.0866; found, 268.0859.
1
1
4
17
3
H NMR (CDCl , 400 MHz): = 1.35 (m, 1 H, CH CH CH C=),
3
2
2
2
1
.59 (m, 3 H, CH CH CHO), 1.93 (m, 3 H, CH CH CH C=), 2.45
2 2 2 2 2
2
-(3’-Chloro-2’-hydroxybicyclo[2.2.1]hept-2’-yl)-2-phenylacet-
(
m, 1 H, CH CHO), 2.85 (m, 2 H, CH C=), 5.02 (m, 1 H, CHO),
2
2
ic Acid (8c)
7
.26–7.52 (m, 5 H, C H ).
6
5
From phenylacetic acid (4; 306 mg, 2.25 mmol) and 3-chloronor-
bornan-2-one (c; 325 mg, 2.25 mmol). Workup gave the product a
colorless solid (460 mg, 76%) as a diastereoisomeric mixture
1
3
C NMR (CDCl , 75 MHz):
= 25.9 (CH CH C=), 26.3
2 2
3
(
(
CH CH CHO), 28.9 (CH C=), 30.0 (CH CH CH C=), 33.9
CH CHO), 83.4 (CHO), 125.7 (C=CPh), 128.5, 128.6 and 128.9 (5
2 2 2 2 2 2
(
2R*,2’S*,3’R*:2S*,2’S*,3’R* = 50:50). Column chromatography
led to the isolation of (2R*,2’S*,3’R*)-8c as a white solid; mp
40 °C (dec.).
2
CHAr), 130.7 (CAr), 167.0 (PhC=C), 173.0 (C=O).
1
+
+
+
EIMS: m/z (%) = 228 (M , 100), 200 (M – CO, 15), 199 (M –
C H , 20), 185 (M – C H O, 15), 172 (M – C H , 45).
+
+
2
5
2
3
4
8
(
2R*,2’S*,3’R*)-2-(3’-Chloro-2’-hydroxybicyclo[2.2.1]hept-2’-
HRMS: m/z calcd for C H O , 228.1150; found, 228.1152.
1
5
16
2
yl)-2-phenylacetic Acid [(2R*,2’S’*,3’R*)-8c]
IR (film): 3507, 2956–2622, 1693, 1453, 1364, 1220, 947, 918, 817,
The acidic fraction, brown oil (312 mg, 56%), was a mixture of ep-
oxyacid and -lactone and starting acid (43%). Column chromatog-
–1
7
23 cm .
Synthesis 2002, No. 2, 265–273 ISSN 0039-7881 © Thieme Stuttgart · New York