First total synthesis of the 7-oxygenated carbazole alkaloids clauszoline-K, 3-formyl-7-hydroxycarbazole, clausine M, clausine N and the anti-HIV active siamenol using a highly efficient palladium-catalyzed approach

Article abstract of DOI:10.1039/b607792g

A short synthesis of the 7-oxygenated carbazole alkaloids clauszoline-K, 3-formyl-7-hydrocarbazole, clausine C, clausine M, clausine N and the anti-HIV active siamenol was investigated. The synthesis was performed using a convergent palladium-catalyzed co

Full text of DOI:10.1039/b607792g

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COMMUNICATION
www.rsc.org/obc | Organic & Biomolecular Chemistry
First total synthesis of the 7-oxygenated carbazole alkaloids clauszoline-K,
3
-formyl-7-hydroxycarbazole, clausine M, clausine N and the anti-HIV active
siamenol using a highly efficient palladium-catalyzed approach†
Micha P. Krahl, Anne J a¨ ger, Tilo Krause and Hans-Joachim Kn o¨ lker*
Received 1st June 2006, Accepted 19th July 2006
First published as an Advance Article on the web 26th July 2006
DOI: 10.1039/b607792g
Using a convergent palladium-catalyzed construction of the
carbazole framework as the key step we have achieved a short
synthesis of the 7-oxygenated carbazole alkaloids clauszoline-
K, 3-formyl-7-hydroxycarbazole, clausine C (clauszoline-L),
clausine M, clausine N and the anti-HIV active siamenol.
Most of the carbazole alkaloids isolated from terrestrial plants
biogenetically derive from 3-methylcarbazole as the common
1,2
precursor. Further metabolic transformation includes oxidation
of the methyl group, oxygenation at different positions, and preny-
lation or geranylation, which could be followed by cyclization.
Therefore, carbazole alkaloids have been classified based on their
1,2
oxygenation pattern. Their broad range of useful biological
1–3
activities induced a strong synthetic interest. The iron-mediated
oxidative coupling of arylamines and cyclohexadienes represents
2,4
the most versatile route to carbazole alkaloids. Recently, this
strategy was applied to the total synthesis of 2,7-dioxygenated
5
carbazoles. Herein, we report a palladium-catalyzed approach to
7
-oxygenated carbazole alkaloids including the first total syntheses
Fig. 1 Naturally occurring 7-oxygenated tricyclic carbazole alkaloids.
bond activation of N,N-diarylamines to furnish the carbazole
of clauszoline-K (1), 3-formyl-7-hydroxycarbazole (2), clausine M
(
(
4), clausine N (5), siamenol (6) and a novel route to clausine C
clauszoline-L) (3) (Fig. 1).
Clauszoline-K (1) and clauszoline-L (3) were isolated by Ito
13
˚
heterocycle was reported first by Akermark et al. For the
synthesis of carbazole-1,4-quinones, we demonstrated first that
this process becomes catalytic in palladium by reoxidation of Pd(0)
et al. in 1997 from the stem bark of the Chinese medicinal
plant Clausena excavata. Wu and his group in Taiwan had
already obtained alkaloid 3 a year before from the same natural
source and named it clausine C. 3-Formyl-7-hydroxycarbazole
6
14
7
to Pd(II) using cupric acetate. Several alternative palladium-
15
catalyzed carbazole constructions have been reported since.
(
2) was isolated by Wu and Furukawa from the root bark of
8
Herein, we describe an optimization of our Pd(II)-catalyzed C–
H bond activation followed by oxidative cyclization and its
application to the generation of the 9H-carbazole skeleton.
The Pd(0)-catalyzed reaction of m-anisidine (7) and p-bromo-
Murraya euchrestifolia. In 1999, Wu’s group reported the isolation
and structural elucidation of clausine M (4) and clausine N
9
(
5) from the root bark of Clausena excavata. One year later,
Boyd and co-workers found that the organic extract of Murraya
siamensis, collected in Thailand, showed anti-HIV activity.
bioassay-guided fractionation of the extract led to the isolation
of siamenol (6), which in the XTT-tetrazolium assay exhibited an
16
10
toluene (8) led quantitatively to the diarylamine 9 (Scheme 1).
A
Cyclization of compound 9 using stoichiometric amounts of
palladium(II) acetate provided 3-methyl-7-methoxycarbazole (10)
17
−
1
in only 36% yield as the best result (Table 1). The structure of 10
HIV inhibitory activity (EC50 = 2.6 lg mL ).
has been confirmed by its spectroscopic data and X-ray analysis
We have developed an efficient approach to the carbazole frame-
work via sequential palladium-catalyzed C–N and C–C bond
(Fig. 2).‡ We found that the oxidative cyclization with catalytic
11
amounts of Pd(II) gave better yields than its stoichiometric version.
Using 10 mol% of Pd(II) and an excess of cupric acetate, carbazole
10 was obtained in 72% yield under optimized conditions (see ex-
perimental section). Using smaller amounts of palladium catalyst
and extended reaction times the turnover number for the catalytic
cycle was even better. We assumed that the reason for the low
yield of 10 in the stoichiometric cyclization is oxidation of the
carbazole under the reaction conditions. In order to support this
hypothesis carbazole 10 (250 mg, 1.18 mmol) was treated with
formation. The Pd(0)-catalyzed Buchwald–Hartwig amination
of an aryl halide with the corresponding arylamine to an N,N-
diarylamine represents the first step. The Pd(II)-mediated C–H
12
Department Chemie, Technische Universit a¨ t Dresden, Bergstrasse 66, 01069
Dresden, Germany. E-mail: hans-joachim.knoelker@tu-dresden.de; Fax: 49
3
51 463 37030
†
Part 81 of Transition Metal Complexes in Organic Synthesis; for Part 80,
see: J. Kn o¨ ll and H.-J. Kn o¨ lker, Tetrahedron Lett., 2006, 47, 6079.
This journal is © The Royal Society of Chemistry 2006
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Table 1 Palladium(II)-catalyzed oxidative cyclization of diarylamine 9 to 7-methoxy-3-methylcarbazole (10)
a
Pd(OAc)
2
Reaction conditions
Yield (%)
TON
1
1
1
5
2
.2 equiv.
HOAc, reflux, argon, 2 h
36
64
72
61
53
—
6.4
7.2
12.2
26.5
0 mol%
0 mol%
mol%
2.5 equiv. Cu(OAc)
2.5 equiv. Cu(OAc)
2.5 equiv. Cu(OAc)
2.5 equiv. Cu(OAc)
2
2
2
2
, HOAc, reflux, air, 23 h
, HOAc, reflux, air, 2 d
, HOAc, reflux, air, 40 h
, HOAc, reflux, air, 6 d
mol%
a
TON = turnover number.
Fig. 3 Molecular structure of 3-formyl-7-hydroxycarbazole (2).
Scheme 1 Palladium-catalyzed synthesis of clauszoline-K (1) and
-formyl-7-hydroxycarbazole (2). Reagents and conditions: (i) 6 mol%
Pd(OAc) , 5 mol% rac-BINAP, Cs CO , toluene, reflux, 16 h, 100%;
ii) 10 mol% Pd(OAc) , 2.5 equiv. Cu(OAc) , acetic acid, reflux, air, 2 d,
3
2
2
3
(
2
2
7
2%; (iii) 4.2 equiv. DDQ, MeOH–H
2
O (10 : 1), rt, 40 min, 79%;
◦
◦
(
iv) 2.5 equiv. BBr
3
, CH
2
Cl
2
, −78 C to −20 C, 20 h, 34%.
Scheme 2 Transformation of clauszoline-K (1) into the clausines C (3), M
(
4) and N (5). Reagents and conditions: (i) 26 equiv. MnO
2
, 4.8 equiv. KCN,
◦
MeOH, rt, 24 h, 100%; (ii) 4.5 equiv. BBr
5
3
, CH
2
Cl
2
, −78 C to rt, 90 min,
2%; (iii) KOH, EtOH–H O (2.3 : 1), reflux, 1 h, 99%.
2
Fig. 2 Molecular structure of 7-methoxy-3-methylcarbazole (10).
stoichiometric amounts of Pd(OAc) (1.2 equiv.) for just 1 h under
2
the conditions of the oxidative cyclization (acetic acid at reflux);
due to decomposition, only 65% of starting material could be
reisolated after this time.
Carbazole 10 was used as a relay compound to 7-oxygenated
carbazole alkaloids (Scheme 1). Oxidation of 10 with 2,3-dichloro-
Fig. 4 Molecular structure of clausine C (clauszoline-L) (3).
5
,6-dicyano-1,4-benzoquinone (DDQ) led to clauszoline-K (1),
which on cleavage of the methyl ether using boron tribromide
afforded 3-formyl-7-hydroxycarbazole (2) (Fig. 3).§
a previously reported route required six steps (40% overall yield)
19
starting from a non-commercial compound. Ether cleavage of
clausine C (3) gave clausine M (4), while saponification of the
ester led to clausine N (5).
Electrophilic bromination of carbazole 10 afforded the 6-
bromocarbazole 11 (Scheme 3; Fig. 5). ꢀ Cleavage of the methyl
ether to 12 and subsequent nickel-mediated coupling using the
Clauszoline-K (1) was transformed quantitatively to clausine
C (clauszoline-L) (3) by treatment with manganese dioxide and
18
potassium cyanide in methanol (Scheme 2; Fig. 4).¶ Our
approach provides clausine C (3) in four steps (57% overall
yield) based on commercial starting materials (7 and 8), while
3
216 | Org. Biomol. Chem., 2006, 4, 3215–3219
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◦
mp: 227–228 C. UV (MeOH): k = 237, 259, 303, 321 (sh) nm. IR
(
1
5
ATR): m = 3397, 2905, 2834, 1610, 1460, 1372, 1338, 1307, 1292,
225, 1196, 1158, 1133, 1104, 1034, 1017, 937, 884, 804, 731, 633,
−
1 1
87 cm . H NMR (500 MHz, acetone-d
6
): d = 2.50 (s, 3 H), 3.89
(
s, 3 H), 6.81 (dd, J = 8.5, 2.2 Hz, 1 H), 7.03 (d, J = 2.2 Hz, 1 H),
.15 (dd, J = 8.2, 1.3 Hz, 1 H), 7.36 (d, J = 8.2 Hz, 1 H), 7.82
m, 1 H), 7.96 (d, J = 8.5 Hz, 1 H), 10.08 (br s, 1 H). C NMR
and DEPT (125 MHz, acetone-d ), 55.65 (CH ),
): d = 21.46 (CH
5.30 (CH), 108.52 (CH), 111.06 (CH), 117.60 (C), 119.95 (CH),
7
(
1
3
6
3
3
9
1
1
1
2
21.44 (CH), 124.39 (C), 126.27 (CH), 128.59 (C), 139.21 (C),
+
42.62 (C), 159.95 (C). MS (EI): m/z = 211 (100) [M ], 210 (15),
+
96 (51), 168 (45), 167 (16). HRMS: m/z calc. for C14
H
13NO [M ]:
11.0997; found: 211.0985. Anal. calc. for C14H13NO: C 79.59, H
Scheme 3 Synthesis of siamenol (6). Reagents and conditions: (i) 1.1 equiv.
6.20, N 6.63; found: C 79.65, H 6.30, N 6.68%.
◦
NBS, CCl
6 h, 100%; (iii) 1. 9.5 equiv. prenyl bromide, 12 equiv. Ni(COD)
rt, 30 min (glove box); 2. 1 equiv. 12, DMF, rt, 6 d, 47%.
4
, reflux, 30 min, 100%; (ii) 2 equiv. BBr
3
, CH
2
Cl
2
, −78 C to rt,
1
2
, DMF,
Clauszoline-K (1)
◦
Light yellow crystals; mp: 183–186 C. UV (MeOH): k = 234, 251
(
2
1
sh), 287, 292, 295, 326 (sh), 344 (sh) nm. IR (ATR): m = 3286,
925, 2808, 2737, 1671, 1609, 1571, 1483, 1412, 1328, 1239, 1200,
−
1
1
161, 1120, 1033, 950, 886, 808, 733, 687, 611 cm . H NMR
): d = 3.93 (s, 3 H), 6.95 (dd, J = 8.6, 2.2 Hz,
(500 MHz, acetone-d
6
1
H), 7.15 (d, J = 2.2 Hz, 1 H), 7.64 (d, J = 8.4 Hz, 1 H), 7.92 (dd,
J = 8.4, 1.6 Hz, 1 H), 8.16 (d, J = 8.6 Hz, 1 H), 8.62 (m, 1 H),
1
1
3
1
7
0.11 (s, 1 H), 10.77 (br s, 1 H). H NMR (500 MHz, CDCl
3
): d =
.90 (s, 3 H), 6.92 (dd, J = 8.5, 2.2 Hz, 1 H), 6.95 (d, J = 2.2 Hz,
H), 7.45 (d, J = 8.4 Hz, 1 H), 7.89 (dd, J = 8.4, 1.5 Hz, 1 H),
.98 (d, J = 8.5 Hz, 1 H), 8.38 (br s, 1 H), 8.49 (m, 1 H), 10.07
Fig. 5 Molecular structure of the 6-bromocarbazole (11).
1
3
(
s, 1 H). C NMR and DEPT (125 MHz, acetone-d
6
): d = 55.79
dimeric p-prenylnickel bromide complex, prepared in situ from
(CH ), 95.93 (CH), 110.09 (CH), 111.75 (CH), 117.52 (C), 122.17
3
2
0
prenyl bromide and bis(1,5-cyclooctadiene)nickel(0), led directly
to siamenol (6). However, the purification of the natural product
proved to be difficult. Pure siamenol (6) was finally obtained
by preparative HPLC of the crude product using a Vydac C8
(CH), 123.45 (CH), 124.39 (C), 126.24 (CH), 130.09 (C), 143.10
(C), 144.74 (C), 160.77 (C), 191.97 (CHO). C NMR and DEPT
1
3
(125 MHz, CDCl ): d = 55.67 (CH ), 95.19 (CH), 109.40 (CH),
3
3
110.58 (CH), 116.90 (C), 121.50 (CH), 122.80 (CH), 123.78 (C),
126.42 (CH), 129.21 (C), 141.38 (C), 143.38 (C), 159.78 (C), 192.03
5
0 mm column (gradient elution with MeCN/H
2
O, from 30 to
+
8
0% MeCN in 25 min). The spectroscopic data of our synthetic
compounds 1–6 (see Experimental section) are in full agreement
with those reported for the corresponding natural products.
(CHO). MS (EI): m/z = 225 (100) [M ], 224 (25), 210 (32), 196
+
(11), 182 (32), 153 (10). HRMS: m/z calc. for C H NO [M ]:
1
4
11
2
6–10
225.0790; found: 225.0787. Anal. calc. for C H NO : C 74.65,
1
4
11
2
In conclusion, via the palladium(II)-catalyzed oxidative cycliza-
tion to 7-methoxy-3-methylcarbazole, we developed a broad access
to a series of 7-oxygenated tricyclic carbazole alkaloids including
the anti-HIV active siamenol (five steps, 34% overall yield). Our
study opens up a simple and direct route to a potential novel class
H 4.92, N 6.22; found: C 74.52, H 4.95, N 6.09%.
3-Formyl-7-hydroxycarbazole (2)
◦
Light yellow crystals; mp > 250 C (decomp.). UV (MeOH): k =
21
of naturally derived anti-HIV agents.
2
3
1
7
6
31, 252 (sh), 287 (sh), 294, 327, 345 (sh) nm. IR (ATR): m = 3326,
231, 2922, 2852, 2752, 1652, 1627, 1602, 1573, 1505, 1488, 1467,
419, 1376, 1327, 1211, 1175, 1157, 1133, 1008, 956, 895, 806, 775,
33, 677, 662, 623 cm . H NMR (500 MHz, acetone-d
.88 (dd, J = 8.4, 2.0 Hz, 1 H), 7.04 (d, J = 2.0 Hz, 1 H), 7.59
Experimental
−1
1
6
): d =
Palladium(II)-catalyzed oxidative cyclization to
-methoxy-3-methylcarbazole (10)
(
d, J = 8.4 Hz, 1 H), 7.89 (dd, J = 8.4, 1.5 Hz, 1 H), 8.08 (d,
J = 8.4 Hz, 1 H), 8.57 (m, 1 H), 8.59 (br s, 1 H), 10.09 (s, 1 H),
10.66 (br s, 1 H). C NMR and DEPT (125 MHz, acetone-d ):
7
1
3
Pd(OAc) (96 mg, 0.43 mmol) and Cu(OAc)
2
2
(1.94 g, 10.68 mmol)
6
were added to a solution of the diarylamine 9 (909 mg, 4.26 mmol)
in glacial acetic acid (45 mL) and the mixture was stirred under
reflux for 2 d in air. After cooling to rt, the black solution was
d = 97.96 (CH), 110.59 (CH), 111.57 (CH), 116.89 (C), 122.21
(CH), 123.10 (CH), 124.64 (C), 126.12 (CH), 129.98 (C), 143.35
(C), 144.72 (C), 158.30 (C), 191.95 (CHO). MS (EI): m/z = 211
+
filtered over a short pad of Celite and silica gel (Et
2
O). Evaporation
(100) [M ], 210 (54), 199 (11), 182 (35), 154 (9). HRMS: m/z calc.
+
of the solvent and flash chromatography (light petroleum ether–
EtOAc, 4 : 1) of the residue on silica gel provided 7-methoxy-
for C13
H
9
NO
2
[M ]: 211.0633; found: 211.0620. Anal. calc. for
C
13
H
9
NO
2
: C 73.92, H 4.29, N 6.63; found: C 74.22, H 4.46, N
3
-methylcarbazole (10), yield: 651 mg (72%). Colorless crystals;
6.32%.
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Clausine C (clauszoline-L) (3)
Siamenol (6)
◦
◦
Light yellow crystals; mp: 195 C. UV (MeOH): k = 217, 238, 248,
Colorless crystals; mp: 132–133 C. UV (MeOH): k = 262, 308,
326 (sh), 338 (sh) nm. IR (ATR): m = 3538, 3388, 2967, 2909,
2853, 1638, 1618, 1584, 1494, 1461, 1375, 1337, 1302, 1255, 1229,
2
1
82, 320 nm. IR (ATR): m = 3273, 2996, 2924, 2836, 1695, 1629,
602, 1581, 1509, 1489, 1467, 1437, 1403, 1324, 1292, 1257, 1191,
−
1
−1
1
1
159, 1135, 1096, 1031, 976, 949, 904, 830, 815, 754, 726, 605 cm .
H NMR (500 MHz, acetone-d
1148, 1113, 1092, 1013, 882, 847, 828, 798, 734 cm . H NMR
(500 MHz, CDCl
1
6
): d = 3.92 (s, 3 H), 3.94 (s, 3 H),
3
): d = 1.81 (s, 3 H), 1.84 (s, 3 H), 2.50 (s, 3 H),
6
.93 (dd, J = 8.6, 2.2 Hz, 1 H), 7.13 (d, J = 2.2 Hz, 1 H), 7.55
3.50 (d, J = 7.1 Hz, 2 H), 5.29 (br s, 1 H), 5.40 (m, 1 H), 6.77
(
8
d, J = 8.5 Hz, 1 H), 8.04 (dd, J = 8.5, 1.6 Hz, 1 H), 8.14 (d, J =
(s, 1 H), 7.13 (d, J = 8.1 Hz, 1 H), 7.21 (d, J = 8.1 Hz, 1 H),
1
1
.6 Hz, 1 H), 8.73 (m, 1 H), 10.64 (br s, 1 H). H NMR (500 MHz,
7.69 (br s, 1 H), 7.72 (s, 1 H), 7.75 (s, 1 H). H NMR (500 MHz,
CDCl
3
): d = 3.89 (s, 3 H), 3.96 (s, 3 H), 6.89 (dd, J = 8.5, 2.2 Hz,
MeOH-d
2 H), 5.50 (m, 1 H), 6.87 (s, 1 H), 7.11 (d, J = 8.1 Hz, 1 H), 7.26
(d, J = 8.1 Hz, 1 H), 7.68 (s, 1 H), 7.71 (s, 1 H). C NMR and
DEPT (125 MHz, CDCl ), 21.42 (CH ), 25.86
): d = 17.91 (CH
(CH ), 30.42 (CH ), 97.24 (CH), 109.92 (CH), 117.15 (C), 119.41
4
): d = 1.84 (s, 6 H), 2.52 (s, 3 H), 3.48 (d, J = 7.4 Hz,
1
H), 6.91 (d, J = 2.2 Hz, 1 H), 7.36 (d, J = 8.5 Hz, 1 H), 7.96 (d,
1
3
J = 8.5 Hz, 1 H), 8.05 (dd, J = 8.5, 1.6 Hz, 1 H), 8.27 (br s, 1 H),
1
3
8
5
1
1
.69 (m, 1 H). C NMR and DEPT (125 MHz, acetone-d
6
): d =
3
3
3
1.89 (CH ), 55.75 (CH ), 95.75 (CH), 109.75 (CH), 111.01 (CH),
17.51 (C), 121.78 (C), 122.02 (CH), 122.16 (CH), 123.98 (C),
3
3
3
2
(CH), 120.83 (CH), 122.59 (CH), 123.67 (C), 125.67 (C), 125.67
26.56 (CH), 142.99 (C), 143.80 (C), 160.60 (C), 167.97 (C=O).
(CH), 128.59 (C), 134.71 (C), 137.72 (C), 139.86 (C), 153.64 (C).
1
3
13
C NMR and DEPT (125 MHz, CDCl
3
): d = 51.94 (CH
3
), 55.63
C NMR and DEPT (125 MHz, MeOH-d
4
): d = 17.88 (CH
3
),
(
(
(
(
CH
3
), 95.01 (CH), 108.97 (CH), 109.83 (CH), 117.04 (C), 121.36
21.54 (CH
3
), 26.03 (CH ), 29.69 (CH ), 97.08 (CH), 110.84 (CH),
3
2
CH), 121.43 (C), 121.89 (CH), 123.28 (C), 126.27 (CH), 141.27
117.25 (C), 119.65 (CH), 120.87 (CH), 121.63 (C), 125.01 (C),
125.11 (CH), 125.84 (CH), 128.47 (C), 132.24 (C), 139.60 (C),
C), 142.33 (C), 159.50 (C), 167.97 (C=O). MS (EI): m/z = 255
+
+
100) [M ], 240 (23), 225 (20), 224 (44), 213 (23), 212 (21), 196 (16),
141.57 (C), 155.31 (C). MS (EI): m/z = 265 (77) [M ], 250 (25),
+
1
83 (9), 181 (9). HRMS: m/z calc. for C15
H
13NO
3
[M ]: 255.0895;
248 (26), 210 (100), 209 (38), 197 (69), 196 (48), 180 (12), 167 (12).
+
found: 255.0907. Anal. calc. for C15
H
13NO
3
: C 70.58, H 5.13, N
HRMS: m/z calc. for C18
H
19NO [M ]: 265.1467; found: 265.1472.
5
.49; found: C 70.70, H 5.50, N 5.34%.
Acknowledgements
Clausine M (4)
This work was supported by JADO Technologies, Dresden. We
are grateful to Dr. Georg Schlechtingen (JADO Technologies,
Dresden) for his help in the preparative HPLC.
◦
Light yellow crystals; mp: 220–222 C. UV (MeOH): k = 219 (sh),
2
39 (sh), 247, 283, 309 (sh), 318 (sh) nm. IR (ATR): m = 3369,
2
7
958, 2929, 2860, 1733, 1610, 1462, 1380, 1269, 1171, 1135, 1074,
−
1
1
69, 743, 604 cm . H NMR (500 MHz, acetone-d
6
): d = 3.94 (s,
3
H), 6.87 (dd, J = 8.4, 2.1 Hz, 1 H), 7.02 (d, J = 2.1 Hz, 1 H),
Notes and references
7
.52 (d, J = 8.5 Hz, 1 H), 8.01 (dd, J = 8.5, 1.6 Hz, 1 H), 8.07 (d,
‡
Crystal data for 10: C14
P2
1056.1(4) A
H
13NO, M = 211.25, monoclinic, space group:
1
3
◦
J = 8.4 Hz, 1 H), 8.59 (s, 1 H), 8.69 (m, 1 H), 10.55 (br s, 1 H).
C
˚
1
/c, a = 22.924(3), b = 5.787(1), c = 8.020(1) A, b = 96.98(3) , V =
˚
3
, Z = 4, D = 1.329 g cm−3, l = 0.084 mm−1, T = 198(2)
NMR and DEPT (125 MHz, acetone-d
6
): d = 51.87 (CH
3
), 97.79
c
◦
K, k = 0.71073 A˚ , h range: 3.58–25.40 , 13562 reflections measured, 1915
(
(
(
2
2
CH), 110.30 (CH), 110.85 (CH), 116.90 (C), 121.64 (C), 121.90
CH), 122.04 (CH), 124.23 (C), 126.36 (CH), 143.27 (C), 143.79
independent (Rint = 0.0280), 151 parameters. The structure was solved
2
by direct methods and refined by full-matrix least-squares on F ; final R
+
C), 158.14 (C), 168.03 (C=O). MS (EI): m/z = 241 (100) [M ],
indices for 1618 observed reflections [I > 2r(I)]: R
1
= 0.0457, wR = 0.1179;
2
+
˚
−3
10 (50), 182 (22), 153 (6). HRMS: m/z calc. for C14
H
11NO
3
[M ]:
maximal residual electron density: 0.674 e A . CCDC reference number
09679. For crystallographic data in CIF or other electronic format see
DOI: 10.1039/b607792g.
Crystal data for 2: C13
P2
6
41.0739; found: 241.0765.
§
H
9
NO
2
, M = 211.21, monoclinic, space group:
◦
Clausine N (5)
1
/n, a = 7.381(1), b = 11.493(1), c = 11.058(1) A˚ , b = 95.02(1) , V =
3
−3
−1
9
34.45(17) A˚ , Z = 4, D
c
= 1.501 g cm , l = 0.103 mm , T = 198(2)
◦
◦
Light yellow crystals; mp > 264 C (decomp.). UV (MeOH): k =
K, k = 0.71073 A˚ , h range: 3.29–30.00 , 25734 reflections measured, 2704
independent (Rint = 0.0442), 153 parameters. The structure was solved
2
2
1
7
3
1
8
37 (sh), 247, 278, 307 (sh), 319 nm. IR (ATR): m = 3385, 2921,
851, 1666, 1606, 1579, 1505, 1485, 1464, 1436, 1413, 1341, 1320,
294, 1262, 1188, 1151, 1123, 1096, 1028, 942, 897, 813, 765, 752,
2
by direct methods and refined by full-matrix least-squares on F ; final R
indices for 2059 observed reflections [I > 2r(I)]: R
1
= 0.0414, wR = 0.1062;
2
˚
−3
maximal residual electron density: 0.364 e A . CCDC reference number
609677. For crystallographic data in CIF or other electronic format see
DOI: 10.1039/b607792g.
−
1
1
23, 683, 620, 591 cm . H NMR (500 MHz, acetone-d
6
): d =
.92 (s, 3 H), 6.93 (dd, J = 8.6, 2.2 Hz, 1 H), 7.13 (d, J = 2.2 Hz,
H), 7.56 (d, J = 8.5 Hz, 1 H), 8.07 (dd, J = 8.5, 1.6 Hz, 1 H),
¶
Crystal data for 3: C15
H
13NO
3
, M = 255.26, triclinic, space group: P1,
a = 8.118(3), b = 9.020(2), c = 9.143(3) A˚ , a = 101.10(2), b = 102.27(3), c =
1
3
◦
3
−3
−1
.30 (d, J = 8.6 Hz, 1 H), 8.77 (d, J = 1.6 Hz, 1 H). C NMR
104.33(3) , V = 612.2(4) A˚ , Z = 2, D = 1.385 g cm , l = 0.097 mm
,
c
◦
˚
, h range: 3.03–25.40 , 14687 reflections
and DEPT (125 MHz, acetone-d
6
): d = 55.75 (CH
3
), 95.68 (CH),
T = 198(2) K, k = 0.71073 A
measured, 2242 independent (Rint = 0.0536), 178 parameters. The structure
1
1
1
09.71 (CH), 110.89 (CH), 117.51 (C), 121.92 (C), 122.00 (CH),
was solved by direct methods and refined by full-matrix least-squares
22.50 (CH), 123.92 (C), 126.89 (CH), 142.84 (C), 143.68 (C),
2
on F ; final R indices for 1792 observed reflections [I > 2r(I)]: R
1
=
+
−3
60.55 (C), 168.44 (C=O). MS (EI): m/z = 241 (76) [M ], 226
0.0450, wR2 = 0.1141; maximal residual electron density: 0.169 e A˚
.
(
28), 211 (8), 198 (27), 111 (44), 97 (63), 71 (69), 57 (100). HRMS:
CCDC reference number 609678. For crystallographic data in CIF or
other electronic format see DOI: 10.1039/b607792g.
+
m/z calc. for C14
H
11NO
3
[M ]: 241.0739; found: 241.0748. Anal.
: C 69.70, H 4.60, N 5.81; found: C 69.84, H
ꢀ
Crystal data for 11: C14
P2
, a = 6.642(1), b = 7.761(1), c = 11.984(5) A, b = 105.13(3) , V =
596.3(3) A˚ , Z = 2, D
= 1.616 g cm , l = 3.428 mm , T = 198(2) K,
H
12BrNO, M = 290.16, monoclinic, space group:
◦
˚
calc. for C14
H
11NO
3
1
3
−3
−1
4.62, N 5.84%.
c
3
218 | Org. Biomol. Chem., 2006, 4, 3215–3219
This journal is © The Royal Society of Chemistry 2006

View Article Online
◦
k = 0.71073 A˚ , h range: 3.16–30.00 , 16713 reflections measured, 3380
13 B. A˚ kermark, L. Eberson, E. Jonsson and E. Petersson, J. Org. Chem.,
independent (Rint = 0.0289), 160 parameters. The structure was solved
1975, 40, 1365; R. B. Miller and T. Moock, Tetrahedron Lett., 1980,
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2
by direct methods and refined by full-matrix least-squares on F ; final
R indices for 3122 observed reflections [I > 2r(I)]: R
1
= 0.0220, wR =
2
0
.0440; absolute structure (Flack parameter): v = −0.005(6), maximal
14 H.-J. Kn o¨ lker and N. O’Sullivan, Tetrahedron, 1994, 50, 10893; H.-J.
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residual electron density: 0.230 e A˚ . CCDC reference number 609680.
For crystallographic data in CIF or other electronic format see DOI:
−3
1
0.1039/b607792g.
2
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2
3
16 Compound 9 has been prepared previously in lower yield, see: S.
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