Novel approach to biscarbazole alkaloids via Ullmann coupling - Synthesis of murrastifoline - A and bismurrayafoline - A

Article abstract of DOI:10.1039/c2ob26229k

Unprecedented Ullmann couplings of murrayafoline-A with either 6-bromo- or 4-bromocarbazole derivatives provide highly efficient synthetic routes to the biscarbazole alkaloids murrastifoline-A (6 steps, 66% overall yield) and bismurrayafoline-A (6 steps, 28% overall yield).

Full text of DOI:10.1039/c2ob26229k

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COMMUNICATION
Novel approach to biscarbazole alkaloids via Ullmann coupling – synthesis
of murrastifoline-A and bismurrayafoline-A†‡
Carsten Börger, Olga Kataeva and Hans-Joachim Knölker*
Received 27th June 2012, Accepted 24th July 2012
DOI: 10.1039/c2ob26229k
Unprecedented Ullmann couplings of murrayafoline-A with
either 6-bromo- or 4-bromocarbazole derivatives provide
highly efficient synthetic routes to the biscarbazole alkaloids
murrastifoline-A (6 steps, 66% overall yield) and bismurraya-
foline-A (6 steps, 28% overall yield).
Carbazole alkaloids exhibit a broad variety of useful biological
activities (e.g. anti-tumour, antibiotic, anti-viral, anti-inflamma-
tory and anti-malarial) which has led to the development of
many synthetic routes to carbazoles.1,2 We have described
efficient iron-mediated and palladium-catalysed syntheses of car-
bazoles.3,4 Biscarbazole alkaloids are interesting because of their
structural characteristics. However, due to the low natural abun-
dance of biscarbazole alkaloids and the still limited synthetic
access, there is only scant knowledge of their bioactivity.1,5,6
Therefore, we are seeking to develop new synthetic routes
to biscarbazoles. Herein, we describe
a novel synthetic
approach to murrastifoline-A and bismurrayafoline-A using an
Ullmann coupling for the construction of the biscarbazole
linkage.
Fig. 1 Murrastifoline-A (1), murrastifoline-F (2), bismurrayafoline-A (3)
and the 1-methoxycarbazole alkaloids 4a–e.
In 1990, Furukawa et al. reported the isolation of the N-aryl
linked biscarbazole alkaloid murrastifoline-A (1) from the root
bark of Murraya euchrestifolia Hayata (Fig. 1).7 A synthesis of
murrastifoline-A (1) has been described by Chida et al. in 2005
via a twofold Buchwald–Hartwig amination as the key step
(9 steps and 23% overall yield).8 Three years after the isolation
of murrastifoline-A (1), Furukawa et al. isolated murrastifoline-F
(2) from the root and stem bark of Murraya koenigii (L.)
Spreng.9 In 2001, Bringmann et al. described the first total syn-
thesis of murrastifoline-F (2) by oxidation of murrayafoline-A
(4a) with lead(IV) acetate and the separation and assignment of
the absolute configuration of the atropisomers.10 In 1983, Furu-
kawa et al. isolated bismurrayafoline-A (3) from Murraya
euchrestifolia Hayata.11 In 2001, Bringmann and co-workers
reported the formation of bismurrayafoline-A (3) in up to 19%
yield as a by-product of the reduction of mukonine (4e) with
lithium aluminium hydride (9% yield of 3 over seven steps from
commercially available compounds).12
The monomeric carbazole units of the biscarbazole alkaloids
have also been found as natural products. In 1978, Chakraborty
and co-workers described the isolation of mukonine (4e) from
Murraya koenigii.13 In the late nineties, Wu et al. isolated
mukonine (4e) from the stem bark and the root bark of Clausena
excavata.14 In 1983, the parent compound of the 1-methoxycar-
bazole alkaloids, murrayafoline-A (4a), was obtained for the first
time from the root bark of Murraya euchrestifolia Hayata by Fur-
ukawa et al.15,16 Further isolations of murrayafoline-A (4a) have
been reported in the following years from the roots of Murraya
crenulata (Turz.) Oliver,17 the root and stem bark of Murraya
koenigii (L.) Spreng9,18 and the root and stem bark of Clausena
excavata.14b In 1990, we described an iron-mediated total syn-
thesis of mukonine (4e),19 which has been significantly
improved later on.20,21 Several alternative methods for the
synthesis of mukonine (4e) have been reported.13,22 Very
Department Chemie, Technische Universität Dresden, Bergstrasse 66,
01069 Dresden, Germany. E-mail: hans-joachim.knoelker@tu-dresden.de;
Fax: +49 351-463-37030
†Part 103 of Transition Metals in Organic Synthesis; for Part 102, see
ref. 21.
‡Electronic supplementary information (ESI) available: 1H and 13C
NMR data of compounds 1, 3, 4a, 9 and 12. CCDC 883858. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c2ob26229k
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Scheme 2 Synthesis of murrayafoline-A (4a) and the 6-bromocarba-
zole 9. Reagents and conditions: (a) 6 mol% Pd(OAc)2, 12 mol%
SPhos, 1.1 equiv. PhBr, 1.4 equiv. Cs2CO3, toluene, reflux, 40 h, 100%;
(b) 0.1 equiv. Pd(OAc)2, 0.1 equiv. K2CO3, PivOH, 115 °C, 14 h, 91%;
(c) 3 equiv. LiAlH4, Et2O, CH2Cl2, rt, 4.5 h, 87%; (d) 1.04 equiv. NBS,
MeCN, rt, 3 h; (e) 6.8 equiv. NaH, 3.4 equiv. TsCl, THF, 0 °C to rt,
16 h, 95% (two steps).
Scheme 1 Retrosynthetic analysis of murrastifoline-A (1).
recently, we have described the best current approach to muko-
nine (4e) (2 steps, 91% overall yield).21 A range of different
approaches to murrayafoline-A (4a) has been reported.12,20a,22b,g,23
We decided to use murrayafoline-A (4a) and the 6-functiona-
lised N-protected mukonine derivative 5 as key intermediates for
our projected synthesis of murrastifoline-A (1) (Scheme 1). Both
murrayafoline-A (4a)22b and carbazole 5 should be available
from mukonine (4e) which can be prepared from methyl
4-amino-3-methoxybenzoate (6).21
Buchwald–Hartwig coupling of the commercially available
arylamine 6 and bromobenzene followed by palladium(II)-
catalysed oxidative cyclisation of the diarylamine 7 afforded
mukonine (4e) (Scheme 2).21,22g Reduction of 4e with lithium
aluminium hydride provided murrayafoline-A (4a) which was
structurally confirmed by its spectroscopic data.§ Using the
present route, murrayafoline-A (4a) is available in three steps
and 79% overall yield.
Bromination of mukonine (4e) by slow addition of N-bromo-
succinimide in acetonitrile at room temperature provided methyl
6-bromo-1-methoxy-9H-carbazole-3-carboxylate (8) (Scheme 2).
Subsequent protection of the nitrogen atom by reaction with
para-toluenesulfonyl chloride led to the 6-bromo-9-tosylcarba-
zole 9.
Scheme 3 Synthesis of murrastifoline-A (1). Reagents and conditions:
(a) 1 equiv. 9, 3 equiv. 4a, 1 equiv. Cu, 2.5 equiv. K2CO3, nitrobenzene,
170 °C, 112 h, 76%; (b) 20 equiv. LiAlH4, Et2O, CH2Cl2, rt, 17 h,
100%.
With the readily available carbazoles 9 and 4a in hand, we
envisaged direct access to murrastifoline-A (1). In a model study,
an attempted Buchwald–Hartwig coupling of mukonine (4e) and
a 6-bromocarbazole [cat. Pd(OAc)2, cat. BINAP, Cs2CO3 or
K2CO3, toluene, reflux]24 failed. Using Ullmann conditions as
reported for the synthesis of oligomer- and polymer-bound car-
bazoles,25 coupling of murrayafoline-A (4a) with the 6-bromo-
carbazole 9 provided the biscarbazole 10 in 76% yield
(Scheme 3).§ Reduction of compound 10 using an excess of
lithium aluminium hydride with concomitant removal of the
tosyl protecting group afforded directly murrastifoline-A (1) (6
steps and 66% overall yield based on 6). The spectroscopic data
of murrastifoline-A (1) are in good agreement with those
reported in the literature.§7
Reaction of murrastifoline-A (1) with (R)-(−)-α-methoxy-
α-(trifluoromethyl)phenylacetyl chloride led to the correspond-
ing (S)-amide.26 We performed several NMR experiments with
the murrastifoline-A-(S)-Mosher amide to gather information on
the conformational stability of the atropisomers. At room temp-
erature, we observed only one set of signals, whereas at −10 °C,
signals corresponding to four diastereoisomers could be
detected. Thus, we concluded that racemisation of murrastifo-
line-A (1) occurs very rapidly at room temperature. Unfortu-
nately, the activation energy for the rotation about the C–N bond
of 1 could not be determined due to the additional presence of
isomers resulting from hindered rotation of the amide bond.27
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Scheme 4 Synthesis of tert-butyl 4-bromo-1-methoxy-3-methyl-9H-
carbazole-9-carboxylate (12). Reagents and conditions: (a) 1.03 equiv.
NBS, MeCN, rt, 4 h; (b) 2 equiv. Boc2O, 1 equiv. DMAP, MeCN, rt,
20 h, 99% (two steps).
Scheme 5 Synthesis of bismurrayafoline-A (3). Reagents and con-
ditions: (a) 1 equiv. 12, 3 equiv. 4a, 1 equiv. Cu, 2.5 equiv. K2CO3,
nitrobenzene, 200 °C, 7 d, 36%.
Table 1 Synthesis of bismurrayafoline-A (3)a
Entry
4a
12
Cu
3, Yield
4a, Yieldb
1
2
3
4
3 equiv.
3 equiv.
1 equiv.
—
1 equiv.
1 equiv.
—
1 equiv.
—
1 equiv.
1 equiv.
36
—
2
61
87c
80
—
1 equiv.
Decomp.
a All reactions in nitrobenzene with 2.5 equiv. K2CO3 at 200 °C for 7 d.
b Re-isolated starting material. c Additionally 62% of 12 were re-isolated.
assignment for bismurrayafoline-A (3) is based on the spectro-
scopic data,k which are in full agreement with those reported in
the literature,11 and has been additionally supported by 2D-NMR
experiments (ESI‡).
The mechanism of this unprecedented rearrangement leading
to functionalisation of a carbazole 3-methyl group is intriguing.
In the absence of copper, no product was obtained and the start-
ing material could be re-isolated almost quantitatively even after
seven days at 200 °C (Table 1, entry 2). Reaction of murrayafo-
line-A (4a) using the optimised conditions but without the 4-bro-
mocarbazole 12 led to bismurrayafoline-A (3) in only 2% yield
along with large amounts of starting material (entry 3). This
result indicated that a copper-mediated oxidative dimerisation of
murrayafoline-A (4a) contributes only insignificantly to the for-
mation of bismurrayafoline-A (3). Heating of the 4-bromocarba-
zole 12 under Ullmann coupling conditions in the absence of
murrayafoline-A (4a) resulted in complete decomposition of the
starting material (entry 4).
Obviously, bismurrayafoline-A (3) is generated via two inde-
pendent mechanistic pathways. It is assumed that the oxidative
coupling of two molecules of murrayafoline-A (4a) to bismurraya-
foline-A (3) may be induced by the solvent nitrobenzene29 or by
traces of air. The major mechanistic pathway is proposed to
proceed via initial oxidative addition of bromocarbazole 12 to a
copper(I) salt generating the aryl copper(III) species 13 as
suggested for the classical Ullmann coupling (Scheme 6).30 Sub-
sequent elimination of hydrobromic acid activates a C–H bond
of the methyl group and generates the metallacycle 14. Copper-
Fig. 2 Molecular structure of tert-butyl 4-bromo-1-methoxy-3-methyl-
9H-carbazole-9-carboxylate (12) in the crystal.
We envisaged a similar strategy for the synthesis of murrasti-
foline-F (2). Bromination of the electron-rich A-ring of murraya-
foline-A (4a) was expected to take place at C-4.28 In fact,
reaction of murrayafoline-A (4a) with N-bromosuccinimide in
acetonitrile provided exclusively the 4-bromo derivative 11
(Scheme 4). Protection of the nitrogen atom using di-tert-butyl
dicarbonate led to tert-butyl 4-bromo-1-methoxy-3-methyl-9H-
carbazole-9-carboxylate (12). The structure of compound 12 has
been unequivocally confirmed by an X-ray crystal structure
determination (Fig. 2).¶
However, coupling of murrayafoline-A (4a) and the N-Boc
protected 4-bromocarbazole 12 using the same reaction con-
ditions as described above afforded bismurrayafoline-A (3),
instead of the expected murrastifoline-F (2) (Scheme 5). At
temperatures of 200 °C, the Boc protecting group is removed.3d
Optimisation of this novel rearrangement led to bismurraya-
foline-A (3) in up to 36% yield (Table 1, entry 1). The structural
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Notes and references
§Spectroscopic data for murrayafoline-A (4a): Colourless crystals, mp
54–54.5 °C (ref. 16a: 52–53 °C); UV (MeOH): λ = 221, 226, 240, 243,
251 (sh), 259 (sh), 281 (sh), 291, 316 (sh), 328, 341 nm; IR (ATR):
ν = 3414, 3054, 2917, 2848, 1616, 1587, 1543, 1502, 1450, 1391, 1333,
1303, 1278, 1261, 1228, 1186, 1133, 1104, 1036, 1011, 942, 826, 766,
746, 730, 671, 640 cm−1 1H NMR (500 MHz, CDCl3): δ = 2.54 (s,
;
3 H), 4.00 (s, 3 H), 6.74 (s, 1 H), 7.20 (ddd, J = 8.0 Hz, 6.9 Hz, 1.3 Hz,
1 H), 7.39 (ddd, J = 8.2 Hz, 6.9 Hz, 1.2 Hz, 1 H), 7.44 (dt, J = 8.1 Hz,
0.9 Hz, 1 H), 7.48 (s, 1 H), 8.02 (d, J = 7.8 Hz, 1 H), 8.16 (br s, 1 H);
13C NMR and DEPT (125 MHz, CDCl3): δ = 22.08 (CH3), 55.61
(CH3), 107.77 (CH), 111.03 (CH), 112.63 (CH), 119.27 (CH), 120.59
(CH), 123.64 (C), 124.42 (C), 125.63 (CH), 128.08 (C), 129.58 (C),
139.56 (C), 145.44 (C); MS (EI): m/z (%) = 211 (M+, 100), 196 (83),
180 (9), 168 (62), 167 (60), 166 (13), 152 (6), 140 (7), 139 (10), 106
(6), 84 (7); anal. calc. for C14H13NO: C 79.59, H 6.20, N 6.63; found:
C 79.73, H 6.48, N 6.75.
Experimental procedure for the Ullmann coupling of murraya-
foline-A (4a) with the 6-bromocarbazole 9 to the biscarbazole 10:
A mixture of murrayafoline-A (4a) (57.2 mg, 0.271 mmol), 6-bromo-
carbazole
9 (44.1 mg, 0.090 mmol), copper bronze (6.2 mg,
0.098 mmol) and potassium carbonate (31.2 mg, 0.226 mmol) in
nitrobenzene (5 mL) was heated at 170 °C for 112 h. After cooling to
room temperature, the reaction mixture was filtered over magnesium
sulfate (ethyl acetate). Removal of the solvent and flash chromato-
graphy (gradient elution with petroleum ether–ethyl acetate, 49 : 1 to
1 : 1) on silica gel provided the biscarbazole 10 (42.2 mg, 76%) as col-
ourless crystals; mp 120.5–121 °C. UV (MeOH): λ = 225 (sh), 243,
268 (sh), 290, 330, 344 (sh) nm; IR (ATR): ν = 3341, 3058, 2998,
2934, 2840, 1711, 1653, 1633, 1581, 1499, 1451, 1403, 1325, 1285,
1242, 1221, 1175, 1156, 1122, 1095, 1035, 981, 953, 912, 875, 812,
1
767, 745, 703, 682, 661, 632 cm−1; H NMR (600 MHz, CDCl3): δ =
2.44 (s, 3 H), 2.57 (s, 3 H), 3.64 (s, 3 H), 3.82 (s, 3 H), 3.92 (s, 3 H),
6.77 (d, J = 0.8 Hz, 1 H), 7.23–7.25 (m, 1 H), 7.25–7.28 (m, 1 H),
7.32 (d, J = 7.9 Hz, 2 H), 7.36 (ddd, J = 8.4 Hz, 7.3 Hz, 1.0 Hz, 1 H),
7.59–7.60 (m, 2 H), 7.63 (d, J = 1.1 Hz, 1 H), 7.86 (d, J = 8.3 Hz, 2
H), 8.05 (d, J = 2.3 Hz, 1 H), 8.09 (dd, J = 7.9 Hz, 1.1 Hz, 1 H), 8.21
(d, J = 1.1 Hz, 1 H), 8.50 (d, J = 9.0 Hz, 1 H); 13C NMR and DEPT
(150 MHz, CDCl3): δ = 21.82 (CH3), 21.90 (CH3), 52.46 (CH3),
55.90 (CH3), 56.03 (CH3), 109.93 (CH), 110.20 (CH), 111.67 (CH),
112.92 (CH), 114.78 (CH), 116.44 (CH), 116.76 (CH), 119.95 (CH),
120.35 (CH), 120.53 (C), 123.51 (C), 125.69 (C), 125.94 (CH),
126.18 (C), 126.81 (2 CH), 127.18 (CH), 128.32 (C), 129.54 (2 CH),
130.33 (C), 131.94 (C), 136.18 (C), 138.51 (C), 140.05 (C), 142.63
(C), 143.06 (C), 144.43 (C), 146.74 (C), 148.27 (C), 166.81 (CvO);
ESI-MS: 619 [M + H]+.
Spectroscopic data for murrastifoline-A (1): Colourless crystals, mp
174 °C (ref. 7: oil); UV (MeOH): λ = 226, 243, 253 (sh), 262 (sh), 292,
334, 346 nm; IR (ATR): ν = 3419, 3317, 2921, 2852, 1582, 1502, 1484,
1453, 1375, 1329, 1311, 1285, 1223, 1141, 1115, 1094, 1033, 1015,
977, 944, 910, 827, 801, 764, 746, 667, 633 cm−1; 1H NMR (500 MHz,
acetone-d6): δ = 2.48 (s, 3 H), 2.51 (s, 3 H), 3.56 (s, 3 H), 4.02 (s, 3 H),
6.84 (s, 1 H), 6.87 (s, 1 H), 7.15 (dt, J = 8.5 Hz, 0.9 Hz, 1 H), 7.20
(ddd, J = 7.9 Hz, 6.9 Hz, 0.9 Hz, 1 H), 7.32 (ddd, J = 8.2 Hz, 7.3 Hz,
1.3 Hz, 1 H), 7.40 (dd, J = 8.5 Hz, 1.9 Hz, 1 H), 7.54 (s, 1 H), 7.62 (dd,
J = 1.4 Hz, 0.8 Hz, 1 H), 7.66 (d, J = 8.5 Hz, 1 H), 8.09 (dd, J = 2.2
Hz, 0.6 Hz, 1 H), 8.12 (dt, J = 7.9 Hz, 0.9 Hz, 1 H), 10.45 (br s, 1 H);
13C NMR and DEPT (125 MHz, acetone-d6): δ = 21.72 (CH3), 21.93
(CH3), 55.87 (CH3), 56.09 (CH3), 108.77 (CH), 110.75 (CH), 111.06
(CH), 111.71 (CH), 113.36 (CH), 113.41 (CH), 120.16 (CH), 120.53
(CH), 120.75 (CH), 123.86 (C), 123.98 (C), 125.07 (C), 126.00 (C),
126.43 (CH), 126.58 (CH), 129.90 (C), 129.97 (C), 130.10 (C), 130.40
(C), 132.00 (C), 139.99 (C), 144.01 (C), 146.70 (C), 147.77 (C); MS
(EI): m/z (%) = 420.3 (M+, 100), 406.2 (11), 405.2 (7), 391.1 (6), 390.2
(16), 375.2 (5), 374.2 (8); HRMS: m/z calc. for C28H24N2O2 (M+):
420.1838; found: 420.1823.
Scheme 6 Proposed mechanism for the formation of bismurraya-
foline-A (3).
mediated C–H bond activations have been described pre-
viously.31 Addition of murrayafoline-A (4a) to intermediate 14
via ring opening leads to the copper(III) complex 15. Finally,
reductive elimination provides bismurrayafoline-A (3) and regen-
erates the copper catalyst.
Conclusions
Following our optimised route, murrayafoline-A (4a) has been
prepared in three steps and 79% overall yield which currently
represents the best route to this alkaloid. Using mukonine (4e)
and murrayafoline-A (4a) as building blocks, we have achieved
a highly efficient total synthesis of murrastifoline-A (1) (six
steps and 66% overall yield starting from commercially available
compounds). The key-step of our approach is an Ullmann coup-
ling of murrayafoline A (4a) with a 6-bromocarbazole derivative.
Moreover, an unprecedented rearrangement in the course of a
copper-mediated coupling of murrayafoline-A (4a) and a
4-bromo-3-methylcarbazole derivative opened up a novel route
to bismurrayafoline-A (3) (six steps and 28% overall yield). Both
of our synthetic approaches are much superior to those pre-
viously reported for biscarbazole alkaloids.
¶Crystal data for tert-butyl 4-bromo-1-methoxy-3-methyl-9H-carbazole-
9-carboxylate (12): C19H20BrNO3, crystal size: 0.26 × 0.11 × 0.03 mm3,
M = 390.27 g mol−1, monoclinic, space group P21/n, λ = 0.71073 Å,
a = 8.8228(3), b = 20.4039(7), c = 9.9068(4) Å, β = 106.586(2)°, V =
1709.21(11) Å3, Z = 4, ρc = 1.517 g cm−3, μ = 2.422 mm−1, T = 150(2)
K, θ range = 2.00° to 28.48°, reflections collected: 20 882, independent:
4197 (Rint = 0.0803). The structure was solved by direct methods and
refined by full-matrix least-squares on F2; R1 = 0.0335; wR2 = 0.0693
Acknowledgements
We thank Dr. M. Gruner (TU Dresden) for 2D-NMR experi-
ments and the Deutsche Forschungsgemeinschaft for financial
support (grant KN 240/16-1).
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[I > 2σ(I)]; maximal residual electron density: 0.971 e Å−3. CCDC
883858.
14 (a) T.-S. Wu, S.-C. Huang, P.-L. Wu and C.-M. Teng, Phytochemistry,
1996, 43, 133; (b) T.-S. Wu, S.-C. Huang, P.-L. Wu and C.-S. Kuoh,
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kSpectroscopic data for bismurrayafoline-A (3): colourless crystals, mp
209.5–210 °C from petroleum ether–EtOAc (ref. 11: 176–177 °C from
Et2O); UV (MeOH): λ = 224, 243, 251, 262 (sh), 282, 292, 323 (sh),
338, 352 (sh) nm; IR (ATR): ν = 3434, 3051, 3015, 2965, 2927, 2843,
1727, 1626, 1582, 1542, 1502, 1451, 1393, 1341, 1299, 1258, 1227,
1211, 1146, 1119, 1104, 1037, 1012, 942, 827, 764, 746, 730, 657, 640,
618 cm−1; 1H NMR (500 MHz, CDCl3): δ = 2.52 (s, 3 H), 3.80 (s, 3 H),
3.91 (s, 3 H), 5.97 (s, 2 H), 6.77 (d, J = 0.6 Hz, 1 H), 6.77 (d, J = 0.9
Hz, 1 H), 7.11–7.18 (m, 2 H), 7.31–7.36 (m, 2 H), 7.36–7.43 (m, 2 H),
7.48 (s, 1 H), 7.53 (s, 1 H), 7.91 (d, J = 7.9 Hz, 1 H), 8.03 (d, J = 7.9
Hz, 1 H), 8.14 (br s, 1 H); 13C NMR and DEPT (125 MHz, CDCl3): δ =
21.85 (CH3), 49.59 (CH2), 55.53 (CH3), 55.89 (CH3), 105.10 (CH),
109.28 (CH), 109.84 (CH), 110.93 (CH), 111.03 (CH), 112.92 (CH),
118.93 (CH), 119.36 (CH), 120.27 (CH), 120.70 (CH), 123.29 (C),
123.62 (C), 124.15 (C), 125.11 (C), 125.65 (CH), 125.74 (CH), 128.55
(C), 129.02 (C), 129.21 (C), 131.48 (C), 139.48 (C), 141.53 (C), 145.76
(C), 146.80 (C); MS (EI): m/z (%) = 420.2 (M+, 40), 211.1 (39), 210.2
(100), 196.1 (6), 180.1 (5), 167.1 (14); HRMS: m/z calc. for
19 H.-J. Knölker and M. Bauermeister, J. Chem. Soc., Chem. Commun.,
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