Synthesis and resolution of BICOL, a carbazole analogue of BINOL

Article abstract of DOI:10.1002/1099-0690(200206)2002:12<1952::AID-EJOC1952>3.0.CO;2-L

The synthesis and resolution of a novel chiral C₂-symmetric bicarbazolediol (BICOL), is reported. The key step in the synthesis is the copper(II)-catalysed oxidative phenol coupling of 3-hydroxycarbazole. Menthyl chloroformate is used as resolv

Full text of DOI:10.1002/1099-0690(200206)2002:12<1952::AID-EJOC1952>3.0.CO;2-L

FULL PAPER
Synthesis and Resolution of BICOL, a Carbazole Analogue of BINOL
[
a]
[a]
[a]
[a]
[a]
Peter N. M. Botman, Martijn Postma, Jan Fraanje, Kees Goubitz, Henk Schenk,
[a]
[a]
Jan H. van Maarseveen, and Henk Hiemstra*
Keywords: Oxidative phenol coupling / Chiral auxiliaries / Atropisomerism / Chiral resolution
The synthesis and resolution of a novel chiral C
2
-symmetric
solving agent for the separation of the two enantiomers of BI-
bicarbazolediol (BICOL), is reported. The key step in the syn-
thesis is the copper(II)-catalysed oxidative phenol coupling
of 3-hydroxycarbazole. Menthyl chloroformate is used as re-
COL.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
Over the last few decades C -symmetric bidentate ligands
2
have proven to be very efficient chiral sources in homogen-
eous asymmetric catalysis.[ The success of complexes of
1]
2,2Ј-disubstituted 1,1Ј-binaphthyls, in particular BINOL 2
and BINAP 3, in giving high enantioselectivities in numer-
ous catalytic reactions, has encouraged the synthesis of sev-
[
2]
eral related ligands. In order to control and optimise the
chiral induction, electronic and steric factors were varied
widely. In this regard, we recently developed the synthesis
of BIFOL 4, BIFAP 5 and BIFAPS 6, a family of new bi-
dentate ligands based on the bidibenzofuran backbone and
useful for asymmetric catalysis in both organic solvents and
[
3]
in aqueous media. The promising results of these ligands
in asymmetric catalysis led to the idea of the synthesis of ylhydrazine hydrochloride, was oxidised to methoxycarb-
BICOL 1, another new chiral bidentate ligand based on the azole 8 using wet palladium on carbon in a high boiling
bicarbazole backbone. In addition to the successful bidi- solvent (p-cymene, b.p. 176Ϫ178 °C). Deactivation of the
benzofuran type ligands 4؊6, the carbazole amine allows catalyst by water proved to be essential. Reaction in the
facile functionalisation. In ongoing studies tailor-made li- absence of water yielded an approximately 1:1 mixture of
gands will be made by variations at the carbazole nitrogen methoxycarbazole (8) and the demethoxylated carbazole 9,
in order to fine-tune the electronics and sterics.
while addition of water shifted this ratio to 99:1 in favour
In this paper a robust synthesis of BICOL, based on the of the desired methoxycarbazole (Scheme 1).
Fischer indole synthesis[ and an oxidative phenol coupling
reaction, is described. The resolution of BICOL is per-
formed by employing both enantiomers of menthyl chloro-
formate as the resolving reagents.
4]
Several oxidative coupling methods were investigated[7] in
order to dimerise hydroxycarbazole 10, obtained from 8 by
cleavage of the methyl ether according to the literature pro-
[5]
cedure. The reaction was carried out successfully using
[8]
either a stoichiometric amount of oxidant [Mn(acac) ] or
3
[
9]
[10]
with the catalysts [CuCl(OH)·TMEDA, VO(acac)2,
Results and Discussion
[11]
CuSO /Al O
] and molecular oxygen as the oxidant. All
4
2
3
reactions yielded the same products in the same ratios;
For the synthesis of 3-hydroxycarbazole 10 we optimised
the route developed by Milne and Tomlinson.[ Tetrahy-
drocarbazole 7, smoothly obtained according to the literat-
4
3
1
0Ϫ50% symmetric bicarbazolediol 1 (BICOL, m.p.
27Ϫ328 °C) and 15Ϫ20% asymmetric dimer 11 (m.p.
97Ϫ199 °C). After completion of the reaction, as was
5]
[
6]
ure procedure from cyclohexanone and 4-methoxyphen-
monitored by TLC, it appeared necessary to remove the
oxidants from the reaction mixture, because extensive stir-
ring under oxygen atmosphere led to over-oxidation of the
diol, yielding probably quinone-like products. Separation of
[
a]
Institute of Molecular Chemistry, University of Amsterdam,
Nieuwe Achtergracht 129, 1018 WS Amsterdam, The
Netherlands
1952
 WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0612Ϫ1952 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2002, 1952Ϫ1955

Synthesis and Resolution of BICOL, a Carbazole Analogue of BINOL
FULL PAPER
diastereomeric mixture of phosphoramidates. Regrettably,
these products proved to be virtually insoluble in the com-
mon solvents, making further purification and/or recrys-
tallisation impossible. More success was obtained with the
[
13a]
procedure developed by De Lucchi et al.,
when we used
menthyl chloroformate 12 as resolving agent (Scheme 2).
Scheme 1
the product from the metal salts and the by-products could
only be accomplished in a practical manner by tedious col-
umn chromatography. The finding that the alumina-sup-
ported copper(II) sulfate catalyst could be easily removed
before column chromatography by filtration made this the
method of choice.
In order to use the carbazole-based diol as chiral ligand,
the resolution of the enantiomers had to be performed. Of
the numerous successful methods for the nonenzymatic res-
olution of BINOL and its derivatives,[
12,13]
several were
tested. Separation by use of N-benzylcinchonidinium chlor-
[12c]
ide (NBC), as described by Reider et al.,
allowed the
formation of inclusion crystals. Unfortunately, these crys-
tals consisted of both enantiomers of BICOL together with
NBC. The next method we considered was the procedure
described by Hu et al.[
13b]
Reacting (Ϯ)-BICOL with
POCl , using a similar procedure as described by Hu et
3
13b]
al.,[
followed by (S)-1-phenylethylamine yielded a 1:1 Scheme 2
Figure 1. ORTEP view of the crystal structure of compound (Ϫ)-14.
Eur. J. Org. Chem. 2002, 1952Ϫ1955
1953

H. Hiemstra et al.
FULL PAPER
Reaction of two equivalents of (Ϫ)-12 and (Ϯ)-BICOL applied for the transfer of air sensitive reagents and dry solvents.
Infrared (IR) spectra were obtained from CHCl
3
solutions, by
in the presence of Et N in acetonitrile gave a 1:1 mixture
3
using a Bruker IFS 28 FT-spectrophotometer and wavelengths ( ν˜ )
of the diastereomers. A single recrystallisation from diiso-
propyl ether yielded colourless crystals of diastereo-
Ϫ1
1
13
are reported in cm
(
.
H and C nuclear magnetic resonance
]acetone with a Bruker
NMR) spectra were determined in [D
6
2
0
merically pure (Ϫ)-14 ([α]D ϭ Ϫ242, m.p. 214 °C) in 67%
yield, based on one diastereomer (Ͼ98% de, checked with
HPLC). After removal of the chiral auxiliary employing
ARX 400 (400 MHz and 100 MHz, respectively) unless indicated
otherwise. Chemical shifts (δ) are given in ppm downfield from
tetramethylsilane. HRMS measurements were carried out using a
JEOL JMS-SX/SX 102 A Tandem Mass Spectrometer. A HP Series
LiAlH as reducing agent, enantiomerically pure (R)-(ϩ)-
4
2
0
BICOL ([α] ϭ ϩ105, m.p. 180Ϫ183 °C) was obtained in 1050 HPLC was used for HPLC experiments, with an Inertsil
a quantitative yield. The residue of the recrystallisation was ODS-S column (l ϫ d ϭ 50 ϫ 4.6 mm, particle size 3µm) with
D
also reduced with LiAlH , yielding an enriched 3:1 mixture acetonitrile/water, 50:50 Ǟ 95:5 (ϩ0.04% formic acid) as the eluent.
4
The detection wavelength was 254 nm. Optical rotations were
measured on a PerkinϪElmer 241 polarimeter in a 1-dm cell
in favour of (S)-(Ϫ)-BICOL. Upon reaction of this mixture
with (ϩ)-menthyl chloroformate (ϩ)-12, a 3:1 mixture of
(
2 mL) in the indicated solvent at the indicated concentration, tem-
the diastereomers was obtained, with (ϩ)-14 in excess. A
single recrystallisation from diisopropyl ether now gave col-
ourless crystals of diastereomerically pure (ϩ)-14 (Ͼ98%
perature and wavelength. Chromatographic purification refers to
flash chromatography[ by using the indicated solvent (mixture)
15]
f
and Acros silica gel (0.035Ϫ0.070 mm). R values were obtained by
using thin-layer chromatography (TLC) on silica gel-coated plastic
sheets (Merck silica gel F254) with PE(60Ϫ80)/EtOAc, 1:1 as the
2
0
de, [α] ϭ ϩ242, m.p. 214Ϫ215 °C) in 82% yield, based on
D
one diastereomer from the 3:1 mixture. In principle, the
mother liquor could be subjected to the same reaction se- eluent unless noted otherwise. Melting points are uncorrected. Dry
quence, using alternatingly (Ϫ)- and (ϩ)-menthyl chloro- THF was distilled from sodium benzophenone ketyl prior to use.
formate. Removal of the chiral auxiliary using LiAlH
Dry acetonitrile was distilled from calcium hydride and stored over
4
yielded enantiomerically pure (S)-(Ϫ)-BICOL ([α]2
0
MS 4 A˚ under a dry argon atmosphere. Triethylamine was dried
ϭ
D
and distilled from KOH pellets. All commercially available reagents
Ϫ105, m.p. 180Ϫ184 °C). The difference in melting point
of ca. 145 °C between racemic and enantiopure BICOL is
remarkable. For BINOL this difference is less than 10 °C.
The crystal structure of (Ϫ)-14 was determined by X-ray
diffraction (Figure 1).[ The absolute configuration could
(
Aldrich or Acros) were used as received, unless indicated other-
wise.
H-Carbazol-3-ol (10): To a solution of 7[6] (5.00 g, 24.8 mmol) in
p-cymene (50 mL) and water (10 mL), 10% Pd on carbon (2.5 g,
9
14]
not be determined unequivocally. However, because the ab- Aldrich) was added. The resulting suspension was refluxed
solute configuration of the starting reagent [(Ϫ)-(1R)-men- (170Ϫ180 °C) for 48 h, cooled to room temperature and filtered.
thyl chloroformate] is known, it is concluded that (Ϫ)-14 The residue was flushed with boiling EtOAc. The collected filtrates
were concentrated in vacuo to yield a 99:1 mixture of 8 and 9
4.80 g, 99%). The crude mixture was used for the synthesis of 10,
contains the (R)-enantiomer of BICOL. The asymmetric
unit contains one molecule of the recrystallisation solvent
diisopropyl ether. The structure shows furthermore that the
two carbazole moieties are positioned almost perpendicular.
The angle between these two planar units is 80.4°.
(
according to the literature procedure. Spectroscopic data were in
accordance with the literature.[
16]
(
؎)-9H,9ЈH-[4,4Ј]Bicarbazole-3,3Ј-diol (BICOL, 1): To a solution
of 8 (3.10 g, 16.9 mmol) in xylene (120 mL) and acetone (22 mL)
was added CuSO /Al (2.3 g). The solution was heated at reflux
4
2 3
O
Conclusions
for 18 h while pure oxygen was bubbled through the suspension.
After cooling to room temperature the dark mixture was filtered
and the solid material on the filter washed with EtOAc. The com-
bined organic fractions were concentrated in vacuo. Purification by
chromatography (PE/EtOAc, 2:1 Ǟ 1:1) yielded 1 (1.53 g, 50%) and
In conclusion, we have described a straightforward syn-
thesis and resolution of BICOL 1. A CuSO /Al O cata-
lysed oxidative phenol coupling allowed the formation of
the bicarbazole skeleton in one step from 3-hydroxycarba-
zole 10. Menthyl chloroformate was successfully used as re-
solving reagent for the resolution of (Ϯ)-BICOL, yielding,
4
2
3
1
3
1 (0.59 g, 19%) as light brown powders. 1: R
27Ϫ328 °C. H NMR: δ ϭ 6.56 (dt, J ϭ 7.2, 0.9 Hz, 2 H), 6.71
f
ϭ 0.24. M.p.
1
(
(
d, J ϭ 8.0 Hz, 2 H), 7.12 (m, 4 H), 7.22 (d, J ϭ 8.6 Hz, 2 H), 7.35
d, J ϭ 8.1 Hz, 2 H), 7.53 (d, J ϭ 8.6 Hz, 2 H), 10.14 (br. s, 2 H)
1
3
after reductive removal of the chiral auxiliary, both enantio- ppm. C NMR ([D ]DMSO): δ ϭ 110.1, 110.3, 114.9, 116.6, 117.2,
6
mers of BICOL in pure form. Studies towards the applica- 121.1, 122.0, 123.0, 124.4, 134.1, 140.4, 147.9 ppm. IR: ν˜ ϭ 3402
ϩ
tion of this new type of BINOL derivatives, by the introduc- (br), 1684. HRMS (FABϩ) calcd. for
24 17 2 2
C H O N (MH )
3
65.1290; found 365.1300.
tion of substituents at the carbazole nitrogens and further
functionalisation of the bicarbazole skeleton (i.e. with phos-
phane or phosphoramidite groups) towards new classes of
ligands will be reported in due course.
1
1
1: R ϭ 0.36. M.p. 197Ϫ199 °C. H NMR: δ ϭ 6.87 (t, J ϭ 7.2,
Hz, 1 H), 7.06 (t, J ϭ 7.2 Hz, 1 H), 7.12 (dd, J ϭ 8.8, 2.5 Hz, 1
H), 7.21 (m, 2 H), 7.32 (m, 2 H), 7.43 (m, 3 H), 7.60 (d, J ϭ 2.5 Hz,
f
1
1
H), 7.81 (m, 2 H), 7.90 (d, J ϭ 7.8 Hz, 1 H), 10.17 (br. s, 1 H),
0.23 (br. s, 1 H) ppm. C NMR: δ ϭ 104.7, 107.8, 110.7, 111.0,
1
3
Experimental Section
111.5, 114.1, 116.7, 117.2, 118.0, 118.1, 120.2, 120.7, 122.1, 122.2,
22.8, 125.2, 125.6, 135.0, 135.1, 135.8, 140.2, 140.5, 142.6, 151.5
ppm. IR: ν˜ ϭ 3406 (br), 1691. HRMS (FABϩ) calcd. for
1
All reactions were carried out under an inert atmosphere of dry
argon, unless stated otherwise. Standard syringe techniques were
ϩ
C
24
H
17
O
2
N
2
(MH ) 365.1290; found 365.1292.
1954
Eur. J. Org. Chem. 2002, 1952Ϫ1955

Synthesis and Resolution of BICOL, a Carbazole Analogue of BINOL
FULL PAPER
Resolution of BICOL: To a stirred solution of racemic BICOL 1
Acknowledgments
(
1.00 g, 2.75 mmol) and Et
27 mL) was added dropwise (Ϫ)-(1R)-menthyl chloroformate (Ϫ)-
2 (1.36 mL, 6.30 mmol). The solution was stirred at room temper-
ature for 1 h. The reaction was quenched by addition of EtOAc
100 mL) and water (100 mL). The layers were separated and the
aqueous layer was extracted with EtOAc (2 ϫ 50 mL). The com-
bined organic layers were dried over Na SO and concentrated in
3
N (1.91 mL, 13.7 mmol) in acetonitrile
These investigations are financially supported by the National Re-
search School Combination Catalysis (NRSCC). A. van Loevezijn
and M. Koch are kindly acknowledged for their assistance with the
HPLC measurements. H. I. V. Amatdjais-Groenen (University of
Nijmegen) is kindly acknowledged for the elemental analysis meas-
urements.
(
1
(
2
4
vacuo. Purification by chromatography (PE/EtOAc, 5:1Ǟ2:1) af-
forded a 1:1 diastereomeric mixture as an off-white solid (1.71 g,
[
[
1]
2]
M. McCarthy, P. J. Guiry, Tetrahedron 2001, 57, 3809Ϫ3844.
[2a]
For recent reviews see:
C. Rosini, L. Franzini, A. Raffaelli,
f
85%). R ϭ 0.50 (for both diastereomers). The mixture was dis-
[
2b]
P. Salvadori, Synthesis 1991, 503.
H. B. Kagan, O. Riant,
solved in refluxing diisopropyl ether (8 mL) and set aside at room
temperature overnight. The resulting crystals were collected,
washed with diisopropyl ether and dried in vacuo, yielding (Ϫ)-14,
as a single diastereomer (0.57 g, 67% yield based on one diastere-
[2c]
Chem. Rev. 1992, 92, 1007.
K. Mikami, M. Shimizu, Chem.
L. Pu, Chem. Rev. 1998, 2405.
Noyori, Asymmetric Catalysis in Organic Synthesis; Wiley: New
York, 1994. G. Bringmann, R. Walter, R. Weirich, Angew.
Rev. 1992, 1021. [
2d]
[2e]
R.
[2f]
omer). [α]2
0
0
0
ϭ Ϫ242 (c ϭ 1.0, CHCl
.24 (d, J ϭ 6.9 Hz, 6 H), 0.62 (d, J ϭ 7.0 Hz, 6 H), 0.67 (m, 4 H),
.79 (d, J ϭ 6.5 Hz, 6 H), 0.85 (m, 2 H), 1.04 (m, 2 H), 1.27 (m, 4
). M.p. 214 °C. H NMR: δ ϭ
1
D
3
Chem. Int. Ed. Engl. 1990, 29, 997.
[
[
3] [3a]
A. E. Sollewijn Gelke, J. Fraanje, K. Goubitz, H. Schenk,
H. Hiemstra, Tetrahedron 1997, 53, 5899. [ A. E. Sollewijn
3b]
H), 1.49 (m, 4 H), 1.75 (m, 2 H), 4.14 (dt, J ϭ 4.4, 10.9 Hz, 2 H),
Gelpke, H. Kooijman, A. L. Spek, H. Hiemstra, Chem. Eur. J.
1
999, 5, 2472.
6
8
.57 (m, 4 H), 7.13 (dt, J ϭ 6.5, 1.7 Hz, 2 H), 7.42 (dd, J ϭ 8.7,
4] [4a]
[4b]
1
3
E. Fischer, F. Jourdan, Ber. 1883, 16, 2241.
E. Fischer,
O. Hess, Ber. 1884, 17, 559. [ E. Dreschsel, J. Prakt. Chem.
888, 38, 69.
.2 Hz, 4 H), 7.72 (d, J ϭ 8.7 Hz, 2 H), 10.57 (s, 2 H) ppm.
C
4c]
NMR: δ ϭ 16.3, 20.9, 22.4, 24.1, 26.8, 32.1, 34.9, 41.1, 47.8, 79.1,
1
1
1
7
11.6, 111.9, 119.4, 121.2, 123.0, 123.2, 123.3, 124.0, 126.5, 139.1,
42.1, 143.2, 154.3. HRMS (FABϩ) calcd. for C46H N O (MH )
53 2 6
29.3904, found 729.3950.
[5]
[6]
[7]
A. H. Milne, M. L. Tomlinson, J. Chem. Soc. 1952, 2789.
C. U. Rogers, B. B. Corson, J. Am. Chem. Soc. 1947, 69, 2910.
For recent literature about oxidative biaryl coupling reactions
see: X. Li, J. Yang, M. C. Kozlowski, Org. Lett. 2001, 3, 1137
and references herein.
ϩ
The remaining filtrate was concentrated in vacuo, yielding a yellow
solid (1.13 g, 1.55 mmol). After dissolving the mixture in anhyd-
rous THF (31 mL), LiAlH (0.58 g, 10.9 mmol) was added in 3
4
portions over 10 min. The reaction mixture was stirred for 1 h at
room temperature. The reaction was carefully quenched by adding
water, EtOAc and 1  aqueous HCl. The layers were separated and
the aqueous phase was extracted with EtOAc (3 ϫ 60 mL). The
combined organic layers were dried over Na SO and concentrated
2 4
in vacuo. Purification by chromatography (PE/EtOAc, 1:1) afforded
a 3:1 mixture of (S)-BICOL and (R)-BICOL as a white solid
[8]
M. J. S. Dewar, T. Nakaya, J. Am. Chem. Soc. 1968, 90, 7134.
M. Nakajima, I. Miyoshi, K. Kanayama, S. Hashimoto, J. Org.
Chem. 1999, 64, 2264.
[
9]
[
[
[
10]
11]
12]
D.-R. Hwang, C.-P. Chen, B.-J. Uang, Chem. Commun. 1999,
1
207.
T. Sakamoto, J. Yonehara, C. Pac, J. Org. Chem. 1994, 59,
859.
For recent literature describing the resolution of BINOL and
6
[12a]
its derivatives using cinchonidinium derivatives, see:
K.
Tanaka, T. Okada, F. Toda, Angew. Chem. Int. Ed. Engl. 1993,
(0.41 g, 100% yield).
[12b]
3
2, 1147.
F. Toda, K. Tanaka, Z. Stein, I. Goldberg, J.
[12c]
Org. Chem. 1994, 59, 5748.
D. Cai, D. L. Hughes, T. R.
The 3:1 mixture was reacted with (ϩ)-menthyl chloroformate (ϩ)-
2 according to the procedure described above, yielding a 3:1 mix-
[12d]
Verhoeven, P. J. Reider, Tetrahedron Lett. 1995, 36, 7991.
F. Toda, K. Tanaka, Chem. Commun. 1997, 1087. [
12e]
Q.-S.
1
ture of diastereomers (1.08 g, 96%). After recrystallisation from di-
isopropyl ether (5 mL) the formed cubic crystals were collected,
washed with diisopropyl ether and dried in vacuo, yielding (ϩ)-14,
Hu, D. Vitharana, L. Pu, Tetrahedron: Asymm. 1995, 6, 2123.
[12f]
Y. Wang, J. Sun, K. Ding, Tetrahedron 2000, 56, 4447.
[13]
For recent literature describing the resolution of BINOL and
[
13a]
its derivatives using covalently bound chiral auxiliaries, see:
as a single diastereomer (0.66 g, 82% yield calculated from the 3:1
mixture). [α]2
0
D. Fabbri, G. Delogu, O. De Lucchi, J. Org. Chem. 1995, 60,
D
ϭ ϩ242 (c ϭ 1.0, CHCl
3
ϩ
). M.p. 214Ϫ215 °C. HRMS
599. [
991, 56, 423.
13b]
6
1
B. Q. Gong, W. Y. Chen, B. F. Hu, J. Org. Chem.
(FABϩ) calcd. for C46
H
53
N
2
O
6
(MH ) 729.3904, found 729.3889.
[13c]
D. Fabbri, G. Delogu, O. De Lucchi, J. Org.
Spectroscopic data are identical to (Ϫ)-14.
[13d]
Chem. 1993, 58, 1748.
Z. Shan, Y. Xiong, D. Zhao, Tetra-
hedron 1999, 55, 3893. [
13e]
H. C. Kim, S. Choi, H. Kim, K.-
Both diastereomerically pure (Ϫ)-14 and (ϩ)-14 were treated with
[13f]
H. Ahn, Tetrahedron Lett. 1997, 38, 3959.
Buono, J. Org. Chem. 1993, 58, 7313.
J. M. Brunel, G.
LiAlH
4
according to the procedure described above, yielding en-
[13g]
M. Periasamy, A. S.
antiomerically pure (R)-(ϩ)-BICOL and (S)-(Ϫ)-BICOL, respect-
Bhanu Prasad, J. V. Bhaskar Kanth, C. Kishan Reddy, Tetra-
hedron: Asymm. 1995, 6, 341.
ively, in a quantitative yield after purification by chromatography
ϭ 0.24. [α]2
0
ϭ ϩ105 (c ϭ
[14]
[15]
(EtOAc/PE ϭ 1:1). (R)-(ϩ)-BICOL; R
f
D
CCDC-176699 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
1
.0, THF). M.p. 180Ϫ183 °C. HRMS (FABϩ) calcd. for
ϩ
C
24
H
17
N
2
O
2
(MH ) 365.1290, found 365.1296. C24
EtOAc: calcd. C 75.95, H 5.03, N 6.70; found C 76.02, H 4.92, N
.41. Spectroscopic data are identical to (Ϯ)-BICOL and confirmed
the presence of EtOAc.
16 2 2
H N O ·0.6
6
W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923.
Spectroscopic data 8: H.-J. Knölker, M. Bauermeister, J.-B.
Pannek, Chem. Ber. 1992, 125, 2783. Spectroscopic data 10:
H.-J. Knölker, M. Bauermeister, J.-B. Pannek, M. Wolpert,
Synthesis 1995, 397.
[16]
(
1
3
S)-(Ϫ)-BICOL: R
f
ϭ 0.24. [α]20
80Ϫ184 °C. HRMS (FABϩ) calcd. for C24
65.1290, found 365.1284. C24 ·0.8 EtOAc: calcd. C 75.15,
D
ϭ Ϫ105 (c ϭ 1.0, THF). M.p.
ϩ
17 2 2
H N O (MH )
16 2 2
H N O
H 5.19, N 6.45; found C 75.13, H 4.89, N 6.31. Spectroscopic data
Received January 11, 2002
are identical to (Ϯ)-BICOL and confirmed the presence of EtOAc.
[O02014]
Eur. J. Org. Chem. 2002, 1952Ϫ1955
1955