Enantioselective Friedel-Crafts type addition of indoles to nitro-olefins using a chiral hydrogen-bonding catalyst - Synthesis of optically active tetrahydro-β-carbolines

Article abstract of DOI:10.1039/b505220c

The enantioselective Friedel-Crafts addition of indoles to nitro-olefins using chiral hydrogen-bonding bis-sulfonamides as the catalysts has been developed. The reactions, in the presence of only 2 mol% catalyst, generally proceed in high yields and with

Full text of DOI:10.1039/b505220c

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A R T I C L E
Enantioselective Friedel–Crafts type addition of indoles to
nitro-olefins using a chiral hydrogen-bonding catalyst – synthesis of
optically active tetrahydro-b-carbolines
Wei Zhuang, Rita G. Hazell and Karl Anker Jørgensen*
Danish National Research Foundation: Center for Catalysis, Department of Chemistry, Aarhus
University, DK-8000 Aarhus C, Denmark. E-mail: kaj@chem.au.dk; Fax: 45 8619 6199;
Tel: 45 8942 3910
Received 14th April 2005, Accepted 26th May 2005
First published as an Advance Article on the web 21st June 2005
The enantioselective Friedel–Crafts addition of indoles to nitro-olefins using chiral hydrogen-bonding
bis-sulfonamides as the catalysts has been developed. The reactions, in the presence of only 2 mol% catalyst, generally
proceed in high yields and with enantioselectivities up to 64% ee, and the enantiomeric excess can be improved to
>98% ee by recrystallization. Various synthetic transformations of the Friedel–Crafts adducts are demonstrated: the
nitro group can easily be reduced to the corresponding amine and the product obtained can undergo a
stereocontrolled Pictet–Spengler cyclization to give, for example, enantiopure tetrahydro-b-carbolines. The X-ray
structure of the chiral bis-sulfonamides has been determined and based on these structures the mechanism for the
stereoselectivity in the reaction is discussed.
Introduction
Results and discussion
The addition of heteroaromatic compounds to nitro-olefins, the
Friedel–Crafts type Michael reaction, is an important reaction
in organic chemistry because valuable synthetic building blocks
are obtained by this aromatic electrophilic substitution.1,2 These
reactions are normally performed in a non-enantioselective
fashion using Lewis acid-3 or organo-catalysis.4
The reaction of b-nitrostyrene 1a with N-methyl indole 2a
was studied for different chiral hydrogen bond catalysts under
various reaction conditions [eqn. (2)].13
Recently, it has been shown that hydrogen-bonding interac-
tions play a crucial role in some organocatalytic enantioselec-
tive reactions.5 However, hydrogen-bonding-catalyzed Friedel–
Crafts type alkylation to nitro-olefins is still an unexplored field
compared with the enantioselective Michael addition to nitro-
olefins catalyzed, for example, by L-proline and its derivatives,6
chiral urea7 and cinchona alkaloids.8
Vicinal diamine derivatives attract extensive investigation in
asymmetric synthesis due to their important role as a chiral
ligand in Lewis acid complexes.9 Chiral bis-sulfonamide cata-
lysts are easily prepared from chiral diamines10 and potentially
activate the oxygen atoms of the nitro-olefin via a hydrogen-
bonding interaction with the acidic hydrogen atoms. This
paper presents the catalytic, enantioselective Friedel–Crafts type
reaction of nitrostyrenes 1 to heteroaromatic compounds 2
catalyzed by chiral vicinal diamine derivatives – bis-sulfonamide
(4) – as the chiral hydrogen bond donors [eqn. (1)].
Some representative examples for the reaction catalyzed by the
bis-sulfonamides 4 are presented in Table 1.
The results in Table 1 show that without catalyst no reaction
was observed between b-nitrostyrene 1a and N-methyl indole
2a (Table 1, entry 1). Using only 2 mol% of 4a as the catalyst,
the desired Friedel–Crafts product 3a was obtained with high
conversion and up to 26% ee at room temperature (entry 2).
Replacement of catalyst 4a with 4b–d led to a clear decrease
in both conversion and enantioselectivity of the Friedel–Crafts
reaction (entries 3–5), whereas the use of the less acidic hydrogen
bond catalyst 4e did not yield the desired product (entry 6).
A number of other solvents were also successfully applied to
the catalytic enantioselective Friedel–Crafts reaction (entries
7–10). Decreasing the reaction temperature to −24 ◦C led to
an increase of the enantioselectivity of product 3a to 43% ee
(entry 11). Lowering the temperature further to −40 ◦C did not
improve the enantioselectivity; however, lower conversion was
found (entry 12). Application of a catalyst loading of 1 and
0.5 mol% did not affect the enantioselectivity of the reaction,
but longer reaction times were required to maintain the high
conversion (entries 13, 14).
The Friedel–Crafts products (3) formed by this reaction are
potential starting materials for many biologically active com-
pounds, e.g. physostigmine,11 that is isolated from seeds of
Physostigma venenosum (Calabar beans) and serves as a clini-
cally useful anticholinergic drug.12
2 5 6 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 6 6 – 2 5 7 1
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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Table 1 Result for the enantioselective Friedel–Crafts reaction of b-nitrosytrene 1a with N-methyl indole 2a catalyzed by bis-sulfonamides 4 under
various reaction conditions
Entry
Catalyst
Solvent
T/◦C
Time/h
Conversion (%)a
Ee (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13c
14d
—
4a
4b
4c
4d
4e
4a
4a
4a
4a
4a
4a
4a
4a
CH2Cl2
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
CH2Cl2
ClCH2CH2Cl
THF
Toluene
CH2Cl2
CH2Cl2
Toluene
CHCl3
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
−24
−40
−24
−24
16
18
40
40
40
16
18
18
18
18
40
40
60
96
0
100
64
65
72
0
100
98
35
95
85
65
90
83
—
26
4
0
4
—
21
26
18
27
43
43
46
47
a Determined by 1H NMR. b Determined on crude samples by chiral stationary HPLC. c 1 mol% catalyst. d 0.5 mol% catalyst.
The 1,2-diphenyltrifluoromethanesulfonamide 4a catalyzed
Friedel–Crafts reaction [eqn. (3)] proceeded well for various
nitro-olefins 1 and the results are presented in Table 2.
The results for the reaction of b-nitrostyrene 1a with the
indoles 2b–f catalyzed by 2 mol% 4a in CHCl3 [eqn. (4)]
are shown in Table 3. It appears from the results in Table 3
that changing from N-methyl-protected indole (2a) to the
unprotected indole (2b), the high yield was maintained, but the
enantioselectivity was eroded (entry 1). Other indoles with a
more bulky protecting group on the nitrogen atom were also
applied in the Friedel–Crafts reaction; however, neither the
yield nor the enantiomeric excess of the corresponding product
was improved (entries 2, 3). However, N-methyl-5-methoxy-
indole 2e reacted with 1a to give 3l in high yield (87%) and
good enantioselectivity (64% ee) (entry 4). According to entry
5 (Table 3) the chloro-substituted indole 2f does furnish the
product 3m in only 27% yield.
First, it is worthy to note that the reaction also proceeded
well in the presence of 50 mg silica gel as a mild heterogeneous
catalyst and that the corresponding product was isolated in 97%
yield (Table 1, entry 1).15 In toluene, nitrostyrene 1a reacted with
N-methyl indole 2a to give 91% yield and up to 50% ee (entry 2).
The reaction proceeded with good yield and moderate enantios-
electivity for nitrostyrene having electron-withdrawing groups
(1b,c) (entries 3, 4). However, introduction of electron-rich
substituents on the phenyl group in the nitrostyrene 1d resulted
in lower enantioselectivity (entry 5). When the b-substituent was
heteroaryl, moderate enantiomeric excess of the corresponding
product was observed (entries 6, 7), whereas alkyl-substituents
at the b-position of the nitro-olefin dramatically decreased the
enantioselectivity of the reaction (entries 8, 9).
The Friedel–Crafts adducts obtained can be recrystallized
in Et2O/hexane giving these compounds as optically pure, as
shown for 3a. Furthermore, the nitro group in, for example, 3a
can easily be reduced by Pd/C in the presence of NH4CO2H,
followed by reaction with methyl chloroformate to the corre-
sponding amide 6 in high yield and without significant loss of
enantiomeric excess (Scheme 1).
Another important synthetically useful aspect of the reaction
is that the corresponding optically enriched Friedel–Crafts
adduct can be applied in substrate-controlled Pictet–Spengler
Table 2 Results for the catalytic, enantioselective Friedel–Crafts re-
action of b-nitro-olefins 1 with N-methyl indole 2a in the presence of
2 mol% 4a as the catalyst
T/◦C
Yielda (%) Eeb,c (%)
Table 3 Results for the catalytic enantioselective Friedel–Crafts reac-
tion of b-nitro-olefins 1a with methyl indole 2 in the presence of 2 mol%
4a as the catalyst
Entry Substrate Solvent
1d
2
3
4
5
6
7
8
9
1a
1a
1b
1c
1d
1e
1f
CHCl3
Toluene
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
Toluene
Toluene
rt
97 (3a)
91 (3a)
62 (3b)
53 (3c)
66 (3d)
63 (3e)
77 (3f)
56 (3g)
84 (3h)
—
50
−24
−24
−24
−24
−24
−24
−24
−24
Entry
Substrate
T/◦C
Yielda (%)
Eeb,c (%)
45 (51)
40 (46)
32 (33)
40 (40)
43 (45)
11 (23)
19 (20)
1
2
3
4
5
2b
2c
2d
2e
2f
−24
−24
−24
−40
−24
86 (3i)
20 (3j)
37 (3k)
87 (3l)
27 (3m)
15 (11)
36 (35)
13 (26)
63 (64)
40 (43)
1g
1h
a Isolated yield. b Ee of the isolated product determined by chiral
stationary HPLC. c The ee value in parentheses is the enantiomeric excess
before column chromatography.14 d Silica gel 50 mg.
a Isolated yield. b Ee of the isolated product determined by chiral
stationary HPLC. c The ee value in parentheses is the enantiomeric excess
before column chromatography.14
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 6 6 – 2 5 7 1
2 5 6 7

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Fig. 1 X-Ray structure of the bis-sulfonamide catalyst 4a.
intermediate.18 Unfortunately, these crystallization experiments
gave separate crystallization of 4a and 1a.
Scheme 1 Reduction of the nitro functionality and proection of the
We have used the structure of the bis-sulfonamide catalyst
4a in an attempt to understand the enantioinduction in the
reaction. By the coordination of nitrostyrene as proposed in
Fig. 2, the Re-face of the alkene is shielded by the phenyl-
substituents in the chiral catalyst, leaving the Si-face available
for approach of the indole. Owing to the relatively large N–C–
C–N dihedral angle in catalyst 4a (64.2◦), the amino hydrogen
atoms are enantiotopic, whereas for catalyst 4b, in which the
dihedral angle N–C–C–N is only 19.4◦, the amino hydrogen
atoms are probably ‘less enantiotopic’ compared to catalyst 4a.
For the interaction of nitrostyrene with catalyst 4b, the smaller
N–C–C–N dihedral angle could then lead to an intermediate
in which the substituents at the chiral carbon atoms shield the
Re-face of the substrate to a lesser extent compared with the bis-
sulfonamide catalyst having a large N–C–C–N dihedral angle.
amino functionality.
cyclization16 to form tetrahydro-b-carboline and tetrahydroiso-
quinoline ring systems, which are key building blocks for
natural and synthetic compounds possessing important bio-
logical activities.17 By reduction of 3a (99% ee) with Pd/C
and NH4CO2H, followed by treatment with benzaldehyde and
TFA, it was found that the original chirality in 3a controlled
the stereochemistry of the newly formed stereogenic center
in the acid-catalyzed Pictet–Spengler reaction to give 7 as
major diastereoisomer (dr = 5 : 1). Finally, N-Boc protection,
or reaction with p-chlorobenzoyl chloride, gave 8a or 8b,
respectively, of which the absolute configuration of the latter has
been characterized by X-ray analysis (Scheme 2). On the basis
of the absolute configuration of the compound obtained in the
reaction of 7 with p-chlorobenzoyl chloride the stereochemical
outcome was assigned to be (S).
Fig. 2 Proposed interaction of nitrostyrene with one of the amino
hydrogen atoms in bis-sulfonamide catalyst 4a (the hydrogen atoms in
the catalyst are omitted, with the exception of those at the chiral carbon
atoms and the nitrogen atoms).
Conclusion
We have shown that chiral hydrogen-bonding bis-sulfonamides
are effective catalysts for the enantioselective Friedel–Crafts
addition of indoles to nitro-olefins. The reactions proceed with
only 2 mol% of the catalyst and the optically active Friedel–
Crafts adducts are obtained in high yields and with enantios-
electivities up to 64% ee, and the enantiomeric excess can be
improved to >98% ee by recrystallization. The scope of the
development is demonstrated by reduction of the nitro group to
the amine and the stereocontrolled Pictet–Spengler cyclization
to give enantiopure tetrahydro-b-carbolines. Furthermore, we
have, based on the X-ray structure of the chiral bis-sulfonamides,
proposed an intermediate for the reaction.
Scheme 2 Synthetic transformations of optically active 3a.
In an attempt to try to understand the induction of enantios-
electivity in the reaction, we have obtained the X-ray structures
of the bis-sulfonamide catalysts 4a–d. The structure of 4a, which
gives the highest enantioselectivity, is shown in Fig. 1.
Experimental
An interesting change in structure of the bis-sulfonamide
catalysts 4a–d, which might be related to the enantioselectivity
introduced by the catalysts, is found when comparing the
dihedral angle N–C–C–N. This dihedral angle in 4a is found
to be 64.2◦, whereas the same dihedral angle in 4b is only 19.4◦.
The use of 4a as the catalyst can give up to 64% ee, whereas 4b
provides a nearly racemic product. Furthermore, we have also
tried to crystallize a 1 : 1 mixture of the bis-sulfonamide catalyst
4a and nitrostyrene 1a under various conditions in order to try
to obtain structural information about the catalyst–substrate
General methods
The 1H NMR and 13C NMR spectra were recorded at 400 and
100 MHz, respectively. The chemical shifts are reported in ppm
relative to CHCl3 (d 7.26) for 1H and relative to the central CDCl3
resonance (d 77.0) for 13C NMR. Flash chromatography (FC)
was carriedout using Merck silicagel 60(230–400 mesh). Optical
rotation was measured on a Perkin-Elmer 241 polarimeter. All
1
diastereoselectivities were measured by H NMR spectroscopy
2 5 6 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 6 6 – 2 5 7 1

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on crude reaction mixtures. The enantiomeric excess (ee) of
the products was determined by chiral HPLC using Daicel
Chiralpak or Daicel Chiralcel columns with hexane–2-propanol
as eluent, as indicated in the respective entries.
C,C,C - Trifluoro - N - (2 - trifluoromethanesulonylaminocyclo -
hexyl)methanesufonamide (4d). [a]rDt = +1.7 (c = 1.0 g per
100 mL, MeOH); 1H NMR (CDCl3) d 5.01 (s, 2H), 3.25 (s, 2H),
2.30 (d, J = 13.2 Hz, 2H), 1.84 (d, J = 7.6 Hz, 2H), 1.44–1.31
(m, 4H); 13C NMR (CDCl3) d 59.3, 34.2, 24.7. C8H12F6N2O4S2,
M = 397.43, crystallizes in the trigonal space group P3221
Materials
with unit cell dimensions: a = b = 14.3841(2), c = 13.9800(4)
b-Nitrosytrene 1a and its derivatives 1b–f, N-methyl indole 2a,
and indole 2b were purchasedcommercially andusedas received.
Bis-sulfonamide catalysts10 4a–e, N-protected indoles19 2c–f,
alkyl-substituted nitrostyrenes20 1g,h were prepared according
to literature procedures.
3
˚
˚
A, V = 2504.97(9) A at T = 100 K, Z = 6, l(MoKa) =
0.398 mm−1. A total of 24 180 reflections were measured,
averaging to 6270 independent, Rint = 0.081; 5312 reflections
with I > 2rI were used in the refinements finishing at R =
0.034, Rw = 0.036. The structure contains large channels along
the unique axis filled by solvent molecules (n-hexane). The
solvent is completely disordered forming an infinite chain. The
absolute configuration was established by refinement according
to Rogers21 using all 5312 significant reflections including 2288
Bijvoet pairs.
N-(1,2-Diphenyl-2-trifluoromethanesulfonylaminoethyl)-C,C,C-
trifluoromethanesulfonamide (4a). [a]rDt = +5.2 (c = 1.0 g
per 100 mL, CHCl3); 1H NMR (CDCl3) d 7.21–7.18 (m,
6H), 6.92–6.90 (m, 4H), 4.71 (s, 2H); 13C NMR (CDCl3) d
135.1, 129.2, 129.0, 127.0, 63.7. C16H14F6N2O4S2, M = 476.42,
crystallizes in the hexagonal space group P6522 with unit
CCDC reference number 270613. See http://www.rsc.org/
suppdata/ob/b5/b505220c/ for crystallographic data in CIF
or other electronic format.
˚
cell dimensions: a = b = 11.6353(10), c = 52.806(9) A, V =
3
−1
˚
6191.1(13) A at T = 100 K, Z = 12, l(MoKa) = 0.336 mm .
A total of 62 518 reflections were measured, averaging to 5037
independent, Rint = 0.107; 4303 reflections with I > 3rI were
used in the refinements finishing at R = 0.064, Rw = 0.081. The
absolute configuration was established by refinement according
to Rogers21 using all 4303 significant reflections including 1598
Bijvoet pairs.
General procedure for the enantioselective Friedel–Crafts type
addition to nitro-olefins
To a stirred solution of the nitro-olefin (0.625 mmol) and
hydrogen-bonding catalyst (2 mol%) in the solvent (0.5 mL),
indole (1.25 mmol) was added and stirred at ambient tempera-
ture for 60 h. The reaction mixture was purified by FC on silica
gel (Et2O–pentane) to give the corresponding Friedel–Crafts
adduct.
CCDC reference number 272816. See http://www.rsc.org/
suppdata/ob/b5/b505220c/ for crystallographic data in CIF
or other electronic format.
N -(1-tert-Butyl-3,3-dimethyl-2-trifluoromethanesulfonyl-
aminobutyl)-C,C,C-trifluoromethanesulfonamide (4b). [a]Drt
=
1-Methyl-3-(2-nitro-1-phenylethyl)-1H-indole (3a). The ee
was determined by HPLC using a Daicel Chiralcel AS column
1
+31.6 (c = 0.7 g per 100 mL, MeOH); H NMR (CDCl3) d
4.60 (s, br, 2H), 3.72 (d, J = 8.0 Hz, 2H), 1.04 (s, 18H); 13C
NMR (CDCl3) d 61.2, 36.1, 26.6. C12H22F6N2O4S2, M = 436.46,
crystallizes in the tetragonal space group P4122 with unit
(hexane–2-propanol = 97 : 3, flow rate 1.0 mL min−1, sminor
=
15.1 min; smajor = 17.4 min). [a]rDt = +3.1 (c = 1.4 g per 100 mL,
CHCl3, 50% ee); 1H NMR (CDCl3) d 7.47 (d, J = 7.6 Hz, 1H),
7.38–7.23 (m, 7H), 7.10 (m, 1H), 6.88 (s, 1H), 5.21 (t, J = 8.0 Hz,
1H), 5.06 (dd, J = 12.4, 8.0 Hz, 1H), 4.95 (dd, J = 12.4, 8.0 Hz,
1H), 3.75 (s, 3H); 13C NMR (CDCl3) d 139.3, 137.2, 128.8 (2C),
127.7 (2C), 127.5, 126.5, 126.3, 122.2, 119.4, 118.9, 112.7, 109.5,
79.5, 41.5, 32.8.
˚
cell dimensions: a = b = 12.2564(3), c = 13.4713(6) A, V =
3
−1
˚
2023.65(11) A at T = 100 K, Z = 4, l(MoKa) = 0.335 mm .
A total of 61 260 reflections were measured, averaging to 4269
independent, Rint = 0.954; 3636 reflections with I > 3rI were
used in the refinements finishing at R = 0.044, Rw = 0.093. The
absolute configuration was established by refinement according
to Rogers21 using all 3636 significant reflections including 1466
Bijvoet pairs.
3-[1-(4-Bromophenyl)-2-nitroethyl]-1-methyl-1H-indole (3b).
The ee was determined by HPLC using a Daicel Chiralcel AS
column (hexane–2-propanol = 80 : 20, flow rate 1.0 mL min−1,
sminor = 18.6 min; smajor = 22.5 min). [a]rDt = −1.9 (c = 1.4 g
per 100 mL, CHCl3, 45% ee); 1H NMR (CDCl3) d 7.45 (m, 1H),
7.34–7.22 (m, 6H), 7.12 (m, 1H), 6.87 (s, 1H), 5.16 (t, J = 8.0 Hz,
1H), 5.03 (dd, J = 12.4, 8.0 Hz, 1H), 4.90 (dd, J = 12.4, 8.0 Hz,
1H), 3.75 (s, 3H); 13C NMR (CDCl3) d 138.4, 137.2, 131.9 (2C),
129.4 (2C), 126.2 (2C), 122.2, 121.3, 119.5, 118.7, 112.0, 109.6,
79.1, 40.9, 32.8.
CCDC reference number 270611. See http://www.rsc.org/
suppdata/ob/b5/b505220c/ for crystallographic data in CIF
or other electronic format.
N -(1,2-Dicyclohexyl-2-trifluoromethanesulfonylaminoethyl)-
C,C,C-trifluoromethanesulfonamide (4c). 1H NMR (CDCl3)
d 3.39 (s, 2H), 1.84–1.42 (m, 22H); 13C NMR (CDCl3) d 61.1,
40.1, 31.3, 27.1, 26.1, 26.0, 25.9. C16H26F6N2O4S2, M = 488.53,
crystallizes in a layer structure with much disorder, twinning as
well as diffuse streaks. The strong spots from one crystal were
indexed on a monoclinic unit cell, space group C2/c with unit
1-Methyl-3-[2-nitro-1-(2-nitrophenyl)ethyl]-1H-indole
(3c).
The ee was determined by HPLC using a Daicel Chiralcel AD
column (hexane–2-propanol = 90 : 10, flow rate 1.0 mL min−1,
sminor = 34.8 min; smajor = 37.8 min). [a]rDt = +74.6 (c = 1.0 g
per 100 mL, CHCl3, 40% ee); 1H NMR (CDCl3) d 7.86 (d, J =
8.4 Hz, 1H), 7.48–7.17 (m, 6H), 7.00 (m, 1H), 6.97 (s, 1H),
5.84 (t, J = 8.0 Hz, 1H), 5.04 (m, 2H), 3.71 (s, 3H); 13C NMR
(CDCl3) d 149.5, 137.2, 133.9, 133.2, 129.8, 128.5, 126.6, 126.3,
125.0, 122.4, 119.7, 118.7, 111.0, 109.5, 78.1, 36.3, 32.9. HRMS
C17H15N3O4 [M + Na]+ calculated 348.0960; found 348.0963.
˚
cell dimensions: a = 20.6214(6), b = 10.7987(7), c = 9.401(3) A,
3
−1
˚
V = 2082.1(7) A at T = 100 K, Z = 4, l(MoKa) = 0.335 mm .
A total of 33 027 reflections were measured, averaging to 4126
independent, Rint = 0.109; 2968 reflections with I > 2rI were
used in the refinements finishing at R = 0.143, Rw = 0.169.
The structure within one layer (and thereby of the molecule) is
believed to be correct, but the stacking of layers varies within
the crystal and from crystal to crystal. Another crystal had its
strong reflections indexed on a triclinic cell with a = 9.432(2),
3-[1-(4-Methoxyphenyl)-2-nitroethyl]-1-methyl-1H-indole (3d).
The ee was determined by HPLC using a Daicel Chiralcel AS
column (hexane–2-propanol = 95 : 5, flow rate 1.0 mL min−1,
sminor = 26.1 min; smajor = 31.2 min). [a]rDt = +2.4 (c = 2.0 g
˚
b = 10.891(3), c = 11.339(3) A, a = 104.54, b = 109.09(2), c =
90.05(2)◦. The disorder-streaks had fewer well defined maxima.
It solved in space group P1 to give the same structure within
the layer but a different stacking of layers.
1
per 100 mL, CHCl3, 32% ee); H NMR (CDCl3) d 7.44 (d,
CCDC reference number 270612. See http://www.rsc.org/
suppdata/ob/b5/b505220c/ for crystallographic data in CIF
or other electronic format.
J = 8.4 Hz, 1H), 7.31–7.21 (m, 4H), 7.07 (t, J = 7.2 Hz, 1H),
6.87–6.85 (m, 3H), 5.13 (t, J = 8.0 Hz, 1H), 5.04 (dd, J = 12.4,
7.6 Hz, 1H), 4.89 (dd, J = 12.0, 8.4 Hz, 1H), 3.78 (s, 3H), 3.75
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 6 6 – 2 5 7 1
2 5 6 9

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(s, 3H); 13C NMR (CDCl3) d 158.8, 147.3, 131.3, 128.8 (2C),
126.5, 126.2, 122.2, 119.4, 119.0, 114.2 (2C), 113.1, 109.5, 79.7,
55.2, 40.8, 32.8.
7.35–7.20 (m, 7H), 7.09 (td, J = 7.2, 1.2 Hz, 1H), 6.93 (s, 1H),
6.03–5.93 (m, 1H), 5.23–5.18 (m, 2H), 5.17–5.04 (m, 2H), 4.95
(dd, J = 12.4, 8.8 Hz, 1H), 4.70–4.68 (m, 2H); 13C NMR (CDCl3)
d 139.2, 136.7, 133.1, 128.9 (2C), 127.7 (2C), 127.5, 126.7, 125.2,
122.2, 119.6, 119.1, 117.5, 113.1, 109.9, 79.5, 48.8, 41.5. HRMS
C19H18N2O2 [M + Na]+ calculated 329.1266; found 329.1265.
3-(1-Furan-2-yl-2-nitroethyl)-1-methyl-1H-indole (3e). The
ee was determined by HPLC using a Daicel Chiralcel AS column
(hexane–2-propanol = 95 : 5, flow rate 1.0 mL min−1, smajor
=
34.2 min; sminor = 38.6 min). [a]rDt = −16.8 (c = 2.0 g per 100 mL,
CHCl3, 40% ee); 1H NMR (CDCl3) d 7.51 (d, J = 8.4 Hz, 1H),
7.34 (d, J = 1.6 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.21 (td,
J = 7.6, 1.2 Hz, 1H), 7.09 (td, J = 7.6, 0.8 Hz, 1H), 6.94 (s,
1H), 6.27 (dd, J = 3.2, 2.0 Hz, 1H), 6.13 (d, J = 3.2 Hz, 1H),
5.19 (t, J = 8.0 Hz, 1H), 5.00 (dd, J = 12.4, 8.4 Hz, 1H), 4.86
(dd, J = 12.8, 7.2 Hz, 1H), 3.71 (s, 3H); 13C NMR (CDCl3)
d 152.3, 142.2, 137.1, 127.3, 126.1, 122.1, 119.5, 118.8, 110.4,
109.9, 109.6, 107.2, 77.9, 35.6, 32.8. HRMS C15H14N2O3 [M +
Na]+ calculated 293.0902; found 293.0915.
1-Benzyl-3-(2-nitro-1-phenylethyl)-1H-indole (3k). The ee
was determined by HPLC using a Daicel Chiralcel AS column
(hexane–2-propanol = 95 : 5, flow rate 1.0 mL min−1, sminor
=
15.1 min; smajor = 17.7 min). [a]rDt = +4.9 (c = 1.9 g per 100 mL,
CHCl3, 13% ee); 1H NMR (CDCl3) d 7.47 (d, J = 7.6 Hz, 1H),
7.37–7.25 (m, 10H), 7.18 (t, J = 8.0 Hz, 1H), 7.08 (t, J = 7.2 Hz,
2H), 6.99 (s, 1H), 5.29 (s, 2H), 5.22 (t, J = 8.0 Hz, 1H), 5.07
(dd, J = 12.4, 7.6 Hz, 1H), 4.95 (dd, J = 12.4, 8.4 Hz, 1H);
13C NMR (CDCl3) d 139.2, 137.1, 136.8, 128.8 (2C), 128.7 (2C),
127.7 (2C), 127.6, 127.5, 126.7, 126.6 (2C), 125.6, 122.4, 119.6,
119.1, 113.4, 110.0, 79.5, 50.0, 41.5. HRMS C23H20N2O2 [M +
Na]+ calculated 379.1422; found 379.1427.
1-Methyl-3-(2-nitro-1-thiophen-2-ylethyl)-1H-indole
(3f).
The ee was determined by HPLC using a Daicel Chiralcel AS
column (hexane–2-propanol = 95 : 5, flow rate 1.0 mL min−1,
smajor = 43.5 min; sminor = 51.2 min). [a]rDt = +5.2 (c = 1.8 g per
5-Methoxy-1-methyl-3-(2-nitro-1-phenylethyl)-1H-indole (3l).
The ee was determined by HPLC using a Daicel Chiralcel AS
column (hexane–2-propanol = 99 : 1, flow rate 1.0 mL min−1,
sminor = 63.7 min; smajor = 68.8 min). [a]rDt = −12.3 (c = 1.7 g per
1
100 mL, CHCl3, 43% ee); H NMR (CDCl3) d 7.51 (d, J =
7.6 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.24 (t, J = 8.0 Hz, 1H),
7.19 (dd, J = 4.8, 1.2 Hz, 1H), 7.10 (td, J = 4.0, 1.2 Hz, 1H),
6.99–6.93 (m, 3H), 5.44 (t, J = 8.0 Hz, 1H), 5.05–4.94 (m, 2H),
3.76 (s, 3H); 13C NMR (CDCl3) d 143.1, 139.2, 126.9, 126.6,
126.1, 125.1, 124.8, 122.3, 119.6, 118.9, 112.4, 109.6, 80.1, 36.9,
32.9. HRMS C15H14N2O2S [M + Na]+ calculated 309.0674;
found 309.0684.
1
100 mL, CHCl3, 63% ee); H NMR (CDCl3) d 7.36–7.28 (m,
5H), 7.20 (d, J = 8.8 Hz, 1H), 6.93–6.89 (m, 2H), 6.85 (s, 1H),
5.16 (t, J = 8.0 Hz, 1H), 5.04 (dd, J = 12.4, 8.0 Hz, 1H), 4.93
(dd, J = 12.4, 8.0 Hz, 1H), 3.80 (s, 3H), 3.70 (s, 3H); 13C NMR
(CDCl3) d 153.9, 139.3, 132.6, 128.9 (2C), 127.7 (2C), 127.5,
126.8 (2C), 112.2, 112.1, 110.3, 100.8, 79.4, 55.8, 41.4, 33.0.
3-(1-Cyclohexyl-2-nitroethyl)-1-methyl-1H-indole (3g). The
6-Chloro-1-methyl-3-(2-nitro-1-phenylethyl)-1H-indole (3m).
The ee was determined by HPLC using a Daicel Chiralcel AS
column (hexane–2-propanol = 99 : 1, flow rate 1.0 mL min−1,
sminor = 77.6 min; smajor = 82.8 min). [a]rDt = +2.5 (c = 1.0 g per
ee was determined by HPLC using a Daicel Chiralcel AS column
(hexane–2-propanol = 99 : 1, flow rate 1.0 mL min−1, smajor
=
32.6 min; sminor = 37.4 min). [a]rDt = −4.5 (c = 1.4 g per 100 mL,
CHCl3, 11% ee); 1H NMR (CDCl3) d 7.61 (d, J = 7.6 Hz, 1H),
7.31 (d, J = 7.6 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 7.14 (t, J =
7.6 Hz, 1H), 6.86 (s, 1H), 4.81 (dd, J = 8.0, 6.4 Hz, 1H), 4.72
(dd, J = 12.0, 9.6 Hz, 1H), 3.75 (s, 3H), 3.69 (m, 1H), 1.87–
1.63 (m, 6H), 1.32–0.99 (m, 5H); 13C NMR (CDCl3) d 136.9,
127.3, 126.8, 121.7, 119.1, 119.0, 111.5, 109.4, 78.5, 41.7, 40.4,
32.7, 31.4, 30.3, 26.2, 26.1, 26.1. HRMS C17H22N2O2 [M + Na]+
calculated 309.1579; found 309.1585.
1
100 mL, CHCl3, 40% ee); H NMR (CDCl3) d 7.35–7.26 (m,
7H), 7.02 (dd, J = 8.4, 1.2 Hz, 1H), 6.89 (s, 1H), 5.14 (t, J =
8.0 Hz, 1H), 5.01 (dd, J = 12.4, 8.0 Hz, 1H), 4.91 (dd, J = 12.4,
8.0 Hz, 1H), 3.71 (s, 3H); 13C NMR (CDCl3) d 139.0, 137.6,
129.0 (2C), 128.2, 127.6 (2C), 126.8, 125.1, 120.1, 119.9 (2C),
113.0, 109.5, 79.4, 41.3, 32.9.
2 - ( 1 - Methyl - 1H - indol - 3 - yl ) - 2 - phenylethylamine ( 5a ).
0.39 mmol of optically pure 3a was dissolved in 10 mL MeOH
then 148 mg NH4CO2H and 70 mg Pd/C was added and the
mixture was stirred for 6 h at 60 ◦C. After filtered Pd/C, MeOH
was removed in vacuo and 5a was obtained without further
1-Methyl-3-(1-nitromethylhexyl)-1H-indole (3h). The ee was
determined by HPLC using a Daicel Chiralcel AS column
(hexane–2-propanol = 99 : 1, flow rate 1.0 mL min−1, smajor
=
17.6 min; sminor = 19.8 min). [a]rDt = −5.0 (c = 1.5 g per 100 mL,
CHCl3, 19% ee); 1H NMR (CDCl3) d 7.53 (d, J = 8.0 Hz, 1H),
7.22 (d, J = 8.0 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.04 (t,
J = 7.6 Hz, 1H), 6.80 (s, 1H), 4.59–4.49 (m, 2H), 3.72–3.62
(m, 1H), 3.65 (s, 3H), 1.80–1.63 (m, 2H), 1.18 (m, 5H), 0.78–
0.73 (m, 4H); 13C NMR (CDCl3) d 136.9, 137.2, 126.5, 121.8,
119.1, 118.8, 112.4, 109.5, 80.7, 36.2, 32.7, 32.4, 31.6, 26.8, 22.4,
14.0. HRMS C17H22N2O2 [M + Na]+ calculated 297.1579; found
297.1583.
1
purification. H NMR (CDCl3) d 7.39 (d, J = 8.0 Hz, 1H),
7.27–7.10 (m, 7H), 7.10 (t, J = 7.6 Hz, 1H), 6.82 (s, 1H), 4.17
(t, J = 7.2 Hz, 1H), 3.68 (s, 3H), 3.34 (dd, J = 12.4, 7.2 Hz,
1H), 3.20 (dd, J = 12.4, 7.6 Hz, 1H), 1.50 (s, br, 2H); 13C NMR
(CDCl3) d 143.1, 137.2, 128.5, 128.1, 127.4, 126.3, 126.0, 121.7,
119.4, 118.8, 116.1, 109.2, 47.4, 46.9, 32.7. HRMS C17H18N2
[M + H]+ calculated 251.1548; found 251.1537.
[2-(1-Methyl-1H-indol-3-yl)-2-phenylethyl]carbamic acid methyl
ester (6). Compound 5a was dissolved in a mixture of CH2Cl2
and saturated Na2CO3 solution (1 : 1, 10 mL) and 1.17 mmol
methyl chlorofomate was added. The reaction mixture was
stirred at room temperature for 24 h and extracted by CH2Cl2,
dried by Na2SO4. The solvent was removed in vacuo. The residue
was purified by FC (20% Et2O–petane) to obtain 6 in 92% yield
based on 3a. The ee of 6 was determined by HPLC using a
Daicel Chiralcel AS column (hexane–2-propanol = 97 : 3, flow
+11.0 (c = 1.0 g per 100 mL, CHCl3, 96% ee); 1H NMR (CDCl3)
d 7.51 (d, J = 8.0 Hz, 1H), 7.35–7.21 (m, 7H), 7.06 (t, J = 8.0 Hz,
1H), 6.88 (s, 1H), 4.78 (s br, 1H), 4.44 (t, J = 8.0 Hz, 1H), 4.00
(m, 1H), 3.80–3.70 (m, 1H), 3.76 (s, 3H), 3.65 (s, 3H); 13C NMR
(CDCl3) d 156.9, 142.1, 137.2, 128.6 (2C), 128.0 (2C), 127.2,
126.7, 126.3, 121.8, 119.5, 119.0, 115.1, 109.2, 52.0, 45.7, 43.1,
3-(2-Nitro-1-phenylethyl)-1H-indole (3i). The ee was deter-
mined by HPLC using a Daicel Chiralcel AD column (hexane–
2-propanol = 90 : 10, flow rate 1.0 mL min−1, sminor = 23.4 min;
smajor = 25.4 min). [a]Drt = +0.8 (c = 2.0 g per 100 mL, CHCl3,
11% ee); 1H NMR (CDCl3) d 8.05 (s br, 1H), 7.41 (d, J = 8.0 Hz,
1H), 7.32–7.14 (m, 7H), 7.04 (td, J = 7.6, 1.2 Hz, 1H), 6.97 (d,
J = 2.4 Hz, 1H), 5.15 (t, J = 8.0 Hz, 1H), 5.04 (dd, J = 12.4,
8.0 Hz, 1H), 4.90 (dd, J = 12.4, 8.0 Hz, 1H); 13C NMR (CDCl3)
d 139.1, 136.4, 129.0, 128.9, 127.7, 127.5, 127.0, 126.1, 122.7,
121.6, 119.9, 118.9, 114.4, 111.4, 79.5, 41.5.
rate 1.0 mL min−1, sminor = 27.4 min; smajor = 32.0 min). [a]rDt
=
1-Allyl-3-(2-nitro-1-phenylethyl)-1H-indole (3j). The ee was
determined by HPLC using a Daicel Chiralcel AD column
(hexane–2-propanol = 95 : 5, flow rate 1.0 mL min−1, sminor
=
9.3 min; smajor = 11.8 min). [a]rDt = +7.8 (c = 0.9 g per 100 mL,
CHCl3, 36% ee); 1H NMR (CDCl3) d 7.46 (d, J = 8.4 Hz, 1H),
2 5 7 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 6 6 – 2 5 7 1

View Article Online
32.7. HRMS C19H20N2O2 [M + Na]+ calculated 331.1422; found
References and notes
1 For a review of asymmetric Michael addition to nitroalkenes, see:
O. M. Berner, L. Tedeschi and D. Enders, Eur. J. Org. Chem., 2002,
1877.
2 For a review of asymmetric Friedel–Crafts alkylation, see: M.
Bandini, M. Melloni and A. Umani-Ronchi, Angew. Chem., Int. Ed.,
2004, 43, 550.
3 See, for example: K. Lee and D. Y. Oh, Tetrahedron Lett., 1988, 29,
2977; T. Ohe and S. Uemura, Tetrahedron Lett., 2002, 43, 1269; K.
Manabe, N. Naoyama and S. Kobayashi, Adv. Synth. Catal., 2001,
343, 174; J. S. Yadav, S. Abraham, B. V. S. Reddy and G. Sabitha,
Synthesis, 2001, 2165; M. Bandini, P. Melchiorre, A. Melloni and A.
Umani-Ronchi, Synthesis, 2002, 1110; H. Firouzabadi, N. Iranpour
and N. Nowrouzi, Chem. Commun., 2005, 789.
4 See, for example: M. Bandini, M. Fagioli and A. Umani-Ronchi,
Adv. Synth. Catal., 2004, 346, 545; G. Dessole, R. P. Herrera and A.
Ricci, Synlett, 2004, 2374.
5 For reviews, see, for example: P. M. Pihko, Angew. Chem., Int.
Ed., 2004, 43, 2062; P. R. Schreiner, Chem. Soc. Rev., 2003, 32,
289; P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed., 2004, 43,
5138.
6 J. M. Betancort and C. F. Barbas, III, Org. Lett., 2001, 3, 3737; A.
Alexakis and O. Andrey, Org. Lett., 2002, 4, 3611; J. M. Betancort,
K. Sakthivel, R. Thayumanavan and C. F. Barbas, III, Tetrahedron
Lett., 2001, 42, 4441; A. J. A. Cobb, D. A. Longbottom, D. M. Shaw
and S. V. Ley, Chem. Commun., 2004, 1808; B. List, P. Pojarliev and
H. Martin, Org. Lett., 2001, 3, 2423; D. Enders and A. Seki, Synlett,
2002, 26; W. Wang, J. Wang and H. Li, Angew. Chem., Int. Ed., 2005,
44, 1369.
7 T. Okino, Y. Hoashi and Y. Takemoto, J. Am. Chem. Soc., 2003, 125,
12 672; Y. Hoashi, T. Yabuta and Y. Takemoto, Tetrahedron Lett.,
2004, 45, 9185.
8 H. Li, Y. Wang, L. Tang and L. Deng, J. Am. Chem. Soc., 2004, 126,
9906; H. Li, Y. Wang, L. Tang, F. Wu, X. Liu, C. Guo, B. M. Foxman
and L. Deng, Angew. Chem., Int. Ed., 2005, 44, 105.
9 For a review, see, for example: D. Lucet, T. L. Gall and C.
Mioskowski, Angew. Chem., Int. Ed., 1998, 37, 2581.
10 Synthesis of chiral diamines, see, for example: E. J. Corey, R.
Imwinkelried, S. Pikul and Y. B. Xiang, J. Am. Chem. Soc., 1989, 111,
5493; E. J. Corey, D.-H. Lee and S. Sarshar, Tetrahedron: Asymmetry,
1995, 6, 3; S. Roland and P. Mangeney, Eur. J. Org. Chem, 2000, 611;
S. Rolan and P. Mangeney, Synthesis, 1999, 228.
11 For review of Calabar alkaloids, see, for example: S. Takano and K.
Ogasawara, Alkaloids, 1989, 36, 225; B. Robinson, Alkaloids, 1971,
13, 213.
12 For reviews of pharmacology, see: N. H. Greig, X. F. Pei, T. T.
Soncrant, D. K. Ingram and A. Brossi, Med. Res. Rev., 1995, 15,
3.
13 Other catalysts were also tested for the reaction of 1a with 2a. For
example, 10 mol% (R)-BINOL at room temperature in CH2Cl2 gave
no conversion.
14 The slightly lower enantiomeric excess after column chromatography
is due to fact that some of the Friedel–Crafts reactions never proceed
to completion and the remaining starting materials react during the
chromatography procedure catalyzed by silica gel to give a racemic
product, thereby lowering the enantiomeric excess.
15 Silica gel-catalyzed reaction, see, for example: H. Kotsuki, K.
Hayashida, T. Shimanouchi and H. Nishizawa, J. Org. Chem., 1996,
61, 984.
331.1418.
9-Methyl-1,4-diphenyl-1,3,4,9-tetrahydro-b-carboline-2-
carboxylic acid tert-butyl ester (8a). .59 mmol of optically
pure 3a was dissolved in 10 mL MeOH then 224 mg NH4CO2H
and 80 mg Pd/C was added and the mixture was stirred for 6 h
at 60 ◦C. After filtered Pd/C, MeOH was removed in vacuo.
The residue was dissolved in 10 mL CH2Cl2 and 0.59 mmol
benzaldehyde was added together with 0.5 g MgSO4. The
reaction mixture was stirred at room temperature for 24 h
and the suspension was filtered and the solvent was removed
in vacuo. The residue was dissolved in 10 mL CH2Cl2 and
cooled to 0 ◦C and then 1.18 mmol TFA was added slowly.
The reaction mixture was then warmed to room temperature.
After being stirred for 40 h, saturated NaHCO3 was added
and the mixture was extracted with EtOAc. The combined
organic phase was washed by brine, dried with MgSO4 and
concentrated. Most of the impurities were removed by FC
(10% Et2O–CH2Cl2) to obtain 7 followed by the addition of
220 mg di-tert-butyldicarbonate in 5 mL MeOH. The solution
was stirred at room temperature overnight and purified by FC
(5% Et2O–CH2Cl2). The ee of 8a was determined by HPLC
using a Daicel Chiralcel OD column (hexane–2-propanol = 99
: 1, flow rate 1.0 mL min−1, sminor = 7.0 min; smajor = 9.3 min).
[a]rDt = +139.5 (c = 1.3 g per 100 mL, CHCl3, 99% ee); 1H NMR
(CDCl3) d 7.33–7.09 (m, 13H), 7.02 (t, J = 8.0 Hz, 1H), 6.76 (s,
1H), 4.33 (d, J = 4.0 Hz, 1H), 4.13 (d, J = 13.6 Hz, 1H), 3.46
(dd, J = 13.6, 4.0 Hz, 1H), 3.43 (s, 3H), 1.06 (s, 9H); 13C NMR
(CDCl3) d 154.7, 143.4, 139.7, 137.5, 134.4, 128.6 (2C), 128.4
(2C), 128.1 (2C), 128.0, 128.0 (2C), 126.1, 126.0, 121.6, 119.2,
118.8, 110.9, 108.9, 79.6, 52.4, 45.6, 38.8, 30.0, 27.8 (3C). HRMS
C29H30N2O2 [M + Na]+ calculated 461.2205; found 461.2211.
(4-Chlorophenyl)-(9-methyl-1,4-diphenyl-1,3,4,9-tetrahydro-
b-carbolin-2-yl)methanone (8b). The procedure above was
followed to form compound 7 (0.14 mmol) which was dissolved
in CH2Cl2 with the addition of p-chlorobenzoyl chloride
(0.14 mmol) and pyridine (0.14 mmol). The reaction mixture
was stirred at room temperature overnight and concentrated.
The crude product was purified by FC and crystallized in
Et2O–hexane. 1H NMR (CDCl3) d 7.36–7.34 (m, 7H), 7.26–7.21
(m, 5H), 7.05–6.94 (m, 5H), 6.33 (d, J = 8.0 Hz, 2H), 4.34 (d,
J = 3.6 Hz, 1H), 3.76 (dd, J = 13.2, 4.8 Hz, 1H), 3.62 (d, J =
14.0, 4.0 Hz, 1H), 3.50 (s, 3H); 13C NMR (CDCl3) d 170.2,
142.0, 139.1, 137.8, 134.6, 134.0, 133.6, 128.9 (2C), 128.6 (4C),
128.5, 128.3 (2C), 128.1 (2C), 127.7 (2C), 126.8, 125.7, 121.9,
119.5, 118.9, 110.0, 109.1, 51.0, 48.7, 39.0, 30.1. C31H25Cl1N2O1,
M = 397.43, crystallizes in the trigonal space group P31 with
˚
the unit cell dimensions: a = b = 10.0175(8) A, c = 21.2378(13)
◦
◦
3
˚
˚
A, a = b = 90 , c = 120 , V = 1845.7(2) A at T = 225 K,
Z = 3, l = 0.182 mm−1. A total of 10 444 reflections were
measured, reduced to 4167 unique reflections after merging
with SORTAV22a with an Rint = 0.049. The refinement of 316
parameters against all data resulted in an Rw(F2) of 0.09 and
a goodness of fit of 0.96. The absolute configuration was
established by anomalous dispersion methods and the Flack
parameter22b refined to be 0.03(6).
16 E. D. Cox and J. M. Cook, Chem. Rev., 1995, 95, 1797; M. S. Taylor
and E. N. Jacobsen, J. Am. Chem. Soc., 2004, 126, 10 588 and refs.
cited therein.
17 K. W. Bentley, Nat. Prod. Rep., 2004, 21, 395 and refs. cited therein.
18 For a recent structure of a benzaldehyde–chiral biaryl diol complex,
see: A. K. Unni, N. Takenaka, H. Yamamoto and V. H. Rawal, J. Am.
Chem. Soc., 2005, 127, 1336.
19 C. A. Merlic, Y. You, D. M. McInnes, A. L. Zechman, M. M.
Miller and Q. Deng, Terahedron, 2001, 57, 5199; P. J. Beswick, C. S.
Greenwood, T. J. Mowlem, G. Nechvatal and D. A. Widdowson,
Terahedron, 1988, 44, 7235.
20 S. E. Denmark and L. Marcin, J. Org. Chem., 1995, 60, 3221; S. E.
Denmark and L. Marcin, J. Org. Chem., 1993, 58, 3580.
21 D. Rogers, Acta Crystallogr., Sect. A, 1981, 37, 734.
22 (a) R. H. Blessing, J. Appl. Crystallogr., 1989, 22, 396; (b) H. D.
Flack, Acta Crystallogr., Sect. A, 1983, 39, 876.
CCDC reference number 268882. See http://www.rsc.org/
suppdata/ob/b5/b505220c/ for crystallographic data in CIF
or other electronic format.
Acknowledgements
This work was made possible by a grant from The Danish
National Research Foundation. Thanks are expressed to Dr
Jacob Overgaard for X-ray analysis of 8b.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 5 6 6 – 2 5 7 1
2 5 7 1