Achiral and-amino acid derived dicationic imidazoliophanes

Article abstract of DOI:10.1055/s-0030-1258183

Achiral and chiral imidazoliophanes were prepared by N-alkylation of chiral imidazole derivatives featuring an-amino acid motif and subsequent double quarternization of the imidazole N3-position of the corresponding precyclophanes. Eight new optically pure imidazoliophanes were synthesized in good yields, whereas the molecular structure of one achiral analogue was confirmed by X-ray analysis. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258183

3188
PAPER
Achiral and a-Amino Acid Derived Dicationic Imidazoliophanes
D
icationic Imidaz
o
l
liophan
e
e
s
š Marek,a Jiří Kulhánek,a W. B. Schweizer,b Filip Bureš*a
a
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice
532 10, Czech Republic
Fax +420(46)6037068; E-mail: filip.bures@upce.cz
Laboratorium für Organische Chemie, ETH-Zürich, Hönggerberg, HCI, Zürich 8093, Switzerland
b
Received 12 April 2010; revised 2 June 2010
tically active precursors for further syntheses, which
prompted us to report herein the synthesis of achiral and
a-amino acid derived N-(di)substituted imidazoles 4/5
and 6 as well as imidazoliophanes 7–10.
Abstract: Achiral and chiral imidazoliophanes were prepared by
N-alkylation of chiral imidazole derivatives featuring an a-amino
acid motif and subsequent double quarternization of the imidazole
N3-position of the corresponding precyclophanes. Eight new opti-
cally pure imidazoliophanes were synthesized in good yields,
whereas the molecular structure of one achiral analogue was con-
firmed by X-ray analysis.
R1 = α-amino acid residue
R1
N
R1
R1
N
NHCbz
NHCbz
NHCbz
Key words: cyclophanes, imidazoliophanes, amino acids, chiral
pool, ligands
O
N
N
X
N
N
R2
1
1
,2
N
R2 = H (
) or CH2OEt (2)
a
b
c
d
R1 = Me [(S)-Ala]
R1 = s-Pr [(S)-Val]
R1 = i-Bu [(S)-iLe]
R1 = Bn [(S)-Phe]
Annular a-amino-derived macrocycles steadily attract
considerable attention of organic chemists due to their
biological, catalytic and binding activities.1 Furthermore,
their structures represent tempting synthetic challenges.
Among others, heterocyclic compounds incorporating an
imidazole nucleus and diverse imidazole-based systems
are investigated for their unique properties such as acid-
base character, imidazole tautomerism, hydrogen bond-
ing, coordination properties, or aromaticity.2 Thus, imida-
zole-containing compounds have found wide applications
as ionic liquids,3 biologically active substances,4 nitrogen
ligands,5 carbenes,6 or p-conjugated scaffolds.7 However,
the most widely known naturally occurring imidazole de-
rivative is certainly the essential a-amino acid – histidine.
In general terms, application of the a-amino acids as enan-
tiopure synthetic precursors for such systems seems to be
advantageous because of their readily availability and low
cost.8 Thus, combination of the imidazole nucleus with an
a-amino acid residue brings into the molecule chiral infor-
mation and such optically active molecules have found
application in asymmetric synthesis and chiral recogni-
tion.
4
,
5
3
X = N, O, C
2 Br–
2 Br–
Y
Y
Y
R1
R1
R1
CbzHN
R1
NHCbz
N
N
N
N
N
N
R1
R1
N
N
R2 R2
6
7–9 and 10
R1 = H, Ph or α-amino acid residue
R2 = CH2OEt
= CH, N
Y
Figure 1 Recently synthesized a-amino acid-derived imidazoles
1–3 and newly proposed 1-substituted imidazoles 4/5 and 1,3-disub-
stituted imidazoles 6, 7–9, and 10
Whereas the imidazole derivatives 1–3 and 4/5 are un-
charged, 1,3-disubstituted (bridged) imidazoles 6 and
7–10 are dicationic. Although a variety of chiral cyclo-
phanes with different structures and properties have
already been reported,11 imidazoliophanes featuring
a-amino acid residues similar to 10 are quite rare.12 How-
ever, (benz)imidazoliophanes have found wide applica-
tion as model structures for anion recognition,13 as
antibacterially active substances,14 and in particular, for
N-heterocyclic carbenes with unique metal coordination
abilities.15
Inspired by the molecule of histidine, we have recently re-
ported the synthesis of optically active a-amino acid de-
rivatives 1 (Figure 1).9 The synthesis of 1 started from the
corresponding a-amino acids, their stepwise transforma-
tion into the a-bromo ketones, and subsequent condensa-
tion with formamidine to afford target imidazoles 1. More
recently, we have used the Cbz-protected amines 2 as
starting compounds for the construction of ligands 3 via
Negishi and Suzuki–Miyaura cross-coupling reactions
(Figure 1).10 Thus, the amines 1/2 proved to be useful op-
The first attempted synthesis of imidazoles 4/5 started
from imidazole 1b derived from (S)-valine and 2-(bro-
momethyl)pyridine as an alkylating agent (Scheme 1). As
expected, the reaction carried out in an acetonitrile/NaOH
system16 afforded two regioisomers 4b and 5b in a ratio of
3:1 and 74% overall yield. This is in contrast to our previ-
ous observations,10 resulting in the ethoxymethylation of
imidazoles 1 affording 1:1 mixture of both regioisomers
SYNTHESIS 2010, No. 18, pp 3188–3194
x
x.
x
x
.
2
0
1
0
Advanced online publication: 16.07.2010
DOI: 10.1055/s-0030-1258183; Art ID: Z09010SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Dicationic Imidazoliophanes
Table 1 Pincer type ligands 6
3189
NHCbz
Product Starting
imidazole
R
Y
Reaction time Yield
(days)
(%)
NHCbz
+
HN
NHCbz
Br
N
N
6a
6c
6d
2a
2c
2d
Me/(S)-Ala
i-Bu/(S)-Leu
Bn/(S)-Phe
CH
N
6
7
7
67
1b
NaOH, MeCN, 25 °C
N
N
N
N
51
N
N
N
59
4b
5b
Scheme 1 The first attempted synthesis of N-substituted imidazole
4/5
With verified N-alkylation and subsequent quarterniza-
tion of imidazoles 1 and 2 in this way, the synthesis of pre-
cyclophanes 11, 12, 14, 15, and imidazoliophanes 7–10
was conducted. The synthesis of precyclophanes 11, 12,
14, and 15 started from chiral 4(5)-substituted imidazoles
1a–d or the commercially available 4,5-diphenylimida-
zole (13). The N-alkylation of these imidazoles with
either 1,3-bis(bromomethyl)benzene or 2,6-bis(bromo-
methyl)pyridine in a similar ways as for 4/5 afforded the
desired precyclophanes in 61–92% yields. Since the start-
ing chiral 4(5)-substituted imidazoles 1a–d exhibit 1H-
imidazole tautomerism, three different regioisomeric
products are possible. However, the formation of only two
of the three possible regioisomers was observed. The less
sterically hindered regioisomers 11a–e with 1,4-disubsti-
tuted imidazoles were isolated as the major products. A
mixture of both regioisomers 11 (1,4-disubstituted) and
12 (1,4- and 1,5-disubstituted) could be separated by two
consecutive column separations. Similar to 4b/5b, the re-
gioisomers 11/12 were isolated in approximate ratios of
3:1 (a–c) and 2:1 (d,e). It should be noted that the N-alkyl-
ation using THF instead of MeCN afforded generally low-
er yields (e.g., 43% conversion for 11a/12a). Only the
symmetric chiral precyclophanes 11a–d along with
achiral 14 and 15 were further used for the construction of
2. However, both regioisomers 4b/5b could be separated
by two consecutive chromatographic separations.
Delighted with such smooth reaction course, the second
alkylation of imidazole was attempted at the N3 position.
Thus, the quarternization of imidazoles 2 with either 1,3-
bis(bromomethyl)benzene or 2,6-bis(bromomethyl)pyri-
dine, carried out in acetone at reflux,15f afforded three 1,3-
disubstituted dicationic imidazoles 6 in 51–67% yields
(Scheme 2, Table 1).
R
NHCbz
2 Br–
Br
Br
O
Y
N
N
CbzHN
R
NHCbz
R
Y
N
N
2a,c,d
acetone, reflux
N
N
Y = CH, N
O
O
6a,c,d
Scheme 2 Synthesis of 1,3-disubstituted imidazoles 6
R
R
R
CbzHN
NHCbz
+
NHCbz
R
N
N
N
N
N
NHCbz
R
N
N
N
N
Br
Br
HN
CbzHN
Y
Y
Y
1a–d
NaOH, MeCN, 25 °C
Y = CH, N
11a–e
12a–e
Ph
Ph
HN
N
Br
Br
Ph
Ph
Ph
Y
13
N
N
NaOH, MeCN, 25 °C
Ph
N
N
Y = CH, N
Y
Br
Br
14 Y = CH
15 Y = N
Y
2 Br–
Ph
2 Br–
R
R
Y
Y
Y
Y
Y = CH, N
acetone, reflux
14, 15 and 11a–e
Ph
Ph
N
N
N
N
N
N
CbzHN
NHCbz
N
N
Ph
7–9
10a–e
Scheme 3 The synthesis of precyclophanes 11,12/14,15 and imidazoliophanes 7–9/10
Synthesis 2010, No. 18, 3188–3194 © Thieme Stuttgart · New York

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A. Marek et al.
PAPER
Table 2 Precyclophanes 11,12/14,15 and Imidazoliophanes 7–9/10
Product
11a/12a
11b/12b
11c/12c
11d/12d
11e/12e
14
Starting material R
Y
Time (h)
16
Conversion (%) Yields of 11/12 (%)
1a
Me/(S)-Ala
N
83a
86a
73a
93a
94a
65
58/19b
1b
i-Pr/(S)-Val
i-Bu/(S)-Leu
Bn/(S)-Phe
Me/(S)-Ala
–
N
20
62/22b
1c
N
20
52/16b
1d
N
20
55/32b
1e
CH
CH
N
72
61/31b
13
20
–
–
–
–
–
–
–
–
–
–
15
13
–
20
61
7
14
–
CH/CH
CH/N
N/N
N/N
N/N
N/N
N/N
CH/CH
192
120
48
95
8
14
–
84
9
15
–
88
10a
11a
11b
11c
11d
11e
Me/(S)-Ala
i-Pr/(S)-Val
i-Bu/(S)-Leu
Bn/(S)-Phe
Me/(S)-Ala
96
92
10b
192
96
82
10c
85
10d
144
168
98
10e
76
a Isolated mixture of regioisomers 11 and 12 (after first column chromatography).
b Isolated yields for pure regioisomers 11/12 (after second column chromatography).
the target imidazoliophanes. The quarternization reaction, the adjacent CH and CH2 groups (see Supporting Informa-
carried out in anhydrous acetone at reflux (4–8 days), af- tion). The prepared compounds also provided satisfactory
forded the target imidazoliophanes 7–9 and 10 as pure elemental analyses and ESI-MS spectra. In addition, slow
white precipitates in 76–98% yields (Scheme 3, Table 2).
evaporation of a methanol solution of cyclophane 9 at
20 °C afforded crystals suitable for X-ray analysis. The
ORTEP plots in Figure 2 confirmed the molecular struc-
ture and spatial arrangement of 9. There are two symmetry
independent molecules with Ci site symmetry. They show
the same conformation with the exception of the phenyl
The assigned molecular structures of all the synthesized
compounds were confirmed by 1H and 13C NMR spectros-
copy employing 1H-1H COSY, 1H-13C HMQC, and
HMBC methods. The 2D NMR analyses showed, in par-
ticular, interactions between the imidazole C4 and C5 and
Figure 2 ORTEP drawing showing one of the two symmetry independent molecules in the crystal structure of 9 (left: upper view, right: side
view) at 223 K. Ellipsoids are shown at 50% probability level. Solvent molecules (MeOH) and anions (Br–) were omitted for clarity.
Synthesis 2010, No. 18, 3188–3194 © Thieme Stuttgart · New York

PAPER
Dicationic Imidazoliophanes
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mL). The combined organic layers were dried (Na2SO4) and the sol-
vent evaporated. The crude product was purified by two consecu-
tive column chromatographic separations. The first separation (Rf1)
afforded a pure mixture of both regioisomers that were separated on
a second column (Rf2).
ring at C5, which differ by 40° in the torsion angle of the
two ring planes. In general, imidazoliophanes in solution
have been observed previously to exhibit interconversion
between syn and anti conformations of the bridged imida-
zole moiety.17 Although the measured 1H NMR spectra of
our cyclophanes showed an averaged signal for all the
CH2 groups adjacent to the imidazole, the crystal structure
revealed the presence of only the anti conformation with
the reversed parallel imidazole units and nearly vertically
oriented bridging pyridine moieties.
2,6-Bis{[4-(1-(1S)-benzyloxycarbonylaminoethyl)-1H-imidazol-
1-yl]methyl}pyridine (11a)
The title compound was synthesized from 1a and 2,6-bis(bromom-
ethyl)pyridine following the general procedure; yield: 172 mg
(58%); yellowish oil; Rf1 = 0.40 (silica gel; hexane–EtOAc–
MeOH–NH4OH, 3:5:1:0.1); Rf2 = 0.36 (silica gel; acetone–
MeOH, 10:1), [a]D22 –13.6 (c 0.5, MeOH).
In conclusion, the N-alkylation and subsequent quar-
ternization of either achiral or a-amino acid-derived imi-
dazoles have been reported. Following such synthetically
1H NMR (500 MHz, CDCl3): d = 1.45 (6 H, d, J = 6.7 Hz, 2 ×
CH3CH), 4.81–4.84 (2 H, m, 2 × CHNH), 5.00–5.08 (8 H, m, 2 ×
simple methodology, pincer type ligands 6 and 11,12/ CH2Ph and 2 × CH2Py), 5.80–5.86 (2 H, m, 2 × CHNH), 6.75 (2 H,
2 s, 2 × 5-Him), 6.88 (2 H, d, J = 6.6 Hz, Py), 7.23–7.31 (10 H, m,
Ar), 7.44 (2 H, s, 2 × 2-Him), 7.58 (2 H, t, J = 7.7 Hz, Py).
14,15 (precyclophanes) as well as imidazoliophanes 7–9
and 10 were constructed. Overall, eight new optically pure
imidazoliophanes were synthesized in good yields and the
molecular structure of 9 was also confirmed by X-ray
analysis.
13C NMR (125 MHz, CDCl3): d = 21.6 (2 × CH3CH), 45.2 (2 × CH),
52.2 (2 × PyCH2), 66.5 (2 × PhCH2), 115.5 and 115.5 (2 × 5-Cim),
120.6 (2 × Py), 128.0 (Ar), 128.1 (Ar), 128.5 (Ar), 136.8 (Ar), 137.5
(2 × 2-Cim), 138.5 and 138.6 (Py), 144.6 (2 × 4-Cim), 155.9 (2 × Py),
155.0 and 156.1 (2 × C=O).
Column chromatography was carried out with silica gel 60 (particle
size 0.040–0.063 mm, 230-400 mesh; Merck) and commercially
available solvents. TLC was conducted on aluminum sheets coated
with silica gel 60 F254 obtained from Merck, with visualization by
UV lamp (254 or 360 nm). Melting points (mp) were measured on
a Büchi B-540 melting point apparatus in open capillaries and are
MS (ESI): m/z = 594 (M)+, 616 (M + Na)+.
Anal. Calcd for C33H35N7O4: C, 66.76; H, 5.94; N, 16.52. Found: C,
66.45; H, 6.06; N, 16.21.
2,6-Bis{[4-(1-(1S)-benzyloxycarbonylamino-2-methylpropyl)-
1H-imidazol-1-yl]methyl}pyridine (11b)
1
uncorrected. H and 13C NMR spectra were recorded at 360/500
The title compound was synthesized from 1b and 2,6-bis(bromo-
methyl)pyridine following the general procedure; yield: 201 mg
(62%); pale yellow oil; Rf1 = 0.42 (silica gel; hexane–EtOAc–
MeOH–NH4OH, 3:5:1:0.1); Rf2 = 0.12 (silica gel; acetone–
hexane, 2:1); [a]D22 –27.6 (c 0.5, MeOH).
1H NMR (360 MHz, CDCl3): d = 0.81 [6 H, d, J = 6.4 Hz,
(CH3)2CH], 0.92 [6 H, d, J = 6.4 Hz, (CH3)2CH], 2.09–2.13 [2 H,
m, (CH3)2CH], 4.45–4.49 (2 H, m, 2 × CHNH), 4.99–5.08 (8 H, m,
2 × CH2Py and 2 × CH2Ph), 5.97 (2 H, d, J = 8.7 Hz, 2 × CHNH),
6.76 (2 H, s, 2 × 5-Him), 6.82 (2 H, d, J = 7.4 Hz, Py), 7.25–7.29 (10
H, m, Ar), 7.48 (2 H, s, 2 × 2-Him), 7.57 (1 H, t, J = 7.5 Hz, Py).
13C NMR (90 MHz, CDCl3): d = 18.8 [(CH3)2CH], 19.4
[(CH3)2CH], 33.0 [2 × (CH3)2CH], 52.3 (PyCH2), 55.1 (2 × CH),
66.7 (2 × PhCH2), 116.6 (2 × 5-Cim), 120.4 (2 × Py), 128.0 (Ar),
128.0 (Ar), 128.6 (Ar), 136.9 (Ar), 137.5 (2 × 2-Cim), 138.7 (Py),
142.4 (2 × 4-Cim), 156.2 (2 × Py), 156.4 (2 × C=O).
MHz and 90/125 MHz, respectively, with Bruker AMX 360 or
Bruker Avance 500 instruments at 25 °C. Chemical shifts are re-
1
ported in ppm relative to TMS. Residual solvent signals in the H
and 13C NMR spectra were used as an internal reference (CDCl3:
d = 7.25 and 77.23, CD3OD: d = 3.31 and 49.15). Coupling con-
stants (J) are given in Hz. The phenyl, pyridine, imidazole, and im-
idazolium protons and carbons are marked as Ar, Py, Im, and Im,
respectively. Additional NMR techniques such as 13C-APT, 1H-1H
1
1
COSY, H-13C HMBC, and H-13C HMQC were used for regular
signal assignment. Occasionally, 1H and 13C NMR spectra showed
broad signals or two set of signals without estimated spin-spin inter-
actions as a result of hindered rotation in carbamate function. In
CD3OD solution, a rapid H–D exchange of C2-H of the imidazole
was observed for the target imidazoliophanes. Optical rotation val-
ues were measured on a Perkin–Elmer 341 instrument, concentra-
tion c is given in g/100 mL MeOH. The enantiomeric purity was
verified by measuring 1H NMR spectra with (R)-Mosher acid. The
mass spectra were measured on a LC-MS Micromass Quattro Micro
API (Waters) instrument with a direct input (ESI+, 0.5 mL stream
MeOH, mass range 200–1100; Da and MassLynx software were
used). Reagents and solvents were purchased from Aldrich or Penta
and used without further purification. Anhyd acetone was freshly
prepared prior to use. Starting imidazoles 1a–d and 2 were synthe-
sized according to the literature.9,10For the experimental details and
characterization of compounds 4a, 5b, 6a, c, d, 12a–e, 14, 15, crys-
tal data of 9,18 and representative NMR spectra, see Supporting In-
formation.
MS (ESI): m/z = 650 (M)+, 672 (M + Na)+.
Anal Calcd for C37H43N7O4: C, 68.39; H, 6.67; N, 15.09. Found: C,
67.94; H, 7.11; N, 14.47.
2,6-Bis{[4-(1-(1S)-benzyloxycarbonylamino-3-methylbutyl)-
1H-imidazol-1-yl]methyl}pyridine (11c)
The title compound was synthesized from 1c and 2,6-bis(bromo-
methyl)pyridine following the general procedure; yield: 176 mg
(52%); pale yellow oil; Rf1 = 0.33 (silica gel; hexane–EtOAc–
MeOH–NH4OH, 3:5:1:0.1); Rf2 = 0.76 (silica gel; acetone–
MeOH, 10:1); [a]D22 –30.8 (c 0.5, MeOH).
1H NMR (500 MHz, CDCl3): d = 0.89–0.91 [12 H, m, 2 ×
(CH3)2CH], 1.54–1.56 [2 H, m, 2 × (CH3)2CH], 1.68–1.70 [4 H, m,
2 × (CH3)2CHCH2], 4.74–4.79 (2 H, m, 2 × CHNH), 5.03 (4 H,
ABq, J = 16.2 Hz, 2 × CH2Py), 5.04–5.06 (4 H, m, 2 × CH2Ph), 5.89
(2 H, d, J = 8.4 Hz, CHNH), 6.66 (2 H, s, 5-Him), 6.83 (2 H, d,
J = 7.6 Hz, Py), 7.25–7.28 (10 H, m, Ar), 7.45 (2 H, s, 2-Him), 7.57–
7.59 (1 H, m, Py).
Precyclophanes 11a–e; General Procedure
To a solution of imidazole 1a–d (1.05 mmol) in MeCN (5 mL) was
added 25% aq NaOH (0.5 mL) and the reaction mixture was stirred
for 20 min. 1,3-Bis(bromomethyl)benzene or 2,6-bis(bromometh-
yl)pyridine (0.5 mmol) was added at once and the solution was
stirred at 25 °C for the indicated time until TLC showed that the re-
action was complete. The solvent was evaporated in vacuo, H2O (5
mL) was added, and the mixture was extracted with CH2Cl2 (3 × 5
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3192
A. Marek et al.
PAPER
13C NMR (125 MHz, CDCl3): d = 22.5 [(CH3)2CH], 22.7
[(CH3)2CH], 24.9 [2 × (CH3)2CH], 44.7 [2 × (CH3)2CHCH2], 47.6
(2 × CHNH), 52.2 (2 × PyCH2), 66.5 (2 × PhCH2), 116.0 (2 × 5-
Cim), 120.5 (2 × Py), 127.5 (Ar), 128.1 (Ar), 128.5 (Ar), 136.8 (Ar),
137.7 (2 × 2-Cim), 138.6 (Py), 143.8 (2 × 4-Cim), 156.0 (2 × Py),
156.2 (2 × C=O).
Imidazoliophane 7
The title compound was synthesized from precyclophane 14 and
1,3-bis(bromomethyl)benzene following the general procedure;
yield: 382 mg (95%); white solid; mp 290 °C (dec.).
1H NMR (360 MHz, CD3OD–D2O): d = 5.86 (8 H, s, 4 × CH2N),
6.90 (4 H, d, J = 7.7 Hz, Ar), 7.13 (2 H, t, J = 7.5 Hz, Ar), 7.20 (8
H, d, J = 7.1 Hz, Ar), 7.36 (8 H, t, J = 7.8 Hz, Ar), 7.46 (4 H, t,
J = 7.5 Hz, Ar), 7.52 (2 H, s, Ar), 9.80 (2 H, s, 2 × 2-Him).
13C NMR (90 MHz, CD3OD–D2O): d = 52.2 (4 × CH2N), 126.1
(Ar), 126.7 (Ar), 130.3 (Ar), 130.4 (Ar), 130.7 (Ar), 131.9 (Ar),
132.4 (Ar), 134.4 (Ar), 136.9 (Ar); one signal is missing.
MS (ESI): m/z = 678 (M)+, 701 (M + Na)+.
Anal. Calcd for C39H47N7O4: C, 69.10; H, 6.99; N, 14.46. Found: C,
68.68; H, 7.09; N, 14.07.
2,6-Bis{[4-(1-(1S)-benzyloxycarbonylamino-2-phenylethyl)-
1H-imidazol-1-yl]methyl}pyridine (11d)
MS (ESI): m/z = 725/727 (1:1) (M–Br)+, 645 (M – 2 Br + 1)+, 323.2
The title compound was synthesized from 1d and 2,6-bis(bromo-
methyl)pyridine following the general procedure; yield: 205 mg
(55%); white solid; Rf1 = 0.47 (silica gel; hexane–EtOAc–MeOH–
NH4OH, 3:5:1:0.1); Rf2 = 0.59 (silica gel; acetone–MeOH, 10:1);
mp 75–77 °C; [a]D22 –29.4 (c 0.5, MeOH).
1H NMR (500 MHz, CDCl3): d = 3.11–3.17 (2 H, m, PhCH2CH),
3.23–3.28 (2 H, m, PhCH2CH), 4.93–4.98 (6 H, m, 2 × PhCH2CO
and 2 × CHNH), 5.07 (4 H, ABq, J = 12.3 Hz, 2 × CH2Py), 6.44 (2
H, d, J = 7.5 Hz, 2 × CHNH), 6.49 (2 H, s, 2 × 5-Him), 6.55 (2 H, d,
J = 7.5 Hz, Py), 7.03–7.07 (4 H, m, Ar), 7.10–7.14 (6 H, m, Ar),
7.23–7.27 (10 H, m, Ar), 7.42 (2 H, s, 2 × 2-Him), 7.46 (1 H, t,
J = 7.8 Hz, Py).
(M – 2 Br)2+.
Anal. Calcd for C46H38Br2N4: C, 68.49; H, 4.75; Br, 19.81; N, 6.95.
Found: C, 68.45; H, 4.98; Br, 19.64; N, 6.93.
Imidazoliophane 8
The title compound was synthesized from precyclophane 14 and
2,6-bis(bromomethyl)pyridine following the general procedure;
yield: 338 mg (84%); white solid; mp 290 °C (dec.).
1H NMR (500 MHz, CD3OD–D2O): d = 5.42–5.63 (8 H, m, 4 ×
CH2N), 6.87 (1 H, s, Ar), 6.93 (2 H, d, J = 7.3 Hz, Ar), 7.01 (2 H,
d, J = 7.6 Hz, Ar), 7.04–7.08 (6 H, m, Ar), 9.13 (3 H, t, J = 7.1 Hz,
Ar), 7.25–7.32 (9 H, m, Ar), 7.40–7.44 (3 H, m, Ar), 7.59 (1 H, t,
J = 7.3 Hz, Ar), 9.70 (2 H, s, 2 × 2-Him).
13C NMR (90 MHz, CD3OD–D2O): d = 51.9 (2 × CH2N), 53.2 (2 ×
CH2N), 123.8 (Ar), 124.6 (Ar), 125.6 (Ar), 125.8 (Ar), 129.2 (Ar),
130.2 (Ar), 130.7 (Ar), 131.8 (Ar), 131.8 (Ar), 132.1 (Ar), 133.6
(Ar), 133.7 (Ar), 134.2 (Ar), 132.3 (Ar), 136.8 (Ar), 138.8 (Ar),
139.6 (Py), 154.4 (Py).
13C NMR (125 MHz, CD3OD): d = 30.8 (2 × PhCH2CH), 52.6 (2 ×
CHNH), 52.9 (2 × CH2Py), 67.3 (2 × PhCH2O), 118.2 (2 × 5-Cim),
121.9 (2 × Py), 127.4 (Ar), 128.7 (Ar), 128.9 (Ar), 129.3 (Ar), 129.5
(Ar), 130.6 (Ar), 138.4 (Ar), 139.0 (2 × 2-Cim), 139.7 (Ar), 139.9
(Py), 143.8 (2 × 4-Cim), 157.6 (2 × Py), 158.0 (2 × C=O).
MS (ESI): m/z = 746 (M)+, 769 (M + Na)+.
Anal. Calcd for C45H43N7O4: C, 72.46; H, 5.81; N, 13.15. Found: C,
72.57; H, 5.90; N, 13.29.
MS (ESI): m/z = 726/728 (1:1) (M – Br)+, 646 (M – 2 Br + 1)+, 323.6
(M – 2 Br)2+.
Anal. Calcd for C45H37Br2N5: C, 66.92; H, 4.62; Br, 19.79; N, 8.67.
Found: C, 67.11; H, 4.77; Br, 19.43; N, 8.69.
1,3-Bis[4-(1-(1S)-benzyloxycarbonylaminoethyl)-1H-imidazol-
1-yl]benzene (11e)
The title compound was synthesized from 1a and 1,3-bis(bromo-
methyl)benzene following the general procedure; yield: 181 mg
(61%); pale yellow oil; Rf1 = 0.38 (silica gel; hexane–EtOAc–
MeOH–NH4OH, 3:5:1:0.1); Rf2 = 0.08 (silica gel; acetone–
hexane, 2:1); [a]D22 –15.6 (c 0.5, MeOH).
1H NMR (500 MHz, CDCl3): d = 1.46 (6 H, d, J = 5.5 Hz, 2 ×
CH3CH), 4.82–4.85 (2 H, m, 2 × CHNH), 4.90–4.91 (4 H, m, 2 ×
CH2Nim), 5.04 (4 H, ABq, J = 12.1 Hz, 2 × CH2Ph), 6.12 (2 H, d,
J = 8.1 Hz, 2 × CHNH), 6.69 (2 H, s, 2 × 5-Him), 6.79 (1 H, d,
J = 11.2 Hz, Ar), 7.03 (2 H, d, J = 7.1 Hz, Ar), 7.23–7.28 (11 H, m,
Ar), 7.39 (2 H, s, 2 × 2-Him).
Imidazoliophane 9
The title compound was synthesized from precyclophane 15 and
2,6-bis(bromomethyl)pyridine following the general procedure;
yield: 355 mg (88%); white solid; mp 290 °C (dec.).
1H NMR (360 MHz, CD3OD–D2O): d = 5.62 (8 H, s, 4 × CH2N),
7.07–7.14 (12 H, m, Ar), 7.31 (8 H, t, J = 7.7 Hz, Ar), 7.44 (4 H, t,
J = 7.4 Hz, Ar), 7.59 (2 H, t, J = 7.7 Hz, Ar), 9.55 (2 H, s, 2 × 2-
Him).
13C NMR (90 MHz, CD3OD–D2O): d = 52.9 (4 × CH2N), 123.8
(Ar), 126.0 (Ar), 130.1 (Ar), 131.7 (Ar), 131.7 (Ar), 133.6 (Ar),
139.3 (Ar), 139.6 (Ar), 154.3 (Py).
13C NMR (125 MHz, CDCl3): d = 21.4 (2 × CH3CH), 45.0 (2 × CH),
50.2 (2 × NimCH2), 66.2 (2 × PhCH2), 115.0 (2 × 5-Cim), 125.9 (Ar),
127.0 (Ar), 127.8 (Ar), 127.9 (Ar), 128.3 (Ar), 129.5 (Ar), 136.6
(Ar), 137.0 (Ar), 137.1 (2 × 2-Cim), 144.5 (2 × 4-Cim), 155.7 (C=O).
MS (ESI): m/z = 727/729 (1:1) (M – Br)+, 647 (M – 2 Br + 1)+, 323.9
(M – 2 Br)2+.
Anal. Calcd for C44H36Br2N6: C, 65.36; H, 4.49; Br, 19.76; N, 10.39.
Found: C, 65.32; H, 4.73; Br, 19.74; N, 10.21.
MS (ESI): m/z = 593 (M)+, 616 (M + Na)+.
Anal. Calcd for C34H36N6O4: C, 68.90; H, 6.12; N, 14.18. Found: C,
68.52; H, 6.53; N, 13.78.
Imidazoliophane 10a
The title compound was synthesized from precyclophane 11a and
2,6-bis(bromomethyl)pyridine following the general procedure;
yield: 394 mg (92%); white solid; mp 154–157 °C; [a]D22 –9.6 (c 1,
MeOH).
1H NMR (500 MHz, CD3OD): d = 1.41 (3 H, d, J = 6.9 Hz,
CH3CH), 1.44 (3 H, d, J = 6.9 Hz, CH3CH), 4.70–4.71 (1 H, q,
J = 6.8 Hz, CHNH), 4.78–4.79 (1 H, q, J = 6.8 Hz, CHNH), 4.97–
4.99 (4 H, m, CH2Ph), 5.49–5.57 (8 H, m, 4 × CH2Py), 7.25–7.36
(10 H, m, Ar), 7.44 (2 H, t, J = 7.5 Hz, Py), 7.59 (2 H, s, 2 × 5-Him),
Imidazoliophanes 7–9 and 10a–e; General Procedure
To a solution of precyclophane (0.5 mmol) in anhyd acetone (15
mL) was added 1,3-bis(bromomethyl)benzene or 2,6-bis(bromo-
methyl)pyridine (0.5 mmol) at once and the reaction mixture was
heated at reflux under argon atmosphere for the indicated time. Af-
ter completion of the reaction as monitored on TLC (silica gel, hex-
ane–EtOAc–MeOH–NH4OH, 3:5:1:0.1), the imidazoliophane was
collected by filtration, thoroughly washed with EtOAc–hexane
(3:1), and dried in vacuo.
Synthesis 2010, No. 18, 3188–3194 © Thieme Stuttgart · New York

PAPER
Dicationic Imidazoliophanes
3193
7.62–7.65 (2 H, m, Py), 7.74–7.89 (1 H, m, Py), 7.97 (1 H, t, J = 7.7
Hz, Py), 9.04 (2 H, s, 2 × 2-Him).
Imidazoliophane 10d
The title compound was synthesized from precyclophane 11d and
2,6-bis(bromomethyl)pyridine following the general procedure;
yield: 494 mg (98%); mp 148–151 °C; [a]D22 –44.0 (c 0.1, MeOH).
13C NMR (90 MHz, CD3OD): d = 20.1 (2 × CH3CH), 42.6 and 42.7
(2 × CHNH), 52.3 (2 × PyCH2), 54.5 (2 × PyCH2), 67.8 (2 ×
PhCH2), 122.0 and 122.1 (2 × 5-Cim), 124.1 (2 × Py), 124.5 (2 × Py),
129.0 and 129.1 (Ar), 129.3 (Ar), 129.7 (Ar), 138.2 and 138.5 (Ar),
139.5 and 139.6 (2 × 4-Cim), 140.1 and 141.1 (2 × 2-Cim), 140.3 and
140.3 (2 × Py), 154.2 (2 × Py), 154.5 and 154.6 (2 × Py), 157.5 (2 ×
C=O).
1H NMR (500 MHz, CD3OD): d = 3.06–3.11 (4 H, m, 2 ×
PhCH2CH), 4.83 (4 H, ABq, J = 12.5 Hz, 2 × PhCH2CO), 4.91–
4.95 (2 H, m, 2 × CHNH), 5.38 (4 H, ABq, J = 16.5 Hz, 2 ×
a
b
CH2 Py), 5.50–5.56 (4 H, m, CH2 Py), 7.07–7.10 (4 H, m, Ar),
7.13–7.16 (4 H, m, Ar), 7.18–7.21 (6 H, m, Ar), 7.26–7.28 (6 H, m,
Ar), 7.46 (2 H, d, J = 6.3 Hz, Py), 7.65 (2 H, d, J = 7.3 Hz, Py), 7.8
(2 H, s, 2 × 5-Him), 7.85 (1 H, t, J = 7.6 Hz, Py), 8.0 (1 H, t, J = 7.5
Hz, Py), 8.87 (2 H, s, 2 × 2-Him).
MS (ESI): m/z = 777–779 (1:1) (M – Br)+, 697 (M – 2 Br + 1)+,
349.3 (M – 2 Br)2+.
Anal. Calcd for C40H42Br2N8O4: C, 55.95; H, 4.93; Br, 18.61; N,
13.05. Found: C, 55.59; H, 5.15; Br, 18.24; N, 12.57.
13C NMR (125 MHz, CD3OD): d = 40.5 (2 × PhCH2CH), 48.4 (2 ×
CHNH), 52.3 (2 × CH2Pya), 54.6 (2 × CH2Pyb), 67.7 (2 ×
PhCH2CO), 122.3 and 122.6 (2 × 5-Cim), 124.2 (2 × Py), 124.5 (2 ×
Py), 128.2 (Ar), 128.8 (Ar), 129.2 (Ar), 129.5 (Ar), 129.6 (Ar),
129.7 (Ar), 130.6 (Ar), 137.4 (2 × 4-Cim), 137.9 (Ar), 138.0 (Ar),
140.2 (2 × 2-Cim), 140.5 (2 × Py), 154.0 (2 × Py), 154.5 (2 × Py),
157.8 (2 × C=O).
Imidazoliophane 10b
The title compound was synthesized from precyclophane 11b and
2,6-bis(bromomethyl)pyridine following the general procedure;
yield: 374 mg (82%); mp 147–151 °C; [a]D22 –10.5 (c 1, MeOH).
1H NMR (500 MHz, CD3OD): d = 0.53 [3 H, d, J = 5.8 Hz,
(CH3)2CH], 0.69 [3 H, d, J = 5.6 Hz, (CH3)2CH], 0.88–0.92 [6 H,
m, (CH3)2CH], 2.01–2.06 [2 H, m, (CH3)2CH], 4.29–4.32 (2 H, m,
2 × CHNH), 5.00–5.06 (4 H, m, 2 × CH2Ph), 5.50–5.67 (8 H, m, 4
× CH2Py), 7.32–7.36 (10 H, m, Ar), 7.53 (1 H, s, 5-Him), 7.59–7.60
(2 H, m, Py), 7.64–7.65 (2 H, m, Py and 5-Him), 7.70–7.78 (1 H, m,
Py), 7.57 (1 H, t, J = 7.0 Hz, Py), 9.04 (2 H, s, 2 × 2-Him).
MS (ESI): m/z = 929/931 (1:1) (M – Br)+, 849 (M – 2 Br + 1)+, 425.2
(M – 2 Br)2+.
Anal. Calcd for C52H50Br2N8O4: C, 61.79; H, 4.99; Br, 15.81; N,
11.09. Found: C, 61.44; H, 5.36; Br, 15.52; N, 10.71.
Imidazoliophane 10e
The title compound was synthesized from precyclophane 11e and
1,3-bis(bromomethyl)benzene following the general procedure;
yield: 325 mg (76%); white solid; mp 160–170 °C; [a]D22 –5.7 (c
0.5, MeOH).
1H NMR (500 MHz, CD3OD): d = 1.37 (3 H, d, J = 6.7 Hz,
CH3CH), 1.45 (3 H, d, J = 6.8 Hz, CH3CH), 4.70–4.73 (1 H, q,
J = 7.0 Hz, CHNH), 4.78–4.82 (1 H, q, J = 6.9 Hz, CHNH), 4.90–
5.00 (4 H, m, 2 × CH2Ph), 5.37–5.50 (8 H, m, 4 × CH2Ph), 6.63–
6.66 (1 H, m, Ph), 7.06–7.08 (1 H, m, Ph), 7.26–7.30 (10 H, m, Ar),
7.39–7.43 (3 H, m, Ph), 7.50–7.54 (1 H, m, Ph), 7.57–7.60 (2 H, m,
Ph), 7.68 (1 H, s, 5-Him), 7.71 (1 H, s, 5-Him), 9.32 (1 H, s, 2-Him),
9.40 (1 H, s, 2-Him).
13C NMR (90 MHz, CD3OD): d = 19.0 and 19.1 [(CH3)2CH], 20.5
and 20.6 [(CH3)2CH], 32.9 and 33.0 [2 × (CH3)2CH], 52.4 and 52.5
(2 × PyCH2), 52.9 (2 × CH), 54.4 and 54.6 (2 × PyCH2), 68.0 (2 ×
PhCH2), 122.0 and 122.5 (2 × 5-Cim), 124.5 (2 × Py), 124.7 (2 × Py),
129.0 (Ar), 129.4 (Ar), 129.7 (Ar), 137.6 and 138.0 (Ar), 139.0 and
139.1 (2 × 4-Cim), 140.3 (2 × 2-Cim), 140.5 (2 × Py), 154.3 (2 × Py),
154.4 (2 × Py), 154.5 (2 × Py), 158.3 and 158.4 (2 × C=O).
MS (ESI): m/z = 833/835 (1:1) (M – Br)+, 753 (M – 2 Br + 1)+, 377.1
(M – 2 Br)2+.
Anal. Calcd for C44H50Br2N8O4: C, 57.77; H, 5.51; Br, 17.47; N,
12.25. Found: C, 57.40; H, 5.43; Br, 17.15; N, 11.67.
13C NMR (125 MHz, CD3OD): d = 19.9 and 20.0 (2 × CH3CH), 42.6
(2 × CHNH), 51.5 (2 × PhCH2), 53.7 (2 × PhCH2), 67.8 (2 ×
PhCH2), 122.4 (2 × 5-Cim), 124.7 and 125.0 (2 × Ph), 126.5 and
126.6 (2 × Ph), 128.8 (Ar), 129.2 (Ar), 129.7 (Ar), 129.8 (Ar), 129.9
(Ar), 130.6 (Ar), 130.9 (Ar), 131.2 (Ar), 136.2 and 136.5 (Ar),
137.4 (Ar), 138.1 and 138.2 (Ar), 139.0 and 139.1 (2 × 2-Cim),
157.5 (2 × C=O).
Imidazoliophane 10c
The title compound was synthesized from precyclophane 11c and
2,6-bis(bromomethyl)pyridine following the general procedure;
yield: 399 mg (85%); white solid; mp 125–128 °C; [a]D22 –28.5 (c
1, MeOH).
1H NMR (500 MHz, CD3OD): d = 0.78–0.91 [12 H, m, 2 ×
(CH3)2CH], 1.54–1.58 [4 H, m, 2 × (CH3)2CHCH2], 2.02–2.06 [2 H,
m, 2 × (CH3)2CH], 4.67–4.70 (2 H, m, 2 × CHNH), 4.92–5.02 (4 H,
m, 2 × CH2Ph), 5.53–5.64 (8 H, m, 8 × CH2Py), 7.30–7.38 (12 H,
m, Ar and Py), 7.53–7.70 (4 H, m, Py and 2 × 5-Him), 7.78–7.99 (2
H, m, Py), 9.03 (2 H, s, 2 × 2-Him).
MS (ESI): m/z = 775/777 (1:1) [M+ – Br].
Anal. Calcd for C42H44Br2N6O4: C, 58.89; H, 5.18; Br, 18.66; N,
9.81. Found: C, 58.61; H, 5.36; Br, 18.32; N, 9.66.
13C NMR (125 MHz, CD3OD): d = 21.8 and 23.4 [2 × (CH3)2CH],
25.8 [2 × (CH3)2CH], 43.4 [2 × (CH3)2CHCH2], 44.9 (2 × CHNH),
52.4 (2 × PyCH2), 54.6 (2 × PyCH2), 67.8 (2 × PhCH2), 121.8 and
122.2 (2 × 5-Cim), 124.2 (2 × Py), 124.5 and 124.6 (2 × Py), 128.9
(Ar), 129.3 (Ar), 129.7 (Ar), 138.1 and 138.3 (Ar), 139.3 (2 × 4-
Cim), 140.1 (2 × 2-Cim), 140.4 (2 × Py), 154.2 (2 × Py), 154.3 and
154.5 (2 × Py), 158.0 (2 × C=O).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
This research was supported by the Ministry of Education, Youth
and Sport (MSM 0021627501) and by the Czech Science Foundati-
on (203/07/P013).
MS (ESI): m/z = 861/863 (1:1) (M – Br)+, 781 (M – 2 Br + 1)+, 391.3
(M – 2 Br)2+.
Anal. Calcd for C46H54Br2N8O4: C, 58.60; H, 5.77; Br, 16.95; N,
11.89. Found: C, 58.44; H, 5.98; Br, 16.67; N, 11.57.
References
(1) Gibson, S. E.; Lecci, C. Angew. Chem. Int. Ed. 2006, 45,
1364.
Synthesis 2010, No. 18, 3188–3194 © Thieme Stuttgart · New York

3194
A. Marek et al.
PAPER
(2) Katritzky, A. R.; Pozharskii, A. F. Handbook of
Heterocyclic Chemistry; Elsevier: Oxford, 2000, 2nd ed.,
91–140.
(3) (a) Plaquevent, J.-C.; Levillain, J.; Guillen, F.; Malhiac, C.;
Gaumont, A.-C. Chem. Rev. 2008, 108, 5035. (b) Martins,
M. A. P.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.;
Bonacorso, H. G. Chem. Rev. 2008, 108, 2015. (c)Mlostoń,
G.; Romański, J.; Jasiński, M.; Heimgartner, H.
Tetrahedron: Asymmetry 2009, 20, 1073.
(12) (a) You, J.-S.; Yu, X.-Q.; Zhang, G.-L.; Xiang, Q.-X.; Lan,
J.-B.; Xie, R.-G. Chem. Commun. 2001, 1816.
(b) Haberhauer, G. Angew. Chem. Int. Ed. 2007, 46, 4397.
(13) (a) Alcalde, E.; Mesquida, N.; Pérez-García, L. Eur. J. Org.
Chem. 2006, 3988. (b) Alcade, E.; Alvarez-Rúa, C.; García-
Granda, S.; García-Rodriguez, E.; Mesquida, N.; Pérez-
García, L. Chem. Commun. 1999, 295. (c) Yuan, Y.; Gao,
G.; Jiang, Z.-L.; You, J.-S.; Zhou, Z.-Y.; Yuan, D.-Q.; Xie,
R.-G. Tetrahedron 2002, 58, 8993.
(4) (a) De Luca, L. Curr. Med. Chem. 2006, 13, 1. (b) Boiani,
M.; González, M. Mini-Rev. Med. Chem. 2005, 5, 409.
(5) (a) Bureš, F.; Kulhánek, J. Tetrahedron: Asymmetry 2005,
16, 1347. (b) Bureš, F.; Szotkowski, T.; Kulhánek, J.;
Pytela, O.; Ludwig, M.; Holčapek, M. Tetrahedron:
Asymmetry 2006, 17, 900. (c) Sívek, R.; Pytela, O.; Bureš,
F. J. Heterocycl. Chem. 2008, 45, 1621. (d) Sívek, R.;
Pytela, O.; Kulhánek, J.; Bureš, F. Molecules 2008, 13,
2326. (e) Mucha, P.; Mlostoń, G.; Jasiński, M.; Linden, A.;
Heimgarten, H. Tetrahedron: Asymmetry 2008, 19, 1600.
(6) Kühl, O. Chem. Soc. Rev. 2007, 36, 592.
(7) (a) Kulhánek, J.; Bureš, F.; Pytela, O.; Mikysek, T.; Ludvík,
J.; Růžička, A. Dyes Pigm. 2010, 85, 57. (b) Bureš, F.;
Kulhánek, J.; Mikysek, T.; Ludvík, J.; Lokaj, J. Tetrahedron
Lett. 2010, 51, 2055.
(8) Coppola, G. M.; Schuster, H. F. Asymmetric Synthesis:
Construction of Chiral Molecules Using Amino Acids;
Wiley: New York, 1987.
(14) (a) Rajakumar, P.; Rajhiman, R.; Selvam, S.; Rengasamy,
R.; Nagaraj, S. Bioorg. Med. Chem. Lett. 2009, 19, 3466.
(b) Rajakumar, P.; Sekar, K.; Shanmugaiah, V.; Mathivanan,
N. Bioorg. Med. Chem. Lett. 2008, 18, 4416.
(15) (a) Baker, M. V.; Brown, D. H.; Simpson, P. V.; Skelton, B.
W.; White, A. H. Dalton Trans. 2009, 7294. (b) Barnard, P.
J.; Baker, M. V.; Bernes-Price, S. J.; Skelton, B. W.; White,
A. H. Dalton Trans. 2004, 1038. (c) Baker, M. V.; Brown,
D. H.; Haque, R. A.; Skelton, B. W.; White, A. H. Dalton
Trans. 2004, 3756. (d) Garrison, J. C.; Simons, R. S.; Talley,
J. M.; Tessier, C. A.; Youngs, W. J. Organometallics 2001,
20, 1276. (e) Garrison, J.; Simons, R. S.; Kofron, W. G.;
Tessier, C. A.; Youngs, W. J. Chem. Commun. 2001, 1780.
(f) Magill, A. M.; McGuinness, D. S.; Cavell, K. J.;
Britovsek, G. J. P.; Gibson, V. C.; White, A. J. P.; Williams,
D. J.; White, A. H.; Skelton, B. W. J. Organomet. Chem.
2001, 617-618, 546.
(16) Rajakumar, P.; Dhanasekaran, M. Tetrahedron 2002, 58,
1355.
(9) Marek, A.; Kulhánek, J.; Ludwig, M.; Bureš, F. Molecules
2007, 12, 1183.
(17) (a) Baker, M. V.; Bosnich, M. J.; Brown, D. H.; Byrne, L. T.;
Hesler, V. J.; Skelton, B. W.; White, A. H.; Williams, C. C.
J. Org. Chem. 2004, 69, 7640. (b) Bitter, I.; Török, Z.;
Csokai, V.; Grün, A.; Balázs, B.; Tóth, G.; Keserü, G. M.;
Kovári, Z.; Czugler, M. Eur. J. Org. Chem. 2001, 2861.
(18) CCDC 757647 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: +44(1223)336033, E-mail:
deposit@ccdc.cam.ac.uk].
(10) Marek, A.; Kulhánek, J.; Bureš, F. Synthesis 2009, 325.
(11) (a) Zhang, X. X.; Brandshaw, J. S.; Izatt, R. M. Chem. Rev.
1997, 97, 3313. (b) Rajakumar, P.; Selvam, S. S.;
Dhanasekaran, M. Tetrahedron Lett. 2005, 46, 6127.
(c) Galindo, F.; Becerril, J.; Burguete, M. I.; Luis, S. V.;
Vigara, L. Tetrahedron Lett. 2004, 45, 1659. (d) Chen, Y.;
Gao, M.; Tan, S.; Reibenspies, J. H.; Zingaro, R. A.
Heterocycles 2009, 78, 891. (e) Rajakumar, P.; Srisailas, M.
Tetrahedron Lett. 2002, 43, 1909.
Synthesis 2010, No. 18, 3188–3194 © Thieme Stuttgart · New York