Synthesis of planar chiral carbazole derivatives bearing a [2.2]paracyclophane skeleton

Article abstract of DOI:10.1002/ijch.201100070

The synthesis of planar chiral carbazoles bearing a [2.2]paracyclophane backbone is described. Starting from readily available 4-bromo[2.2] paracyclophane planar chiral carbazoles are obtained in a two-step synthesis by Pd-catalyzed C-N cross-coupling and

Full text of DOI:10.1002/ijch.201100070

Full Paper
DOI: 10.1002/ijch.201100070
Synthesis of Planar Chiral Carbazole Derivatives Bearing a
[2.2]Paracyclophane Skeleton
Petra Lennartz,[a] Gerhard Raabe,[a] and Carsten Bolm*[a]
Abstract: The synthesis of planar chiral carbazoles bearing a
[2.2]paracyclophane backbone is described. Starting from
readily available 4-bromo[2.2]paracyclophane planar chiral
carbazoles are obtained in a two-step synthesis by Pd-cata-
lyzed CÀN cross-coupling and subsequent oxidative cycliza-
tion.
Keywords: carbazoles · cyclophanes · oxidative cyclization · palladium · planar chirality
1. Introduction
useful for the preparation of heterocycles including carba-
zoles.[11]
In continuation of our studies on the synthesis of disub-
Since the first directed synthesis of [2.2]paracyclophane
(1a, Figure 1) by Cram and Steinberg in 1951[1] there has
been an ongoing interest in the unique chemistry of this
stituted [2.2]paracyclophanes[7f–h,9c,12] we became interest-
ed in planar chiral carbazoles such as 2a (Figure 1),
which we hypothesized to be relevant for polymer and
materials science due to the extended p-system of the car-
bazole core.[13] From a synthetic point of view, their prep-
aration by metal-catalyzed direct functionalization/aryla-
tion was expected to provide new insights and opportuni-
ties in the chemistry of [2.2]paracyclophane modifica-
tions.
Figure 1. [2.2]Paracyclophane (1a) and planar chiral carbazole 2a.
class of compounds.[2] In general, [2.2]paracyclophanes
have two benzene rings, which are connected by two eth-
ylene bridges, resulting in a boat-like shape of the
arenes.[3] Aryl substitution can lead to planar chiral com-
pounds, which have successfully been applied as ligands,
auxiliaries or catalysts in stereoselective reactions.[4] Al-
though many [2.2]paracyclophanes with heterocyclic sub-
stituents have been described,[5] only a few compounds
with heterocycles fused to one of the benzene rings are
known.[5,6] This may not be surprising considering that the
synthesis of 4,5-disubstituted [2.2]paracyclophanes is
2. Results
Carbazoles 2 were envisaged to be accessible by two ap-
proaches: First, direct ortho-arylation of amide 4 fol-
lowed by intramolecular oxidative CÀN bond formation
(Scheme 1, path a),[14] or, second, via diarylamine 5 and
subsequent oxidative CÀC coupling reaction (path b).[15]
Initial attempts to directly arylate 4-amido-
[2.2]paracyclophanes 4 (with R1 =OtBu or Et; Scheme 1,
path a) under conditions similar to those reported for the
direct arylation of anilides[16] remained unsuccessful. It
was therefore decided to follow path b (Scheme 1). As
first step diarylamine syntheses by palladium-catalyzed
mainly
restricted
to
the
use
of
4-hydroxy-
[2.2]paracyclophane derivatives as starting materials.[7,8]
Regioisomeric mixtures have often been obtained when
other monosubstituted [2.2]paracyclophanes were ap-
plied.[9] For the functionalization of more “classical”
arenes efficient ortho-directing groups have been found,
which opened new pathways for metal-catalyzed direct
CÀH arylations.[10] Both inter- and intramolecular cou-
pling reactions have been developed, and among the
latter oxidative biaryl couplings have proved particularly
[a] P. Lennartz, G. Raabe, C. Bolm
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, 52056 Aachen (Germany)
phone: +49 241 80 94675
fax: +49 241 8092391
e-mail: carsten.bolm@oc.rwth-aachen.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/ijch.201100070.
Isr. J. Chem. 2012, 52, 171 – 179
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171

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P. Lennartz et al.
tries 3 and 4), and neither raising the temperature nor ex-
tending the reaction time improved the results (entries 5–
7). Two other ligands, BINAP and dicyclohexylphosphi-
no-2’,6’-dimethoxybiphenyl (S-Phos), were tested. In the
presence of BINAP no product was formed, and when S-
Phos was used similar results than obtained with X-Phos
(entries 8,9) were achieved. Noteworthy, in the absence
of a ligand no product was formed (entry 10).
Under the optimized reaction conditions, both elec-
tron-rich (R=Me, iPr) and electron-poor (R=F, CF3,
CO2Me) anilines could be coupled to the [2.2]paracyclo-
phane backbone in good to excellent yields (Table 2, en-
tries 1–7). Attempts to directly couple 2-aminophenol
failed. However, after protection of the hydroxyl group
with triisopropylsilyl chloride,[20] the corresponding
amino[2.2]paracyclophane 5h was formed in 64% yield
(entry 8).
With phenylamino[2.2]paracyclophanes 5a–h in hand
their oxidative cyclizations to give the corresponding car-
bazoles 2a–h were investigated. Amine 5a was chosen as
model compound (Table 3). Initial studies were conduct-
Scheme 1. Retrosynthetic approaches to carbazoles 2.
Buchwald–Hartwig aminations were investigated. Al-
though such cross-couplings are common for CÀN bond
formations,[17] only a few examples of this reaction using
[2.2]paracyclophanes as aryl components are known.[6c,d,18]
Moreover, to the best of our knowledge, only a single
report covered the use of aniline derivatives as N-nucleo-
philes.[6h] For our study, the readily available 4-bromo-
[2.2]paracyclophane (1b, Scheme 1)[19] was chosen as aryl
halide. Although 1b can also be prepared in its enantio-
merically pure form,[7b,18b] each experiment reported here
was carried out using racemic substrates. In the presence
of NaOtBu as base and aniline (6a) as nitrogen nucleo-
phile, 4-N-(phenyl)amino[2.2]paracyclophane (5a) was
formed in good yields within 4 h using Pd2(dba)3 and 2-di-
ed using
a
stoichiometric amount of Pd(OAc)2
(1 equiv)[21] and acetic acid (AcOH) as solvent. With air
as oxidant, carbazole 2a was formed in 61% yield
Table 2. Pd-catalyzed
CÀN
cross-coupling
of
4-bromo-
[2.2]paracyclophane (1b) with anilines 6.[a]
cyclohexylphosphino-2’,4’,6’-triisopropylbiphenyl
(X-
Phos) as ligand in toluene (Table 1, entries 1–7). Starting
with 5 mol% of Pd2(dba)3 and 15% of the ligand the
product was formed in 79% yield. A brief screening of
the reaction conditions revealed that a reduction of the
Pd2(dba)3 loading to 3 mol% was possible (entry 2). With
less than 3 mol% of Pd2(dba)3 the yield decreased (en-
Entry
1
Product/yield
Entry
5
Product/yield
Table 1. Optimization of the Pd-catalyzed CÀN cross-coupling of 4-
bromo[2.2]paracyclophane (1b) with aniline (6a).
2
3
6
7
Entry
Pd2(dba)3/ligand
(mol%)
Ligand
t
T
(8C)
Yield
(%)
(h)
1
2
3
4
5
6
7
8
5/15
3/9
2/6
1/3
1/3
1/3
1/3
3/9
3/9
3/0
X-Phos
X-Phos
X-Phos
X-Phos
X-Phos
X-Phos
X-Phos
S-Phos
BINAP
–
4
4
4
75
75
75
75
75
100
100
75
75
75
79
81
66
45
51
68
68
78
0
4
4
8
16
16
24
4
4
4
[a] Reaction conditions: 1b (1.0 equiv), aniline derivative
6
9
10
(1.2 equiv), Pd2(dba)3 (0.03 equiv), X-Phos (0.09 equiv), NaOtBu
0
(1.4 equiv) in toluene (4 mLmmolÀ1 of 1b) at 758C.
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Synthesis of Planar Chiral Carbazole Derivatives Bearing a [2.2]Paracyclophane Skeleton
Table 3. Optimization of the oxidative cyclization of 4-N-
(phenyl)amino[2.2]paracyclophane (5a).[a]
Entry
Solv.
Pd(OAc)2
(mol%)
Oxidant
Yield
(%)
1
2
3
4
5
6
7
8
9
AcOH
AcOH
AcOH[c]
AcOH[d]
PivOH
TFA
100
20
20
20
20
20
20
20
20
air
air
air
air
air
air
61[b]
49
35
22
traces
0
traces
0
DMF
O2 (1 atm)
O2 (1 atm)
air
DMSO
AcOH/
toluene
AcOH[e]
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
42
Figure 2. Structure of racemic 2a in the solid state.
10
11
12
13
14
15
16
17
18
20
20
20
20
20
20
20
20
10
air
35
35
37
13
0
O2 (1 atm)
benzoquinone
K2S2O8
(entry 2). Increasing the reaction time or decreasing the
temperature resulted in lower yields (entries 3 and 4). In
the absence of Pd(OAc)2 no product was formed. In a
control experiment it was shown that 2a was not stable
under the reaction conditions (AcOH, 10 mol% of
Pd(OAc)2, 1208C). After 24 h only 45% of 2a was recov-
ered. Unfortunately, the decomposition products could
not be identified. To avoid the harsh reaction conditions
and the decomposition of 2a several solvents were tested
(entries 5–8). Whereas in pivalic acid (PivOH), DMF and
DMSO no reaction took place or only traces of 2a were
formed, use of trifluoroacetic acid led to complete de-
composition of 5a (entry 6). To increase the solubility of
5a a 1:1 mixture of AcOH/toluene was tested, but no pos-
itive influence on the reaction outcome was observed
(entry 9). Also the presence of water did not affect the re-
action. Neither the addition of molecular sieves (entry 10)
nor the use of dry acetic acid improved the previous re-
sults. Next, the oxidant was varied. Oxygen, benzoqui-
none, K2S2O8, PhI(OAc)2, Cu(OAc)2 and AgOAc were
tested (entries 11–16), but none was superior to air.
Direct introduction of the oxidant air into the solution
led to full conversion of 5a after only 8 h, and carbazole
2a was obtained in 60% yield (Table 3, entry 17). A de-
crease of the amount of Pd(OAc)2 to 10 mol% lowered
the yield of 2a to 29% (entry 18).
PhI(OAc)2
Cu(OAc)2
AgOAc
air[f]
0
25
60
29
air[f]
[a] The reactions were performed in a 10 mL round bottom flask
using 0.4 mmol of 5a and 4 mL of the given solvent. [b] For 2 h.
[c] At 1008C. [d] For 18 h. [e] Molecular sieve 4 ꢁ (50 mg) was
added. [f] Air was introduced into the solution, and the reaction
time was reduced to 8 h.
(entry 1). The regioselectivity of the oxidative CÀC bond
formation was confirmed by H and 13C NMR spectrosco-
1
py as well as X-ray crystal structure analysis. For the
latter, single crystals of 2a were obtained from a ben-
zene/pentane solvent mixture. An ORTEP plot of 2a is
given in Figure 2. The [2.2]paracylophane unit of the mol-
ecule shows the typical structural features of this class of
compounds. Thus both phenyl rings deviate significantly
from planarity, and the sum of bond angles in the rings
amount to about 7178. The deviation of the para carbon
atoms (C18, C21 and C8, C11) from the least squares
plane defined by the remaining four atoms of each ring
(C16, C17, C19, C20 and C7, C9, C10, C12) is 0.15–
0.16 ꢀ. These values coincide with the one obtained for
parent [2.2]paracyclophane in an ab initio calculation
(MP2/6-31+G*).[9c] The exocyclic C6H5N unit, which
forms a carbazole moiety with one of the aromatic rings
of the [2.2]paracyclophane, is essentially planar, and no
atom of this group deviates from the best plane defined
by its atoms (N, C1–C6) by more than 0.02 ꢀ.
Because additives had a positive impact on the catalyst
performance in other CÀH activation processes,[14c,22,23]
and with the goal to further improve the yield of 2a, the
effects of various acids and donor ligands on the oxidative
cyclizations of 5a under the optimized conditions were
examined (Table 4). Whereas the presence of trifluorace-
tic acid, 1,10-phenanthroline, X-Phos and S-Phos blocked
the catalysis or led to a lower yield of 2a (entries 1–4),
addition of pivalic acid and 3,4,5-trifluorobenzoic acid
(TFBA) resulted in an improvement (entries 5–8). Hence,
Encouraged by this first result (Table 3, entry 1), the
catalyst loading was reduced. In the presence of 20 mol%
of Pd(OAc)2 5a was formed in 49% yield after 14 h
Isr. J. Chem. 2012, 52, 171 – 179
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173

Full Paper
P. Lennartz et al.
Table 4. Effect of additives on the oxidative cyclization of 4-N-
Table 5. Scope of the oxidative cyclization.[a]
phenylamino[2.2]paracyclophane (5a).[a]
Entry
Pd(OAc)2
(mol%)
Additive
(mol%)
Yield (%)
of 2a
1
2
3
4
5
6
7
8
10
10
10
10
10
10
20
10
trifluoroacetic acid (30)
1,10-phenanthroline (10)
X-Phos (15)
S-Phos (15)
pivalic acid (30)
pivalic acid (30)
pivalic acid (60)
3,4,5-trifluorobenzoic acid (30)
0
0
0
25
30
37[b]
62
50
Entry
1
Product/yield
Entry
5
Product/yield
[a] The reactions were performed on a 0.4 mmol scale in a 10 mL
Schlenk tube with 4 mL of AcOH at 1208C for 8 h, and compressed
air was introduced into the solution. [b] Reaction time of 30 h.
2
3
6
7
the best yields of 2a was observed, when either 30 mol%
of TFBA (with 10 mol% of Pd(OAc)2) or 60 mol% of
pivalic acid (with 20 mol% of Pd(OAc)2) were present in
the reaction mixture (Table 4, entries 7 and 8). Then, the
yields for 2a were 50% and 62%, respectively, which
compared well to the 29% yield under identical condi-
tions in the absence of an additive (Table 3, entry 18).
Hypothesizing that a N-substituted product was more
stable under the oxidative reaction condition, N-methy-
lated diaryl amine 7a was submitted to the palladium cat-
alysis (Scheme 2). However, no CÀC bond formation oc-
curred, and the corresponding carbazole 8a was not de-
tected.
4
8
[a] Reaction conditions: Aryl [2.2]paracyclophanyl amines 5a–h
(0.4 mmol), Pd(OAc)2 (0.2 equiv), pivalic acid (0.6 equiv) in acetic
acid (4 mL) at 1208C for 8 h; compressed air was introduced into
the solution. [b] Use of Pd(OAc)2 (10 mol%) and TFBA (30 mol%)
as additive.
due to steric reasons only a single regioisomer (2 f) was
observed starting from amine 5 f.[15b,24]
As demonstrated before, the Pd(OAc)2/TFBA combi-
nation could also be used, but generally this catalyst
system led to lower yields as compared to the application
of 20% and 60% of Pd(OAc)2 and pivalic acid, respec-
tively (Table 5, entries 1, 5 and 7).
Scheme 2. Attempted conversion of N-methylated [2.2]paracyclo-
phanyl amine (7a) into the corresponding carbazole 8a.
Next, the substrate scope was investigated (Table 5).
On the basis of the previous results, the catalysis reac-
tions were performed under conditions as described in
Table 4, entry 7, using 60 mol% of pivalic acid as addi-
tive. To our delight, all aryl [2.2]paracyclophanyl amines
(5b–h) underwent oxidative cyclizations providing the
corresponding planar chiral carbazoles 2b–h in moderate
to good yields. Even the sterically more hindered ortho-
substituted substrates 5g and 5h reacted well, and carba-
zoles 2g and 2h were obtained in similar yields than un-
substituted 2a (entries 7 and 8 versus entry 1). Electronic
variations of the aryl core had a more pronounced impact
and both electron-rich (2b, 2c and 2 f; entries 2, 3 and 6)
as well as electron-poor carbazoles (2d and 2e; entries 4
and 5) were only formed in moderate yields. Probably
3. Summary
An access to carbazoles with fused [2.2]paracyclophane
skeletons has been developed. The reaction sequence is
short and involves only two palladium-catalyzed synthetic
steps. Starting from 4-bromo[2.2]paracyclophane (1b)
Buchwald-Hartwig aminations provide intermediates that
undergo aerobic oxidative cyclizations leading to the tar-
geted carbazoles in moderate to good yields. Although
the catalyst loading in the second step is still high (10–
20 mol%), the general strategy is appealing due to the
conceptional simplicity of the one-step double CÀH acti-
vation/functionalization. The expertise gained in these in-
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Isr. J. Chem. 2012, 52, 171 – 179

Synthesis of Planar Chiral Carbazole Derivatives Bearing a [2.2]Paracyclophane Skeleton
MS (EI): m/z (%)=299 ([M]+, 76), 194 (100), 180 (13); elemen-
tal analysis calcd for C22H21N: C 88.25, H 7.07, N 4.68; found:
C 87.88, H 7.09, N 4.64.
tramolecular direct arylations of [2.2]paracyclophanes will
now serve as the basis for subsequent studies focusing on
intermolecular variants. Those shall provide a range of
4,5-disubstituted [2.2]paracyclophane derivatives that are
otherwise difficult to prepare. Since many of those are
planar chiral, stereochemical implications and resulting
opportunities will finally be investigated.
4-N-(4’-Methylphenyl)amino[2.2]paracyclophane (5b): The title
compound was prepared according to GP1 using Pd2(dba)3
(56 mg, 0.061 mmol), X-Phos (86 mg, 0.18 mmol), bromide 1b
(574 mg, 2.00 mmol), NaOtBu (269 mg, 2.80 mmol) and 4-meth-
ylaniline (257 mg, 2.40 mmol) in toluene (8 mL) at 758C for
5.5 h. The product was purified by column chromatography (pen-
tane/Et2O=49:1) providing the title compound as a pale orange
solid (489 mg, 78%): m.p. 130–1318C; 1H NMR (300 MHz,
CDCl3): d=7.06–7.00 (m, 3H), 6.88 (d, J=8.4 Hz, 2H), 6.59 (dd,
J=7.8 and 1.7 Hz, 1H), 6.46–6.40 (m, 3H), 6.33 (dd, J=7.7 and
1.5 Hz, 1H), 5.83 (d, J=1.2 Hz, 1H), 5.46 (br s, 1H), 3.12–2.83
(m, 7H), 2.73–2.63 (m, 1H), 2.30 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=141.2, 140.9, 140.9, 139.4, 139.0, 135.8, 133.4, 132.6,
131.2, 130.2, 129.8, 129.6 (2C), 127.4, 126.1, 124.8, 116.8 (2C),
35.2, 35.0, 33.7, 33.7, 20.6; IR (KBr): n˜ =3370, 2922, 2852, 1612,
1590, 1512, 1475, 1412, 1300, 890, 804, 714 cmÀ1; MS (EI): m/z
(%)=313 ([M]+, 84), 312 (54), 209 (89), 208 (100), 194 (44), 193
(49), 104 (21), 91 (12), 78 (10); elemental analysis calcd for
C23H23N: C 88.13 H 7.40, N 4.47; found: C 87.91, H 7.49, N 4.39.
Experimental Section
General Methods
Unless otherwise stated, all starting reagents were commercially
available and used as received. Toluene was freshly distilled with
sodium/benzophenone ketyl radical under nitrogen. NaOtBu was
grinded with a mortar before use. 4-Bromo[2.2]paracyclophane
(1b) was synthesized as described in the literature[19] and purified
by column chromatography (pentane/DCM=9:1). All paracyclo-
phane derivatives are used and prepared as racemates. Reactions
were monitored by thin layer chromatography (TLC) using silica
gel 60 F254 plates and visualized with UV radiation at 254 nm.
Column chromatography was performed using silica gel (Acros,
35–70 mm, 60 ꢀ). Melting points were measured with a Bꢁchi
Melting Point B-540 apparatus. 1H, 13C and 19F NMR were re-
corded either on a Varian Mercury 300, a Varian Inova 400 or
Varian VNMR 600 spectrometer in CDCl3 using TMS as internal
standard. Chemical shifts (d) are reported in ppm and coupling
constants (J) are given in Hz. IR spectra were acquired on a Per-
kinElmer Spectrum FT-IR 100 spectrometer. Mass spectra were
recorded on a Finnigan SSQ 7000 spectrometer. HRMS were re-
corded on a Finnigan MAT 95. Elemental analyses were per-
formed on an Elementar Vario EL instrument.
4-N-(4’-Isopropylphenyl)amino[2.2]paracyclophane (5c): The
title compound was prepared according to GP1 using Pd2(dba)3
(55 mg, 0.060 mmol), X-Phos (86 mg, 0.180 mmol), bromide 1b
(575 mg, 2.00 mmol), NaOtBu (269 mg, 2.80 mmol) and 4-isopro-
pylaniline (326 mg, 2.41 mmol) in toluene (8 mL) at 758C for
4.5 h. Purification by column chromatography (pentane/ethyl
acetate=97:3) provided the title compound as a pale yellow
solid (489 mg, 78%): m.p. 143–1448C; 1H NMR (300 MHz,
CDCl3): d=7.11 (d, J=8.4 Hz, 2H), 7.04 (dd, J=7.8 and 1.5 Hz,
1H), 6.91 (d, J=8.4 Hz, 2H), 6.61 (dd, J=7.9 and 1.7 Hz, 1H),
6.48–6.42 (m, 3H), 6.34 (dd, J=8.1 and 1.5 Hz, 1H), 5.85 (d, J=
1.5 Hz, 1H), 5.48 (br s, 1H), 3.15–2.82 (m, 8H), 2.74–2.65 (m,
1H), 1.26 (d, J=6.9 Hz, 6H); 13C NMR (75 MHz, CDCl3): d=
141.2, 141.1, 140.9, 140.8, 139.4, 139.0, 135.7, 133.4, 132.6, 131.2,
130.3, 127.5, 127.0 (2C), 126.2, 124.9, 116.6 (2C), 35.2, 34.9, 33.7,
33.6, 33.3, 24.1 (2C); IR (KBr): n˜ =3387, 3017, 2955, 2926, 2888,
2855, 1594, 1512, 1478, 1418, 1296, 825, 714 cmÀ1; MS (EI): m/z
(%)=341 ([M]+, 100), 326 (18), 237 (26), 194 (89), 104 (20); ele-
mental analysis calcd for C25H27N: C 87.93, H 7.97, N 4.10;
found: C 87.75, H 8.11, N 4.06.
General Procedure for the N-Arylation: GP1 (Tables 1 and 2)
A Schlenk tube containing a stir bar was dried under vacuum
and charged with Pd2(dba)3 (0.03 equiv), X-Phos (0.09 equiv),
bromide 1b (1–4 mmol), NaOtBu (1.4 equiv) and amine
(1.2 equiv), if solid. The tube was sealed with a rubber septum,
evacuated and backfilled with argon three times. Amine
(1.2 equiv), if liquid, and toluene (0.25m) were added by syringe,
and the septum was replaced by a glass stopper. The solution
was stirred at 758C (preheated oil bath) for 4–6 h, then cooled to
room temperature, diluted with ethyl acetate and filtered over a
pad of Celite. The solvent was removed under reduced pressure
and the product purified by column chromatography.
4-N-(4’-Fluorophenyl)amino[2.2]paracyclophane (5d): The title
compound was prepared according to GP1 using Pd2(dba)3
(55 mg, 0.060 mmol), X-Phos (86 mg, 0.18 mmol), bromide 1b
(575 mg, 2.00 mmol), NaOtBu (270 mg, 2.80 mmol) and 4-fluo-
roaniline (266 mg, 2.40 mmol) in toluene (8 mL) at 758C for 5 h.
The product was purified by column chromatography (pentane/
DCM=7:3) providing the title compound as a white solid
(485 mg, 76%): m.p. 176–1788C; 1H NMR (400 MHz, CDCl3):
d=7.01 (dd, J=7.8 and 2.0 Hz, 1H), 6.97–6.88 (m, 4H), 6.60 (dd,
J=8.0 and 2.0 Hz, 1H), 6.47–6.41 (m, 3H), 6.36 (dd, J=7.8 and
2.0 Hz, 1H), 5.79 (d, J=1.7 Hz, 1H), 5.44 (br s, 1H), 3.10–2.85
(m, 7H), 2.73–2.65 (m, 1H); 13C NMR (100 MHz, CDCl3): d=
157.4 (d, JCF =239 Hz), 141.3, 140.8, 139.7, 139.3, 138.9, 135.8,
133.5, 132.7, 131.2, 130.4, 127.4, 126.5, 125.0, 118.0 (d, JCF =7 Hz)
(2C), 115.6 (d, JCF =23 Hz) (2C), 35.2, 34.9, 33.7, 33.6; 19F NMR
(376 MHz): d=À123.8; IR (KBr): n˜ =3359, 2924, 2851, 1593,
1503, 1413, 1302, 1213, 886, 820, 716 cmÀ1; MS (EI): m/z (%)=
317 ([M]+, 56), 213 (95), 212 (100), 198 (12), 104 (14), 91 (12); el-
emental analysis calcd for C22H20FN: C 83.25, H 6.35, N 4.41;
found: C 83.10, H 6.46, N 4.36.
4-N-(Phenyl)amino[2.2]paracyclophane (5a): The title com-
pound was prepared according to GP1 using Pd2(dba)3 (82 mg,
0.090 mmol), X-Phos (129 mg, 0.270 mmol), bromide 1b (862 mg,
3.00 mmol), NaOtBu (404 mg, 4.20 mmol) and aniline (335 mg,
3.60 mmol) in toluene (12 mL) at 758C for 4.5 h. Purification by
column chromatography (gradient: pentane/Et2O=19:5 to pen-
tane/DCM=7:3) provided the title compound as a white solid
(724 mg, 81%): m.p. 184–1868C; 1H NMR (400 MHz, CDCl3):
d=7.25–7.21 (m, 2H), 7.01 (dd, J=7.7 and 1.7 Hz, 1H), 6.95–
6.92 (m, 2H), 6.90–6.86 (m, 1H), 6.60 (dd, J=8.0 and 1.9 Hz,
1H), 6.48–6.43 (m, 3H), 6.38 (dd, J=9.0 and 1.6 Hz, 1H), 5.87
(d, J=1.9 Hz, 1H), 5.55 (br s, 1H), 3.12–2.87 (m, 7H), 2.73–2.66
(m, 1H); 13C NMR (100 MHz, CDCl3): d=143.5, 141.1, 140.0,
139.4, 138.9, 135.7, 133.4, 132.6, 131.2, 131.1, 129.0 (2C), 127.3,
126.8, 125.8, 120.0, 115.9 (2C), 35.3, 34.9, 33.9, 33.8; IR (KBr):
n˜ =3373, 2925, 2852, 1592, 1565, 1491, 1433, 1306, 1284, 881 cmÀ1
;
Isr. J. Chem. 2012, 52, 171 – 179
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
175

Full Paper
P. Lennartz et al.
4-N-(4’-Trifluoromethylphenyl)amino[2.2]paracyclophane (5e):
The title compound was prepared according to GP1 using
Pd2(dba)3 (55 mg, 0.060 mmol), X-Phos (86 mg, 0.18 mmol), bro-
mide 1b (574 mg, 2.00 mmol), NaOtBu (270 mg, 2.81 mmol) and
4-trifluoromethylaniline (387 mg, 2.40 mmol) in toluene (8 mL)
at 758C for 5 h. Purification by column chromatography (gradi-
ent: pentane/DCM=3:1 to 7:3) provided the title compound as a
(55 mg, 0.060 mmol), X-Phos (86 mg, 0.18 mmol), bromide 1b
(575 mg, 2.00 mmol), NaOtBu (269 mg, 2.80 mmol) and 2-(triiso-
propylsilyloxy)aniline[20] (637 mg, 2.40 mmol) in toluene (8 mL)
at 758C for 4 h. Purification by column chromatography (pen-
tane/ethyl acetate=97:3) provided a mixture of the title com-
pound and X-Phos. The latter compound was removed by a
second column chromatography (pentane/DCM=9:1) to provide
the title compound as a white solid (606 mg, 64%): m.p. 99–
1018C; 1H NMR (300 MHz, CDCl3): d=7.05 (dd, J=7.9 and
1.7 Hz, 1H), 6.88 (dt, J=7.9 and 1.6 Hz, 2H), 6.79 (td, J=7.9
and 1.5 Hz, 1H), 6.70–6.61 (m, 2H), 6.50 (d, J=7.7 Hz, 2H),
6.43–6.38 (m, 2H), 6.15 (br s, 1H), 5.94 (d, J=1.7 Hz, 1H), 3.19–
2.90 (m, 7H), 2.81–2.71 (m, 1H), 1.57–1.42 (m, 3H), 1.28 (d, J=
7.0 Hz, 18H); 13C NMR (75 MHz, CDCl3): d=143.0, 141.1, 139.7,
139.5, 139.0, 135.6, 135.0, 133.5, 132.7, 132.7, 131.3, 127.6, 127.6,
127.1, 121.1, 118.3, 117.3, 112.4, 35.3, 34.9, 33.9, 33.8, 18.2 (6C),
13.1 (3C); IR (KBr): n˜ =3419, 2940, 2863, 1591, 1509, 1441, 1251,
1200, 913, 880, 749 cmÀ1; MS (EI): m/z (%)=471 ([M]+, 100),
428 (18), 367 (42), 238 (11), 193 (16), 104 (18), 59 (15); elemental
analysis calcd for C31H41NOSi: C 78.93, H 8.76, N 2.97; found:
C 78.85, H 8.95, N 2.84.
1
white solid (563 mg, 77%): m.p. 185–1878C; H NMR (300 MHz,
CDCl3): d=7.44 (d, J=8.5 Hz, 2H), 6.95 (dd, J=7.9 and 1.7 Hz,
1H), 6.89 (d, J=8.5 Hz, 2H), 6.61 (dd, J=7.9 and 1.7 Hz, 1H),
6.53–6.44 (m, 4H), 5.90 (d, J=1.5 Hz, 1H), 5.74 (br s, 1H), 3.11–
2.88 (m, 7H), 2.77–2.67 (m, 1H); 13C NMR (75 MHz, CDCl3):
d=146.9, 141.5, 139.5, 139.1, 138.3, 136.0, 133.7, 133.3, 132.9,
131.2, 128.8, 127.7, 127.3, 126.5 (q, JCF =4 Hz) (2C), 121.1 (q,
J
CF =33 Hz), 114.1 (2C), 35.2, 34.8, 34.0, 33.8, CF3 was not ob-
served; 19F NMR (282 MHz): d=À61.3; IR (KBr): n˜ =3364,
2929, 2852, 1616, 1523, 1483, 1322, 1284, 1103, 1063, 827 cmÀ1
;
MS (EI): m/z (%)=367 ([M]+, 65), 263 (100), 262 (98), 248 (10),
194 (30), 193 (38), 104 (25), 78 (10); elemental analysis calcd for
C23H20F3N: C 75.19, H 5.49, N 3.81; found: C 75.26, H 5.52,
N 3.59.
4-(N-Methyl-N-phenyl)amino[2.2]paracyclophane (7a):[25] Under
an argon atmosphere 5a (299 mg, 1.00 mmol) was dissolved in
DMF (5 mL), and NaH (125 mg, 3.13 mmol) was added in small
portions at 08C. The solution was warmed to room temperature
and stirred for 2 h. MeI (444 mg, 3.13 mmol) was slowly added
and the solution was stirred over night. Water (20 mL) was
added and the product was extracted with ethyl acetate (3ꢂ
25 mL), dried over Na2SO4 and the solvent removed in vacuo.
Purification by column chromatography (pentane/ethyl acetate=
19:1) provided the title compound as a white solid (256 mg,
82%): m.p. 142–1438C; 1H NMR (300 MHz, CDCl3): d=7.24–
7.18 (m, 2H), 7.01–6.98 (m, 2H), 6.90 (tt, J=7.4 and 1.2 Hz,
1H), 6.78 (dd, J=7.8 and 2.0 Hz, 1H), 6.60 (dd, J=7.8 and
1.7 Hz, 1H), 6.51 (dd, J=7.9 and 1.7 Hz, 2H), 6.38–6.31 (m,
2H), 6.01 (d, J=1.5 Hz, 1H), 3.42 (s, 3H), 3.13–2.87 (m, 6H),
2.69–2.60 (m, 1H), 2.54–2.44 (m, 1H); 13C NMR (75 MHz,
CDCl3): d=150.7, 145.6, 140.9, 140.1, 138.8, 136.2, 133.6, 132.9,
132.8, 131.1, 129.4, 129.0 (2C), 127.5, 123.8, 121.0, 119.4 (2C),
40.6, 35.4, 35.3, 34.9, 34.5; IR (KBr): n˜ =1702, 1596, 1479, 1340,
1283, 1113, 1054, 835, 749 cmÀ1; MS (EI): m/z (%)=313 ([M]+,
100), 208 (69), 194 (20), 104 (24), 78 (14); elemental analysis
calcd for C23H23N: C 88.13, H 7.40, N 4.47; found: C 87.88,
H 7.30, N 4.34.
4-N-(3’-Methylphenyl)amino[2.2]paracyclophane (5 f): The title
compound was prepared according to GP1 using Pd2(dba)3
(55 mg, 0.060 mmol), X-Phos (86 mg, 0.18 mmol), bromide 1b
(575 mg, 2.00 mmol), NaOtBu (271 mg, 2.82 mmol) and 3-meth-
ylaniline (257 mg, 2.40 mmol) in toluene (8 mL) at 758C for
6.5 h. Purification by column chromatography (gradient: pen-
tane/Et2O=97:3 to pentane/DCM=7:3) provided the title com-
pound as a pale yellow solid (354 mg, 57%): m.p. 169–1718C;
1H NMR (300 MHz, CDCl3): d=7.17–7.11 (m, 1H), 7.03 (dd, J=
7.9 and 2.0 Hz, 1H), 6.78–6.71 (m, 3H), 6.62 (dd, J=7.9 and
2.0 Hz, 1H), 6.50–6.37 (m, 4H), 5.87 (d, J=1.7 Hz, 1H), 5.52 (br
s, 1H), 3.16–2.89 (m, 7H), 2.76–2.66 (m, 1H), 2.33 (s, 3H);
13C NMR (75 MHz, CDCl3): d=143.5, 141.1, 140.2, 139.5, 138.9,
138.9, 135.8, 133.5, 132.7, 131.3, 131.2, 128.9, 127.4, 126.7, 125.8,
120.9, 116.7, 113.0, 35.2, 34.8, 33.8, 33.7, 21.5; IR (KBr): n˜ =3369,
2925, 2855, 1591, 1477, 1303, 1161, 873, 768, 703 cmÀ1; MS (EI):
m/z (%)=313 ([M]+, 100), 208 (91), 193 (37), 104 (19), 91 (11),
78 (10); elemental analysis calcd for C23H23N: C 88.13, H 7.40,
N 4.47; found: C 87.86, H 7.70, N 4.34.
4-N-(2’-methoxycarbonylphenyl)amino[2.2]paracyclophane (5g):
The title compound was prepared according to GP1 using
Pd2(dba)3 (54 mg, 0.059 mmol), X-Phos (86 mg, 0.18 mmol), bro-
mide 1b (574 mg, 2.00 mmol), NaOtBu (269 mg, 2.80 mmol) and
methyl anthranilate (362 mg, 2.39 mmol) in toluene (8 mL) at
758C for 5 h. The product was purified by column chromatogra-
phy (pentane/ethyl acetate=19:1) providing the title compound
as a yellow solid (621 mg, 87%): m.p. 159–1618C; 1H NMR
(400 MHz, CDCl3): d=9.42 (br s, 1H), 8.00 (dd, J=8.0 and
1.7 Hz, 1H), 7.23 (ddd, J=8.3, 7.0 and 2.0 Hz, 1H), 7.14 (dd, J=
8.3 and 1.7 Hz, 1H), 6.91 (d, J=8.1 Hz, 1H), 6.69 (ddd, J=8.1,
7.0 and 1.0 Hz, 1H), 6.59–6.45 (m, 5H), 6.08 (d, J=1.7 Hz, 1H),
4.01 (s, 3H), 3.15–2.92 (m, 7H), 2.74–2.67 (m, 1H); 13C NMR
(75 MHz, CDCl3): d=169.2, 147.7, 141.3, 139.6, 139.0, 138.5,
135.6, 134.3, 134.2, 133.5, 132.8, 131.6, 131.4, 129.8, 128.6, 127.8,
116.5, 113.4, 110.6, 51.8, 35.2, 34.8, 33.8, 33.7; IR (KBr): n˜ =3309,
2931, 1674, 1588, 1513, 1491, 1449, 1233, 1086, 749 cmÀ1; MS
(EI): m/z (%)=357 ([M]+, 64), 253 (78), 221 (51), 194 (83), 193
(100), 165 (15), 104 (52), 78 (19), 59 (10); elemental analysis
calcd for C24H23NO2: C 80.64, H 6.49, N 3.92; found: C 80.27,
H 6.69, N 3.86.
General Procedure for the Oxidative Cyclization: GP2 (Tables 4
and 5)
A 10 mL Schlenk tube equipped with a reflux condenser, and a
stir bar was dried under vacuum. The tube was charged with
Pd(OAc)2 (0.20 equiv), PivOH (0.6 equiv) and AcOH (2 mL).
The solution was stirred for 5 min. Aryl [2.2]paracyclophanyl
amines 5a–h (0.4 mmol) and AcOH (2 mL) were added to the
yellow solution. Dry air was introduced into the solution with a
Teflon tube, and the solution was stirred at 1208C. After approxi-
mately 15–30 min the solution turned black. After 8 h the solu-
tion was cooled to room temperature, diluted with ethyl acetate
(50 mL), washed with NaHCO3 (50 mL) and water (50 mL),
dried over MgSO4, and the solvent was removed under reduced
pressure. The residue was purified by column chromatography.
[2]Paracyclo[2](1,4)carbazolophane (2a): The title compound
was prepared according to GP2 using Pd(OAc)2 (18 mg,
0.080 mmol), PivOH (25 mg, 0.24 mmol) and amine 5a (120 mg,
4-N-(2’-triisoproylsilyloxy)amino[2.2]paracyclophane (5h): The
title compound was prepared according to GP1 using Pd2(dba)3
176
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2012, 52, 171 – 179

Synthesis of Planar Chiral Carbazole Derivatives Bearing a [2.2]Paracyclophane Skeleton
0.401 mmol) in AcOH (4 mL) for 8 h. Purification by column
1H), 6.52 (dd, J=7.9 and 2.0 Hz, 1H), 6.37 (dd, J=7.9 and
chromatography (pentane/Et2O=9:1) provided the title com-
pound as a white solid (75 mg, 62%): m.p. 239–2418C; H NMR
2.0 Hz, 1H), 5.94 (dd, J=7.7 and 2.0 Hz, 1H), 5.29 (dd, J=7.7
and 2.0 Hz, 1H), 3.95–3.88 (m, 1H), 3.37–3.26 (m, 1H), 3.19–2.91
(m, 6H); 13C NMR (75 MHz, CDCl3): d=157.6 (d, JCF =233 Hz),
141.1, 137.8, 137.3, 135.8, 135.1 (2C), 132.1, 131.5, 126.4, 126.3,
125.4 (d, JCF =10 Hz), 125.2 (d, JCF =5 Hz), 124.5, 122.4, 112.7 (d,
1
(400 MHz, CDCl3): d=8.06 (d, J=8.0 Hz, 1H), 7.87 (br s, 1H),
7.46 (d, J=8.0 Hz, 1H), 7.40 (dt, J=7.6 and 1.1 Hz, 1H), 7.28–
7.24 (m, 1H), 6.63 (d, J=7.4 Hz, 1H), 6.56 (d, J=7.4 Hz, 1H),
6.50 (dd, J=7.9 and 1.9 Hz, 1H), 6.36 (dd, J=7.7 and 1.9 Hz,
1H), 5.94 (dd, J=7.7 and 1.9 Hz, 1H), 5.23 (dd, J=7.7 and
1.9 Hz, 1H), 4.03–3.98 (m, 1H), 3.40–3.31 (m, 1H), 3.16–2.91 (m,
6H); 13C NMR (75 MHz, CDCl3): d=140.0, 138.8, 137.9, 137.3,
135.7, 132.0, 131.5, 131.0, 126.4, 126.3, 125.4, 125.3, 124.8, 124.5,
122.4, 122.2, 119.6, 110.6, 33.9, 33.7, 33.2, 31.1; IR (ATR): n˜ =
3392, 2924, 1592, 1572, 1499, 1456, 1394, 1322, 1299, 1247, 1026,
905, 871, 805, 747 cmÀ1; MS (EI): m/z (%)=297 ([M]+, 39), 193
(100), 192 (11), 165 (4), 149 (4), 104 (2); HRMS (EI) calcd for
C22H19N: 297.1512; found: 297.1510 [M]+.
J
CF =26 Hz), 111.1 (d, JCF =10 Hz), 107.7 (d, JCF =24 Hz), 33.8,
33.5, 33.2, 31.0; 19F NMR (282 MHz): d=À124.2; IR (ATR): n˜ =
3397, 2925, 1581, 1477, 1388, 1309, 1275, 1247, 1176, 1021, 961,
909, 862, 803, 731 cmÀ1; MS (EI): m/z (%)=315 ([M]+, 37), 211
(100), 210 (12), 183 (5), 157 (5), 104 (9); HRMS (ESI) calcd for
C22H19FN: 316.1496; found: 316.1498 [M+H]+.
[2]Paracyclo[2]6-trifluoromethyl(1,4)carbazolophane (2e): The
title compound was prepared according to GP2 using Pd(OAc)2
(18 mg, 0.080 mmol), PivOH (25 mg, 0.24 mmol) and amine 5e
(147 mg, 0.400 mmol) in AcOH (4 mL) for 8 h. The product was
purified by column chromatography (gradient pentane/Et2O=
4:1 to 7:3) providing the title compound as a light yellow solid
[2]Paracyclo[2]6-methyl(1,4)carbazolophane (2b): The title com-
pound was prepared according to GP2 using Pd(OAc)2 (18 mg,
0.080 mmol), PivOH (25 mg, 0.24 mmol) and amine 5b (126 mg,
0.402 mmol) in AcOH (4 mL) for 8 h. The product was purified
by column chromatography (pentane/Et2O=9:1) providing the
title compound as a light yellow solid (47 mg, 38%): m.p. 208–
1
(32 mg, 22%): m.p. 189–1918C; H NMR (600 MHz, CDCl3): d=
8.32 (s, 1H), 8.03 (br s, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.52 (d, J=
8.9 Hz, 1H), 6.70 (d, J=7.4 Hz, 1H), 6.64 (d, J=7.4 Hz, 1H),
6.53 (dd, J=7.7 and 1.8 Hz, 1H), 6.39 (dd, J=7.7 and 1.8 Hz,
1H), 5.92 (dd, J=7.7 and 1.8 Hz, 1H), 5.22 (dd, J=7.7 and
2.0 Hz, 1H), 4.02–3.98 (m, 1H), 3.36–3.30 (m, 1H), 3.20–3.00 (m,
5H), 2.96–2.91 (m 1H); 13C NMR (150 MHz, CDCl3): d=140.6,
140.2, 137.8, 137.3, 136.0, 132.2, 131.9, 131.7, 127.3, 126.3, 125.4
(q, JCF =271 Hz), 125.0, 124.7, 124.6, 122.5, 121.9 (q, JCF =32 Hz)
121.9 (q, JCF =3 Hz), 119.7 (q, JCF =5 Hz), 110.7, 33.8, 33.6, 33.1,
31.0; 19F (564 MHz): d=À59.9; IR (ATR): n˜ =3390, 2929, 1623,
1
2108C; H NMR (300 MHz, CDCl3): d=7.86 (d, J=0.5 Hz, 1H),
7.75 (br s, 1H), 7.35 (d, J=8.2 Hz, 1H), 7.23 (dm, J=8.2 Hz,
1H), 6.61 (d, J=7.4 Hz, 1H), 6.56–6.50 (m, 2H), 6.37 (dd, J=7.8
and 1.9 Hz, 1H), 5.96 (dd, J=7.7 and 2.0 Hz, 1H), 5.29 (dd, J=
7.7 and 1.9 Hz, 1H), 4.05–3.98 (m, 1H), 3.38–3.26 (m, 1H), 3.17–
2.93 (m, 6H), 2.58 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
140.3, 137.9, 137.3, 137.0, 135.7, 131.9, 131.4, 130.8, 128.8, 126.3,
126.2, 126.1, 125.4, 125.2, 124.5, 122.2, 122.1, 110.2, 33.9, 33.7,
33.2, 31.0, 21.3; IR (ATR): n˜ =3399, 2923, 2855, 1591, 1500, 1470,
1437, 1389, 1308, 1246, 1184, 905, 873, 797, 725 cmÀ1; MS (EI):
m/z (%)=311 ([M]+, 40), 207 (100), 206 (17), 204 (6), 191 (6),
104 (7); HRMS (ESI) calcd for C23H22N: 312.1747; found:
312.1753 [M+H]+.
1588, 1391, 1323, 1261, 1163, 1109, 1070, 886, 808, 716 cmÀ1
;
MS(EI): m/z (%)=365 ([M]+, 60), 261 (100), 191 (10), 104 (18),
78 (6); HRMS (ESI) calcd for C23H19NF3: 366.1464; found:
366.1464 [M+H]+.
[2]Paracyclo[2]7-methyl(1,4)carbazolophane (2 f): The title com-
pound was prepared according to GP2 using Pd(OAc)2 (18 mg,
0.080 mmol), PivOH (25 mg, 0.24 mmol) and amine 5 f (125 mg,
0.399 mmol) in AcOH (4 mL) for 8 h. Purification by column
[2]Paracyclo[2]6-isopropyl(1,4)carbazolophane (2c): The title
compound was prepared according to GP2 using Pd(OAc)2
(18 mg, 0.080 mmol), PivOH (25 mg, 0.24 mmol) and amine 5c
(137 mg, 0.401 mmol) in AcOH (4 mL) for 8 h. Purification by
column chromatography (gradient pentane/Et2O=9:1 to 17:3 to
4:1) provided the title compound as a white solid (51 mg, 37%):
m.p. 128–1308C; 1H NMR (300 MHz, CDCl3): d=7.92 (s, 1H),
7.74 (br s, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.31 (dd, J=8.2 and
1.7 Hz, 1H), 6.63 (d, J=7.4 Hz, 1H), 6.57 (d, J=7.4 Hz, 1H),
6.53 (dd, J=7.9 and 2.0 Hz, 1H), 6.37 (dd, J=7.9 and 2.0 Hz,
1H), 5.95 (dd, J=7.7 and 2.0 Hz, 1H), 5.24 (dd, J=7.7 and
2.0 Hz, 1H), 4.09–4.02 (m, 1H), 3.37–2.91 (m, 8H), 1.43 (d, J=
6.9 Hz, 6H); 13C NMR (75 MHz, CDCl3): d=140.3, 140.3, 137.8,
137.3, 137.2, 135.5, 131.9, 131.3, 130.6, 126.2, 126.2, 125.4, 125.3,
124.4, 123.6, 122.1, 119.6, 110.3, 34.3, 33.9, 33.8, 33.2, 31.0, 24.9,
24.8; IR (ATR): n˜ =3396, 2954, 2928, 2861, 1591, 1501, 1470,
1388, 1317, 1245, 907, 876, 803, 725 cmÀ1; MS (EI): m/z (%)=
339 ([M]+, 57), 235 (100), 220 (40), 204 (11), 104 (13); HRMS
(ESI) calcd for C25H26N: 340.2060; found: 340.2064 [M+H]+.
chromatography (pentane/Et2O=9:1) followed by
a second
column chromatography (pentane/CHCl3 =3:7) provided the
title compound as a white solid (37 mg, 30%): m.p. 206–2098C;
1H NMR (300 MHz, CDCl3): d=7.93 (d, J=7.9 Hz, 1H), 7.72
(br, 1H), 7.23 (s, 1H), 7.09 (d, J=7.6 Hz, 1H), 6.60 (d, J=
7.7 Hz, 1H), 6.54 (d, J=7.7 Hz, 1H), 6.50 (dd, J=7.9 and 2.0 Hz,
1H), 6.37 (dd, J=7.9 and 2.0 Hz, 1H), 5.95 (dd, J=7.7 and
2.0 Hz, 1H), 5.28 (dd, J=7.7 and 2.0 Hz, 1H), 4.01–3.94 (m,
1H), 3.38–3.26 (m, 1H), 3.16–2.90 (m, 6H), 2.56 (s, 3H);
13C NMR (75 MHz, CDCl3): d=139.9, 139.3, 137.9, 137.2, 135.3,
134.9, 131.9, 131.4, 130.4, 126.3, 126.2, 125.5, 124.5, 123.1, 122.0,
122.0, 121.2, 110.7, 33.9, 33.6, 33.2, 31.1, 22.0; IR (ATR): n˜ =
3400, 3028, 2924, 2856, 1734, 1625, 1594, 1500, 1444, 1399, 1317,
1249, 1022, 926, 857, 800 cmÀ1; MS(EI): m/z (%)=311 ([M]+,
71), 207 (100), 206 (25), 191 (6), 104 (11); HRMS (EI) calcd for
C23H21N: 311.1669; found: 311.1668 [M]+.
[2]Paracyclo[2]8-methoxycarbonyl(1,4)carbazolophane (2g): The
title compound was prepared according to GP2 using Pd(OAc)2
(18 mg, 0.080 mmol), PivOH (25 mg, 0.24 mmol) and amine 5g
(143 mg, 0.400 mmol) in AcOH (4 mL) for 8 h. Purification by
column chromatography (pentane/Et2O=9:1) provided the title
compound as a light yellow solid (83 mg, 58%): m.p. 207–2098C;
1H NMR (300 MHz, CDCl3): d=9.88 (br s, 1H), 8.27 (d, J=
7.7 Hz, 1H), 8.09 (dd, J=7.7 and 1.2 Hz, 1H), 7.30 (t, J=7.8 Hz,
1H), 6.71 (d, J=7.7 Hz, 1H), 6.63 (d, J=7.7 Hz, 1H), 6.52 (dd,
J=7.8 and 1.9 Hz, 1H), 6.39 (dd, J=7.8 and 1.9 Hz, 1H), 5.96
[2]Paracyclo[2]6-fluoro(1,4)carbazolophane (2d): The title com-
pound was prepared according to GP2 using Pd(OAc)2 (18 mg,
0.080 mmol), PivOH (25 mg, 0.24 mmol) and amine 5d (127 mg,
0.400 mmol) in AcOH (4 mL) for 8 h. Purification by column
chromatography (gradient pentane/Et2O=9:1 to 4:1) provided
the title compound as a light yellow solid (44 mg, 35%): m.p.
181–1848C; H NMR (300 MHz, CDCl3): d=7.80 (br s, 1H), 7.73
(dd, J=9.7 and 2.5 Hz, 1H), 7.39–7.35 (m, 1H), 7.16 (td, J=9.0
and 2.5 Hz, 1H), 6.65 (d, J=7.4 Hz, 1H), 6.57 (d, J=7.4 Hz,
1
Isr. J. Chem. 2012, 52, 171 – 179
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177

Full Paper
P. Lennartz et al.
(dd, J=7.7 and 2.0 Hz, 1H), 5.19 (dd, J=7.7 and 2.0 Hz, 1H),
4.08 (s, 3H), 4.03–3.96 (m, 1H), 3.52–3.41 (m, 1H), 3.20–3.05 (m,
5H), 2.97–2.89 (m, 1H); 13C NMR (75 MHz, CDCl3): d=168.2,
140.4, 139.5, 137.5 (2C), 135.7, 132.1, 131.6, 131.5, 127.6, 126.9,
126.5, 126.3, 126.0, 124.6, 124.5, 122.8, 118.6, 111.3, 51.9, 33.8,
33.6, 33.0, 31.0; IR (ATR): n˜ =3419, 2939, 1695, 1592, 1502, 1434,
1392, 1293, 1266, 1236, 1195, 1145, 867, 800, 743, 714 cmÀ1; MS
(EI): m/z (%)=355 ([M]+, 53), 251 (100), 219 (48), 190 (21), 164
(16), 104 (15); HRMS (ESI) calcd for C24H22NO2: 356.1645;
found: 356.1643 [M+H]+.
bridge CB12 1EZ, United Kingdom (Fax: 44-1223-336033 or
email: deposit@ccdc.cam.ac.uk).
Acknowledgements
This work was partly supported by the Deutsche For-
schungsgemeinschaft (IRTG 1628) and the Fonds der
Chemischen Industrie, Germany.
[2]Paracyclo[2]8-triisopropylsilyloxy(1,4)carbazolophane
(2h):
The title compound was prepared according to GP2 using
Pd(OAc)2 (18 mg, 0.080 mmol), PivOH (25 mg, 0.24 mmol) and
amine 5h (189 mg, 0.401 mmol) in AcOH (4 mL) for 7.5 h. Pu-
rification by column chromatography (gradient pentane/Et2O=
49:1 to 19:1) provided the title compound as a light yellow solid
(111 mg, 59%): m.p. 125–1298C; 1H NMR (300 MHz, CDCl3):
d=7.90 (br s, 1H), 7.69 (d, J=8.2 Hz, 1H), 7.12 (t, J=7.8 Hz,
1H), 6.93 (dd, J=7.7 and 0.7 Hz, 1H), 6.64 (d, J=7.4 Hz, 1H),
6.57 (d, J=7.4 Hz, 1H), 6.52 (dd, J=7.9 and 1.7 Hz, 1H), 6.38
(dd, J=7.7 and 2.0 Hz, 1H), 5.99 (dd, J=7.7 and 2.0 Hz, 1H),
5.27 (dd, J=7.7 and 1.9 Hz, 1H), 4.05–3.96 (m, 1H), 3.40–3.31
(m, 1H), 3.17–2.91 (m, 6H), 1.54–1.42 (m, 3H), 1.25 (dd, J=7.4
and 3.0 Hz, 18H); 13C NMR (75 MHz, CDCl3): d=141.5, 139.6,
137.9, 137.2, 135.8, 131.9, 131.4, 131.4, 130.8, 126.7, 126.3, 126.2,
126.1, 124.4, 122.4, 120.0, 115.3, 113.1, 34.0, 33.6, 33.2, 31.1, 18.1
(6C), 12.9 (3C); IR (ATR): n˜ =3430, 2939, 2862, 1620, 1572,
1495, 1458, 1391, 1306, 1260, 1106, 1061, 1006, 974, 879, 785,
726 cmÀ1; MS (EI): m/z (%)=469 ([M]+, 44), 365 (100), 322
(11), 252 (8), 236 (12), 104 (13); HRMS (ESI) calcd for
C31H40ONSi: 470.2874; found: 470.2868 [M+H]+.
References
[1] a) D. J. Cram, H. Steinberg, J. Am. Chem. Soc. 1951, 73,
5691–5704; b) for the initial discovery, see: C. J. Brown,
A. C. Farthing, Nature 1949, 164, 915–916.
[2] Modern Cyclophane Chemistry, (Eds: R. Gleiter, H. Hopf)
Wiley-VCH, New York, 2004.
[3] H. Hopf, Naturwiss. 1983, 70, 349–358.
[4] a) S. E. Gibson, J. D. Knight, Org. Biomol. Chem. 2003, 1,
1256–1269; b) V. Rozenberg, E. Sergeeva, H. Hopf, in Ref.
[2], pp. 453–462; c) S. Brꢃse, S. Dahmen, S. Hçfener, F. Lau-
terwasser, M. Kreis, R. E. Ziegert, Synlett 2004, 2647–2669.
[5] A. A. Aly, A. B. Brown, Tetrahedron 2009, 65, 8055–8089.
[6] For examples of fused heterocyclic [2.2]paracyclophanes,
see: a) U. Wçrsdçrfer, F. Vçgtle, F. Glorius, A. Pfalz, J.
Prakt. Chem. 1999, 341, 445–448; b) F. Fringuelli, O. Pier-
matti, F. Pizzo, R. Ruzziconi, Chem. Lett. 2000, 38–39; c) B.
Ortner, R. Waibel, P. Gmeiner, Angew. Chem. 2001, 113,
1323–1325; Angew. Chem. Int. Ed. 2001, 40, 1283–1285;
d) B. Ortner, H. Hꢁbner, P. Gmeiner, Tetrahedron: Asym-
metry 2001, 12, 3205–3208; e) V. Rozenberg, T. Danilova,
E. Sergeeva, E. Vorontsov, Z. Starikova, A. Korlyukov, H.
Hopf, Eur. J. Org. Chem. 2002, 468–477; f) A. Cipiciani, F.
Fringuelli, O. Piermatti, F. Pizzo, R. Ruzziconi, J. Org.
Chem. 2002, 67, 2665–2670; g) L. Minuti, A. Marrocchi, I.
Tesei, E. Gacs-Baitz, Tetrahedron Lett. 2005, 46, 8789–8792;
h) P. B. Hitchcock, A. C. C. Hodgson, G. J. Rowlands, Syn-
lett 2006, 2625–2628; i) N. De Rycke, J. Marrot, F. Couty,
O. R. P. David, Eur. J. Org. Chem. 2011, 1980–1984.
[7] a) H. Hopf, D. G. Barrett, Liebigs Ann. 1995, 449–451;
b) A. Cipiciani, F. Fringuelli, V. Mancini, O. Piermatti, F.
Pizzo, J. Org. Chem. 1997, 62, 3744–3747; c) V. Rozenberg,
T. Danilova, E. Sergeeva, E. Vorontsov, Z. Starikova, K. Ly-
senko, Y. Belokon, Eur. J. Org. Chem. 2000, 3295–3303;
d) T. Focken, H. Hopf, V. Snieckus, I. Dix, P. G. Jones, Eur.
J. Org. Chem. 2001, 2221–2228; e) V. I. Rozenberg, T. I.
Danilova, E. V. Sergeeva, I. A. Shouklov, Z. A. Starikova,
H. Hopf, K. Kꢁhlein, Eur. J. Org. Chem. 2003, 432–440;
f) C. Bolm, D. K. Whelligan, Adv. Synth. Catal. 2006, 348,
2093–2100; g) D. K. Whelligan, C. Bolm, J. Org. Chem.
2006, 71, 4609–4618; h) N. Hermanns, S. Dahmen, C. Bolm,
S. Brꢃse, Angew. Chem. 2002, 114, 3844–3846; Angew.
Chem. Int. Ed. 2002, 41, 3692–3694; i) V. Rozenberg, R.
Zhuravsky, E. Sergeeva, Chirality 2006, 18, 95–102.
Crystal structure analysis of racemic 2a: Crystals of 2a suitable
for X-ray structure determination were obtained from a ben-
zene/pentane mixture at room temperature. The compound crys-
¯
tallizes in the centrosymmetric trigonal space group R3 (148,
hexagonal axes) with cell constants a=b=22.6870(6), c=
17.5427(5) ꢀ, and cell volume of V=7819.5(5) ꢀ3. Z=18 and a
molecular weight of 328.45 (vide infra) result in a calculated den-
sity of 1calcd =1.255 MgmÀ3 and an absorption coefficient of m=
0.547 mmÀ1 (CuKa radiation, l=1.54178 ꢀ) A total number of
40818 data were collected at ambient temperature on a Bruker
APEX DUO CCD diffractometer. The structure was solved em-
ploying direct methods as implemented in the SHELXTL pro-
gram package.[26] The data set was merged (req =0.032) to give
2667 reflections with I>2s(I), which were included into the final
full-matrix least-squares refinement on F employing XTAL3.7.[27]
The refinement converged at r=0.076 (rw =0.090), a goodness of
fit S=1.430, a final maximum shift/error of 0.26·10À3, and a resid-
ual electron density of À0.87/+0.59e. All but two (vide infra)
non-hydrogen atoms were refined anisotropically. The hydrogen
atoms were calculated in idealized positions and their U values
were fixed at 1.5 times the Ueq of the relevant heavy atom prior
to final refinement. No refinement of hydrogen parameters. The
compound crystallizes together with one molecule of benzene
and a probably non-stoichiometric amount of severely disordered
pentane. While the benzene unit could be refined as described
above, this was not possible for the pentane unit. Thus the corre-
sponding density was absorbed by two carbon and two hydrogen
atoms, where the carbon parameters could be refined isotropical-
ly. Additional crystallographic data for the structure of 2a have
been deposited with the Cambridge Crystallographic Data
Centre (CCDC-832923). Copies can be obtained, free of charge,
on application to the Director, CCDC, 12 Union Road, Cam-
[8] For tert-butylsulfinyl as directing group, see: P. B. Hitchcock,
G. J. Rowlands, R. J. Seacome, Org. Biomol. Chem. 2005, 3,
3873–3876.
[9] a) X.-L. Hou, X.-W. Wu, L.-X. Dai, B.-X. Cao, J. Sun,
Chem. Commun. 2000, 1195–1196; b) A. Pelter, B. Mootoo,
A. Maxwell, A. Reid, Tetrahedron Lett. 2001, 42, 8391–
8394; c) C. Bolm, K. Wenz, G. Raabe, J. Organomet. Chem.
178
www.ijc.wiley-vch.de
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2012, 52, 171 – 179

Synthesis of Planar Chiral Carbazole Derivatives Bearing a [2.2]Paracyclophane Skeleton
2002, 662, 23–33; d) G. J. Rowlands, Org. Biomol. Chem.
2008, 6, 1527–1534.
Deprez, L. V. Desai, M. S. Sanford, J. Am. Chem. Soc. 2005,
127, 7330–7331; c) O. Daugulis, V. G. Zaitsev, Angew.
Chem. 2005, 117, 4114–4116; Angew. Chem. Int. Ed. 2005,
44, 4046–4048; d) S. Yang, B. Li, X. Wan, Z. Shi, J. Am.
Chem. Soc. 2007, 129, 6066–6067; e) D. Shabashov, O. Dau-
gulis, J. Org. Chem. 2007, 72, 7720–7725.
[10] For selected reviews about direct arylation see: a) L.-C.
Campeau, K. Fagnou, Chem. Commun. 2006, 1253–1264;
b) D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007,
107, 174–238; c) X. Chen, K. M. Engle, D.-H. Wang, J.-Q.
Yu, Angew. Chem. 2009, 121, 5196–5217; Angew. Chem. Int.
Ed. 2009, 48, 5094–5115; d) G. P. McGlacken, L. M. Bate-
man, Chem. Soc. Rev. 2009, 38, 2447–2464; e) O. Daugulis,
Top. Curr. Chem. 2010, 292, 57–84; f) C.-L. Sun, B.-J. Li, Z.-
J. Shi, Chem. Commun. 2010, 46, 677–685; g) T. W. Lyons,
M. S. Sanford, Chem. Rev. 2010, 110, 1147–1169; h) C. Liu,
H. Zhang, W. Shi, A. Lei, Chem. Rev. 2011, 111, 1780–1824.
[11] a) H.-J. Knçlker, K. R. Reddy, Chem. Rev. 2002, 102, 4303–
4428; b) H.-J. Knçlker, Top. Curr. Chem. 2005, 244, 115–
148; c) S.-L. You, J.-B. Xia, Top. Curr. Chem. 2010, 292,
165–194.
[17] a) A. R. Muci, S. L. Buchwald, Top. Curr. Chem. 2002, 219,
131–209; b) J. F. Hartwig, Synlett 2006, 1283–1294.
[18] a) K. Rossen, P. J. Pye, A. Maliakal, R. P. Volante, J. Org.
Chem. 1997, 62, 6462–6463; b) M. Kreis, C. J. Friedmann, S.
Brꢃse, Chem. Eur. J. 2005, 11, 7387–7394; c) M. Kreis, M.
Nieger, S. Brꢃse, J. Organomet. Chem. 2006, 691, 2171–
2181; d) B. Qu, Y. Ma, Q. Ma, X. Liu, F. He, C. Song, J.
Org. Chem. 2009, 74, 6867–6869.
[19] D. J. Cram, A. C. Day, J. Org. Chem. 1966, 31, 1227–1232.
[20] Y. Kondo, S. Kojima, T. Sakamoto, J. Org. Chem. 1997, 62,
6507–6511.
[12] a) C. Bolm, T. Focken, G. Raabe, Tetrahedron: Asymmetry
2003, 14, 1733–1746; b) T. Focken, G. Raabe, C. Bolm, Tet-
rahedron: Asymmetry 2004, 15, 1693–1706; c) T. Focken, J.
Rudolph, C. Bolm, Synthesis 2005, 429–436.
[13] H. Hopf, Angew. Chem. 2008, 120, 9954–9958; Angew.
Chem. Int. Ed. 2008, 47, 9808–9812.
[21] For precedent syntheses of carbazoles reported in the litera-
ture, substoichiometric or stoichiometric amounts of
Pd(OAc)2 have been used. For examples, see Ref. [11c].
[22] For examples of additive effects in metal-catalyzed CÀH ac-
tivations, see: a) M. Lafrance, K. Fagnou, J. Am. Chem. Soc.
2006, 128, 16496–16497; b) O. Renꢄ, K. Fagnou, Adv. Synth.
Catal. 2010, 352, 2116–2120; c) C.-L. Sun, H. Li, D.-G. Yu,
M. Yu, X. Zhou, X.-Y. Lu, K. Huang, S.-F. Zheng, B.-J. Li,
Z.-J. Shi, Nat. Chem. 2010, 2, 1044–1049.
[23] For the beneficial effect of TFBA, see: K.-S. Masters,
T. R. M. Rauws, A. K. Yadav, W. A. Herrebout, B. Van der
Veken, B. U. W. Maes, Chem. Eur. J. 2011, 17, 6315–6320.
[24] For examples with similar regioselectivity, see: R. Forke, A.
Jꢃger, H.-J. Knçlker, Org. Biomol. Chem. 2008, 6, 2481–
2483.
[25] For a similar N-methylation, see: W. Bi, X. Yun, Y. Fan, X.
Qi, Y. Du, J. Huang, Synlett 2010, 2899–2904.
[26] a) G. M. Sheldrick, Acta Crystallogr. 2008, A64, 112–122;
b) Version 6.10. Bruker AXS Inc. Madison, Wisconsin,
USA.
[27] S. R. Hall, D. J. du Boulay, R. Olthof-Hazekamp, Eds.,
2000, Xtal3.7 System. University of Western Australia.
[14] a) W. C. P. Tsang, N. Zheng, S. L. Buchwald, J. Am. Chem.
Soc. 2005, 127, 14560–14561; b) W. C. P. Tsang, R. H.
Munday, G. Brasche, N. Zheng, S. L. Buchwald, J. Org.
Chem. 2008, 73, 7603–7610; c) J. A. Jordan-Hore, C. C. C.
Johansson, M. Gulias, E. M. Beck, M. J. Gaunt, J. Am.
Chem. Soc. 2008, 130, 16184–16186; d) B.-J. Li, S.-L. Tian,
Z. Fang, Z.-J. Shi, Angew. Chem. 2008, 120, 1131–1134;
Angew. Chem. Int. Ed. 2008, 47, 1115–1118; e) S. H. Cho, J.
Yoon, S. Chang, J. Am. Chem. Soc. 2011, 133, 5996–6005.
[15] For recent examples on the PdII-catalyzed synthesis of car-
bazoles by double aromatic CÀH bond activation, see: a) B.
Liꢄgault, D. Lee, M. P. Huestis, D. R. Stuart, K. Fagnou, J.
Org. Chem. 2008, 73, 5022–5028; b) T. Watanabe, S. Oishi,
N. Fujii, H. Ohno, J. Org. Chem. 2009, 74, 4720–4726; c) R.
Forke, K. K. Gruner, K. E. Knott, S. Auschill, S. Agarwal,
R. Martin, M. Bçhl, S. Richter, G. Tsiavaliaris, R. Fedorov,
D. J. Manstein, H. O. Gutzeit, H.-J. Knçlker, Pure Appl.
Chem. 2010, 82, 1975–1991, and references cited herein.
[16] For selected examples of direct arylation of anilides, see:
a) Y. Kametani, T. Satoh, M. Miura, M. Nomura, Tetrahe-
dron Lett. 2000, 41, 2655–2658; b) D. Kalyani, N. R.
Received: July 11, 2011
Accepted: September 23, 2011
Published online: February 14, 2012
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