Novel strategy for the synthesis of chiral pseudo-ortho-substituted hydroxy[2.2]paracyclophane-based ligands from the resolved 4-bromo-12-hydroxy[2.2]paracyclophane as a parent compound

Article abstract of DOI:10.1016/j.tetasy.2007.12.010

A simple and efficient resolution of racemic 4-bromo-12-hydroxy[2.2]paracyclophane into its enantiomers via diastereomeric esters with (1S)-(-)-camphanic acid was carried out. New synthetic routes to enantiomerically pure 4,12-dihydroxy- and 4-hydroxy[2.2]paracyclophanes starting from the enantiomers of an intermediate 4-bromo-12-hydroxy[2.2]paracyclophane are proposed.

Full text of DOI:10.1016/j.tetasy.2007.12.010

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 216–222
Novel strategy for the synthesis of chiral pseudo-ortho-substituted
hydroxy[2.2]paracyclophane-based ligands from the resolved 4-bromo-
1
2-hydroxy[2.2]paracyclophane as a parent compound
Roman Zhuravsky, Zoya Starikova, Evgenii Vorontsov and Valeria Rozenberg*
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, 119991 Moscow, Russia
Received 15 November 2007; accepted 19 December 2007
Abstract—A simple and efficient resolution of racemic 4-bromo-12-hydroxy[2.2]paracyclophane into its enantiomers via diastereomeric
esters with (1S)-(ꢀ)-camphanic acid was carried out. New synthetic routes to enantiomerically pure 4,12-dihydroxy- and 4-
hydroxy[2.2]paracyclophanes starting from the enantiomers of an intermediate 4-bromo-12-hydroxy[2.2]paracyclophane are proposed.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
as efficient chiral ligands and auxiliaries for asymmetric
synthesis and catalysis.
1
5
Hydroxy-based (e.g., O,O-, N,O-, P,O-, etc.) ligands for
asymmetric synthesis and catalysis belong to the most effi-
In addition to these ortho-derivatives, pseudo-ortho-disub-
stituted [2.2]paracyclophanes have successfully been used
1
15
cient and widely used chiral inductors. In [2.2]paracyclo-
2
phane chemistry, the key compound for the synthesis of
as ligands. However, there are a few examples of the hydr-
oxy-based pseudo-ortho-ligands, for example, 4,12-dihydr-
oxy[2.2]paracyclophane [PHANOL, a paracyclophanyl
such inductors has been 4-hydroxy[2.2]paracyclophane 1
3
4
(
Fig. 1). The methods of synthesis and chemical or enzy-
5
16
matic resolution of this compound into enantiomers have
attracted considerable attention. Typically, phenol 1 under-
goes ortho-regioselective substitution reactions; therefore,
ligands based on this compound are mainly its ortho-deriv-
atives. For instance, phenol 1 was used as the parent com-
analog of the well-known ligand BINOL] 8, oxazolinyl-
1
7
cyclophanyl derivatives 9, and a planar chiral chelating
1
8
imidazolium ligands 10 (Fig. 2).
The synthesis of these ligands in enantiomerically pure
form was carried out either from optically active starting
3
c,4a,6
pound for the synthesis of FHPC 2 (R = H),
a
1
9
paracyclophanyl analog of salicylic aldehyde; ortho-
(R )-4,12-dibromo[2.2]paracyclophane 11 (ligands 9 and
p
7
18
hydroxyketones 2 (R = Me, Ph) in turn served as the
10), or by the resolution of the final product (ligand
1
6a,21
starting compounds in the synthesis of a family of
8).
The efficient synthesis of the racemic 4-bromo-12-
8
bi-, tri- and tetradentate imine ligands and chiral amino-
hydroxy[2.2]paracyclophane 12 and its resolution into
9
10
11
20
phenols]; 1,3-oxazol-2-one 3; ‘bridged’ biphenols 4;
enantiomers prompted us to elaborate a new approach
1
2
diparacyclophanyl biphenol 5; and arylparacyclophanes
(X = OH, OMe).
of a class of bis-bifunctional ligands 7 by oxidation of 1
to the corresponding quinone followed by the addition
of functionally substituted aryllithium derivatives. Com-
pounds 2–7 (Fig. 1) and their derivatives proved themselves
to enantiomerically pure hydroxy-based pseudo-ortho-
ligands using the intermediate resolved bromophenol 12
2
a,13
6
Phenol 1 was also used in the design
2
d
as a source of chirality. It should be noted that (R )-12
p
1
4
could also be obtained from (R )-4,12-dibromo[2.2]para-
p
1
8,19
cyclophane 11.
In this work, we report on the experimental details of the
synthesis of rac-12, its resolution into enantiomers via dia-
stereomeric esters with (1S)-(ꢀ)-camphanic acid, and new
synthetic routes to enantiomerically pure PHANOL 8
and 4-hydroxy[2.2]paracyclophane (Fig. 3).
*
0
Corresponding author. Fax: +7 499 135 50 85; e-mail: ineos-ghkl@
yandex.ru
957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.12.010

R. Zhuravsky et al. / Tetrahedron: Asymmetry 19 (2008) 216–222
217
O
N
H
O
3
OH
OH OH
R'
R
C
O
R
4
OH
2
R
R
1
OH
X
X
HO
HO
OH
OH
5
7
X
6
Figure 1. 4-Hydroxy[2.2]paracyclophane 1, a ‘parent’ compound for paracyclophanyl hydroxy-based ligands.
R2
R1
2
. Results and discussion
O
2.1. Synthesis and resolution of 4-bromo-12-hydroxy-
[2.2]paracyclophane 12 into enantiomers
OMe
N
OH
R
N
N
OH
Racemic bromophenol 12 was synthesized from the start-
ing racemic dibromide 11 by selective replacement of a bro-
mine atom by the hydroxy group
OH
Ph Ph
18,20
and then resolved
8
9
10
into enantiomers using (1S)-(ꢀ)-camphanic acid, a known
4a,21
reagent for the resolution of racemic hydroxy-substituted
Figure 2. First examples of pseudo-ortho-[2.2]paracyclophane ligands
having a hydroxy functional moiety.
paracyclophane derivatives.
Diastereomeric esters 13
were obtained in high yield (98%) by treating rac-12 with
(
1S)-camphanoyl chloride synthesized from (1S)-(ꢀ)-
2
2
camphanic acid and thionyl chloride (Scheme 1). The
esterification readily proceeds in pyridine at room temper-
ature in the presence of a small excess of camphanoyl
chloride.
Br
OH
The preparative resolution of diastereomeric esters 13 was
performed by column chromatography on silica gel (meth-
ylene chloride/ethyl acetate = 100:1 mixture as eluent). The
combined fraction (R 0.50) contained 98% of (S ,S)-13
Br
Br
rac-11
rac-12
f
p
and the combined fraction (R 0.39) gave 88% of (R ,S)-
f
p
Resolution
13. To isolate the enantiomers of compound 12, esters
(
S ,S)- and (R ,S)-13 were hydrolyzed with KOH in meth-
p
p
OH
HO
anol at room temperature for 2.5 h. The enantiomers, (S )-
p
(Rp)-12
(
Sp)-12
and (R )-12, were synthesized in almost quantitative yields.
p
Their enantiomeric purity exceeded 99%, which was con-
Ò
HO
(Sp)-PHANOL, 8
firmed by HPLC on a Chiralpak AD-H column (retention
time t = 37.25 min for (R )-12 and t = 41.00 min for
S )-12). The absolute configuration of (S )-12 enantiomer
p p
R
p
S
(
Rp)-1
(
Figure 3. New synthetic routes to compounds 1 and 8 starting from
enantiomers of 4-bromo-12-hydroxy[2.2]paracyclophane 12.
was determined by X-ray analysis of camphanoate (S ,S)-
13 (Fig. 4).
p

218
R. Zhuravsky et al. / Tetrahedron: Asymmetry 19 (2008) 216–222
oxy[2.2]paracyclophane 14 affording enantiomerically pure
1
6a
Br
PHANOL. This procedure takes a long time to complete
more than 14 days) and results in low overall yield [(R )-8,
(
O
O
b
p
(Sp)-12
30%; (S )-8, 24%; from dibromide 11]. A more traditional
procedure for the resolution of 8 was developed by Jiang.
It involves the synthesis of diastereomeric esters of (1S)-
camphanic acid 15 followed by their separation by flash
p
2
1
O
O
(
Sp,S)-13
chromatography and reduction with LiAlH . In this case,
the yield of each enantiomer of compound 8 was 36% (cal-
culated with respect to the racemic dibromide 11).
a
4
rac-12
O
O
The strategy for the synthesis of enantiomerically pure com-
pound 8 proposed in this work involves the selective
replacement of one bromine atom in racemic 11 by the hy-
droxy group to give bromophenol 12 followed by resolution
of rac-12 and the synthesis of the target optically active 8
from the enantiomers of 12 (Scheme 3A). Racemic 12 was
obtained in 93% yield following the known procedure for
O
b
(Rp)-12
O
Br
(
Rp,S)-13
Scheme 1. Resolution of racemic 4-bromo-12-hydroxy[2.2]paracyclo-
phane 12 into enantiomers. Reagents and conditions: (a) (1S)-(ꢀ)-
camphanoyl chloride, Py, room temperature, 6 h, then chromatography
1
8
the synthesis of (R )-12 from (R )-11 and resolved into
p
p
enantiomers using (1S)-camphanic acid, as described in Sec-
on silica gel, 98% for (S
room temperature, 2 h, 97% for (S
p
,S)-13 and 88% for (R
)-12 and 97% for (R
p
,S)-13; (b) KOH, MeOH,
tion 2.1. Lithiation of (S )-12 with n-BuLi (3.2 equiv) in
p
p
p
)-12.
THF at ꢀ78 °C followed by treatment with B(OMe) and
3
oxidation with H O resulted in a mixture of (S )-8 and
2
2
p
2
.2. Synthesis of enantiomerically pure PHANOL 8
(S )-1. The formation of phenol 1 in this reaction can be
p
explained by insufficient reactivity of the intermediate
PHANOL16 8 is considered to be a paracyclophanyl analog
lithium derivative with respect to the B(OMe) . The com-
3
1
b
of the known BINOL ligand. However, biphenol 8 has
never been used as an asymmetric ligand in catalysis. This
can to some extent be due to the difficulties in the synthesis
pounds synthesized were easily separated by preparative
chromatography on SiO . The yield of (S )-8 in this reac-
2
p
tion was 49% (42% with respect to the starting racemic
1
6,21
of its enantiomers.
dibromide 11), being higher than the yield of (S )-8 synthe-
p
sized as reported by Braddock and Jiang (24% and 36%,
respectively; see Scheme 2). The advantage of our approach
consists in the possibility of isolation of not only compound
8, but also enantiomerically pure 4-hydroxy[2.2]paracyclo-
Racemic PHANOL 8 was first synthesized by Cram and
Reich in 1969 from dibromide 11 (Scheme 2) using simul-
taneous replacement of both the bromines by lithium (n-
2
3
BuLi/Et O) followed by oxidation with nitrobenzene. The
phane (S )-1 (32%), a valuable parent compound in the
2
p
desired diol was obtained in a low yield (16% only). Recen-
chemistry of [2.2]paracyclophane (Fig. 1).
1
6a
tly,
Braddock reported a higher yield of 8 (35–45%) in
the reaction carried out in THF instead of Et O.
Taking into account the fact that the bromine atom in
the bromophenol molecule can not only be replaced by a
functional group, but also be eliminated, we carried out
2
To resolve compound 8 into its enantiomers, two routes
were proposed (Scheme 2). Braddock reported a lipase-cat-
alyzed enzymatic kinetic resolution of racemic 4,12-bisacet-
the lithiation of enantiomerically pure (R )-12 with an excess
p
of n-BuLi. Subsequent hydrolysis gave enantiomerically
p
Figure 4. Molecular structure of (+)-(S ,S)-13.

R. Zhuravsky et al. / Tetrahedron: Asymmetry 19 (2008) 216–222
219
c16a
rac-14, Z = Ac
3
0% from 11
(Rp)-8
36% from 11
24% from 11
(Sp)-8
36% from 11
OH
OZ
a or b
c or d
11
OZ
d21
OH
rac-PHANOL, 8
rac-15, Z = (1S)-camphanoyl
Scheme 2. Synthetic routes to racemic and enantiomerically pure PHANOL 8. Reagents and conditions: (a) n-BuLi in Et
2
O, then PhNO
2
, 16%; (b) n-BuLi
in THF, ꢀ78 °C, then PhNO
2
, 35–45%; (c) NaH, AcCl, then enzymatic resolution using the Candida rugosa lipase; (d) (1S)-(ꢀ)-camphanoyl chloride, Py,
4
room temperature, then chromatography on silica gel, then LiAlH
, THF, reflux, 6 h.
HO
d
+
(A)
(B)
(Sp)-12
HO
HO
a
b, c
(S
p)-PHANOL, 8
(S
p)-1
rac-11
rac-12
42% from rac-11
28% from rac-11
e
(
R
p)-12
(R
p)-1
Scheme 3. New synthetic routes to enantiomerically pure PANOL 8 and 4-hydroxy[2.2]paracyclophane 1. Reagents and conditions: (a) n-BuLi, THF,
78 °C, 0.5 h, B(OMe) , ꢀ78 °C to room temperature, then H /NaOH, 93%; (b) (1S)-(ꢀ)-camphanoyl chloride, Py, room temperature, 6 h, then
chromatography on silica gel, 98% for (S ,S)-13 and 88% for (R ,S)-13; (c) KOH, MeOH, room temperature, 97% for (S )-12 and 97% for (R )-12; (d) n-
BuLi, THF, 0 °C, 2 h, then recooled to ꢀ78 °C, B(OMe) , ꢀ78 °C to room temperature, then H /NaOH, 49% for (S)-8 and 32% for (S)-1; (e) n-BuLi,
THF, 0 °C, 3 h, then H O, 98%.
ꢀ
3
2 2
O
p
p
p
p
3
2 2
O
2
pure phenol 1 (98%) as the only reaction product (Scheme
B). Previously, the enantiomers of 1 was obtained by resolu-
for the synthesis of ortho-hydroxyparacyclophane-based
ligands bearing a bulky bromine substituent in the
pseudo-ortho-position relative to the hydroxy group.
3
4
,5
tion of rac-1 synthesized from 4-bromo[2.2]paracyclo-
3
26
phane. The new route to optically active phenol 1
Recently, we have shown that, similarly to phenol 1,
presented in Scheme 3B seems to be promising because it
allows the resolution of intermediate bromophenol 11 to pro-
ceed more readily compared to the resolution of phenol 1.
the enantiomerically pure compound 12 can be used as a
chiral inductor, namely, recoverable auxiliary reactant in
the asymmetric allylboronation of benzaldehyde (ee of
the product, 3-buten-1-phenyl-1-ol, up to 59%).
4
,5
The presence of the bromine substituent in 12 offers pros-
pects for the synthesis of a variety of pseudo-ortho-disubsti-
tuted paracyclophanes based on 12. For instance, lithiation
of 12 followed by treatment of the reaction mixture with N-
3. Conclusion
2
4
formylpiperidine resulted in pseudo-ortho-FHPC 16. The
bi- and tridentate imine ligands based on compound 16 ap-
peared to be efficient in the asymmetric addition of diethyl-
Summing up, we have synthesized racemic 4-bromo-12-
hydroxy[2.2]paracyclophane 12 and elaborated a simple
and efficient procedure for its resolution into enantiomers.
New routes to enantiomerically pure PHANOL 8 and 4-
hydroxy[2.2]paracyclophane 1 using enantiomers of 12
were proposed. Further use of bromophenol 12 in the de-
sign of enantiomerically pure pseudo-ortho-disubstituted
paracyclophanes and their application as ligands for asym-
metric catalytic reactions is now in progress and will be re-
ported elsewhere.
2
5
zinc to benzaldehyde. Taking biphenol 17 as an example,
we proposed a strategy of the synthesis of bifunctional
aryl[2.2]paracyclophanyl ligands using Pd-catalyzed Suzuki
2
a
coupling of bromophenol 12 with arylboronic acids.
OH
OH
OH
4. Experimental
CHO
4.1. General
ps-ortho
-FHPC, 16
17
It is important that 4-bromo-12-hydroxy[2.2]paracyclo-
phane 12 is an analog of phenol 1 and can thus be used
Pyridine was distilled twice from KOH. Ethyl acetate was
washed with saturated aq K CO , dried with CaCl , and
2
3
2

220
R. Zhuravsky et al. / Tetrahedron: Asymmetry 19 (2008) 216–222
distilled from anhydrous K CO . THF was distilled from
–CH ); 1.21 (s, 3H, –CH ); 1.28 (s, 3H, –CH ); 1.78–1.91
3 3 3
2
3
sodium benzophenone ketyl under argon before use. All
reactions with n-BuLi were performed under an atmo-
sphere of argon. Benzene and toluene were distilled from
sodium. (1S)-(ꢀ)-Camphanic acid was purchased from
(m, 1H); 2.01–2.13 (m, 1H); 2.27–2.39 (m, 1H); 2.58–2.77
(m, 2H); 2.78–2.89 (m, 1H); 2.91–3.25 (m, 5H); 3.37–3.50
(m, 1H); 6.42–6.57 (m, 3H, aromatic H); 6.63 (d,
3
J = 7.8, 1H, aromatic H); 6.79 (s, 1H, aromatic H); 7.00
2
2
+
Fluka. (1S)-(ꢀ)-Camphanoyl chloride was synthesized
following the literature. Optical rotations were recorded
on Perkin–Elmer 241 instrument in a thermostatted cell.
(s, 1H, aromatic H); MS (EI), m/z (rel): 484 (13, M ),
+
482 (14, M ), 403 (17), 357 (14), 317 (14), 304 (12), 302
(18), 300 (43), 224 (18), 223 (100), 222 (12), 221 (19), 185
(11), 184 (16), 182 (15), 179 (12), 167 (11), 149 (17), 135
(16), 125 (30), 122 (15), 121 (16), 120 (74), 109 (41), 103
(20). Anal. Calcd for C H BrO : C, 64.60; H, 5.63; Br,
1
H spectra were recorded on a Bruker AMX-400 spectro-
meter at 400.13 MHz in CDCl . The residual signal of
3
the solvent protons with the chemical shifts d 7.27 (CDCl3)
was used as internal standards. Mass spectra were obtained
on a KRATOS MS890A mass spectrometer (70 eV). TLC-
analyses were performed on silica gel precoated SORBFIL
plates PTLC-A-UV (Sorbpolimer). Column chromatogra-
phy was performed on Kieselgel 60, 230–400 mesh ASTM
26
27
4
16.53. Found: C, 64.57; H, 5.54; Br, 16.28.
4
.4. (R )-(ꢀ)-4-Bromo-12-hydroxy[2.2]paracyclophane
p
(R )-12
p
(
Merck). Enantiomeric analyses were carried out by HPLC
KOH (0.636 g, 11.4 mmol) was added to a suspension of
R ,S)-13 (1.300 g, 2.69 mmol) in MeOH (100 mL). The
Ò
on Chiralpak AD-H analytical column using hexane/2-
propanol (100/4) as an eluent (1 mL/min) detected at
2
(
p
mixture was stirred for 2 h at room temperature, diluted
with saturated aqueous NaCl (100 mL) and C H
54 nm.
6
6
(
50 mL) vigorously stirred for 0.5 h. The organic layer
4
.2. rac-4-Bromo-12-hydroxy[2.2]paracyclophane 12
was separated and the aqueous layer washed with C H
6
6
(
2 ꢁ 50 mL). The combined organic layer was dried over
Racemic 12 (93%) was synthesized according to a proce-
anhydrous Na SO , concentrated under reduced pressure
and chromatographed (C H ) to give bromophenol
2
4
1
8
dure described in the literature for (R )-12; mp 150.5–
p
6
6
1
53 °C; Anal. Calcd for C H BrO: C, 63.38; H, 4.99;
1
6
15
(
R )-(ꢀ)-12 (0.791 g, 97%); >99% ee by HPLC analysis
1
p
Br, 26.35. Found: C, 63.34; H, 4.88; Br, 26.25. The H
NMR and MS data are in a good agreement with those
(t = 37.25, t = 41.00); mp 149–151 °C (Ref. 18 mp 149–
S
R
1
53 °C).
of (R )-12.
p
4
.5. (S )-(+)-4-Bromo-12-hydroxy[2.2]paracyclophane
p
4
.3. (S ,S)-13 and (R ,S)-13
p p
(Sp)-12
To (1S)-(ꢀ)-camphanoyl chloride (1.46 g, 6.73 mmol) was
added a solution of rac-12 (1.70 g, 5.61 mmol) in pyridine
Compound (S )-(+)-12 was obtained by the same method
p
from (S ,S)-13 in 97% yield; >99% ee by HPLC analysis;
p
(
6
7 mL). The mixture was stirred at room temperature for
h, diluted with H O (50 mL), and vigorously stirred until
2
0
mp 149–152 °C; ½aꢂ ¼ þ24:4 (c 0.80, C H ); Anal. Calcd
D
6
6
2
for C H BrO: C, 63.38; H, 4.99; Br, 26.35. Found: C,
1
6
15
a white precipitate was obtained. The precipitate was
removed by filtration, washed with 2 M HCl (100 mL),
1
6
3.11; H, 4.89; Br, 25.81. The H NMR and MS data are
in a good agreement with those of (R )-12.
1
8
p
H O (5 ꢁ 100 mL), and hexane (30 mL), and dried in
2
vacuo to yield a mixture of diastereomeric esters 13
(
2.71 g, 99%), which were purified by chromatography on
4.6. (S )-(ꢀ)-PHANOL 8
p
silica gel using CH Cl –AcOEt (100:1) as the eluent.
2
2
To a stirred solution of (S )-(+)-12 (0.150 g, 0.495 mmol)
p
(
S ,S)-13, TLC R = 0.50 (CH Cl –AcOEt, 100:1), eluted
in THF (2 mL) at 0 °C under argon, n-BuLi (0.49 mL of
3.20 M solution in hexane, 1.583 mmol, 3.2 equiv) was
added via syringe. The reaction mixture was stirred for
p
f
2
2
20
first; 1.329 g (98%); mp 144.5–145 °C; ½aꢂ ¼ þ19:0 (c
D
1
0
–
(
(
(
.97, C H ); H NMR (CDCl , 400 MHz): d 1.19 (s, 3H,
6 6 3
CH ); 1.22 (s, 3H, –CH ); 1.28 (s, 3H, –CH ); 1.74–1.85
2 h at 0 °C, recooled to ꢀ78 °C and B(OMe) (0.257 g,
3
3
3
3
m, 1H); 1.96–2.08 (m, 1H); 2.13–2.25 (m, 1H); 2.54–2.89
m, 3H); 2.98–3.27 (m, 5H); 3.38–3.49 (m, 1H); 6.43–6.56
0.28 mL, 2.47 mmol) was added. The reaction mixture
was warmed up to room temperature overnight. Then,
NaOH (0.100 g, 2.5 mmol) in H O (0.5 mL) and H O
2
3
m, 3H, aromatic H); 6.63 (d, J = 7.8, 1H, aromatic H);
2
2
6
.78 (s, 1H, aromatic H); 7.00 (s, 1H, aromatic H); MS
(0.32 mL of 30% aqueous solution, 2.82 mmol) was added.
The mixture was stirred for 3 h at room temperature, di-
luted with saturated aqueous NaCl (5 mL) and toluene
(5 mL). The organic layer was separated and the aqueous
layer washed with 1:1 mixture of toluene and THF
(3 ꢁ 10 mL). The combined organic layer was dried over
anhydrous Na SO , concentrated under reduced pressure
+
+
(
(
(
(
EI), m/z (rel): 484 (9, M ), 482 (14, M ), 403 (15), 357
11), 317 (12), 304 (14), 302 (17), 300 (42), 224 (15), 223
100), 222 (11), 221 (19), 185 (11), 184 (16), 182 (13), 178
12), 167 (15), 149 (38), 135 (11), 125 (23), 121 (16), 120
74), 109 (33), 103 (20). Anal. Calcd for C H BrO : C,
(
2
6
27
4
6
1
4.60; H, 5.63; Br, 16.53. Found: C, 64.41; H, 5.51; Br,
6.42.
2
4
and the residue was purified by chromatography on SiO2
(
R 0.30; hexane/EtOAc, 2:1), to yield compound (S )-
f
p
1
6a
(
R ,S)-13, TLC R = 0.39 (CH Cl –AcOEt, 100:1), eluted
(ꢀ)-8
(0.058 g, 49%). From combined fractions with
p
f
2
2
20
3c,4
next; 1.199 g (88%); mp 155–156 °C; ½aꢂ ¼ ꢀ54.8 (c 0.75,
R = 0.53 the compound (S )-(ꢀ)-1
(0.035 g, 32%) was
D
f
p
1
C H ); H NMR (CDCl , 400 MHz): d 1.14 (s, 3H,
obtained.
6
6
3

R. Zhuravsky et al. / Tetrahedron: Asymmetry 19 (2008) 216–222
221
4
.7. (R )-(+)-4-Hydroxy[2.2]paracyclophane (R )-1
p
http://www.ccdc.cam.uk/conts/retrieving.html (or from
the CCDC, 12 Union Road, Cambridge CB2 1EZ; fax:
+44 1223 335 033; or deposit@ccdc.cam.ac.uk). Any re-
quest to the CCDC for data should quote the full literature
citation and CCDC reference numbers.
p
To a stirred solution of (R )-(ꢀ)-12 (0.045 g, 0.148 mmol)
p
in THF (2 mL) at 0 °C under argon, n-BuLi (0.14 mL of
3
.27 M solution in hexane, 0.445 mmol, 3.0 equiv) was
added. The reaction mixture was stirred for 3 h at 0 °C
and H O (3.0 mL) was added. The organic layer was sepa-
2
rated and the aqueous layer washed with benzene
Acknowledgements
(
3 ꢁ 4 mL). The combined organic layer was dried over
anhydrous Na SO , concentrated under reduced pressure
2
4
Financial support of this work by the Russian Foundation
for Basic Research (Project No. 06-03-33086) is gratefully
acknowledged. The authors are grateful to Professor Va-
dim A. Davankov and Dr. Mikhail M. Il’in for the enantio-
meric analysis (INEOS RAS, Moscow, Russia).
and the residue was purified by chromatography on SiO
2
3
c,4
(
benzene), to yield compound (R )-(ꢀ)-1
(0.032 g, 98%).
p
4
.8. Crystallographic analysis of (S ,S)-13
p
Colourless, needle-like crystals were obtained from EtOH,
C H BrO , M = 483.39, dimension: 0.5 ꢁ 0.4 ꢁ 0.3 mm,
2
6
27
4
r
References
crystal system: orthorhombic, space group: P2 2 2 ,
1
1 1
˚
˚
˚
a = 11,274(3) A,
b = 13.033(4) A,
c = 15.102(4) A,
1
2
. See, for example: (a) Noyori, R. Asymmetric Catalysis in
Organic Synthesis; Willey & Sons: New York, 1994; (b)
Brunel, J. M. Chem. Rev. 2005, 105, 857–898; (c) Baleiz a˜ o, C.;
Garcia, H. Chem. Rev. 2006, 106, 3987–4043; (d) Pu, L.; Yu,
H.-B. Chem. Rev. 2001, 101, 3987–4043, pp 757–824.
. See, for example: (a) Rozenberg, V. I.; Zhuravsky, R. P.;
Sergeeva, E. V. Chirality 2006, 18(2), 95–102; (b) Vorontsova,
N. V.; Vorontsov, E. V.; Sergeeva, E. V.; Rozenberg, V. I.
Tetrahedron Lett. 2006, 47, 2357–2360; (c) Sergeeva, E. V.;
Rozenberg, V. I.; Antonov, D. Yu.; Vorontsov, E. V.;
Starikova, Z. A.; Fedyanin, I. V.; Hopf, H. Chem. Eur. J.
3
3
˚
V = 2219(1) A , Z = 4, D
l(Mo-K ) = 1.883 cm , Tmin/Tmax: 0.587/0.928, h range:
= 1.447 g/cm , abs. coeff.
calcd
ꢀ1
a
2
.06–29.50°, completeness of dataset: 98.0%, number of
reflections collect: 17,385, number of independent reflec-
tions: 3396 (Rint = 0.0605), number of observed reflec-
tions [I > 2r(I)]: 2930, number of parameters: 280. Final
R
indices: R = 0.0303, wR = 0.0696. Weighting
1 2
2
ꢀ
1
2
2
2
2
scheme:
w
¼ r ðF Þ þ ðaPÞ þ bP; P ¼ 1=3ðF þ 2F Þ,
o
o
c
a = 0.0383, b = 0.0000. F(000) = 1000, GOOF 0.988,
Largest diff. peak and hole [e A ]: 0.982 and ꢀ0.603.
ꢀ
3
˚
2
005, 11, 6944–6961; (d) Vorontsova, N.; Vorontsov, E.;
Antonov, D.; Starikova, Z.; Butin, K.; Br a¨ se, S.; H o¨ fener, S.;
Single-crystal X-ray diffraction experiments were carried
out with a Bruker SMART 1000 CCD area detector, using
Rozenberg, V. Adv. Synth. Catal. 2005, 347, 129–135.
3. (a) Hoffman, W.; Detrick, K. Synthesis 1983, 107, 107–109;
(b) Krohn, K.; Reiger, H.; Hopf, H.; Barret, D.; Jones, P. G.;
Doring, D. Chem. Ber. 1990, 123, 1729–1732; (c) Cipiciani,
A.; Fringuelli, F.; Mancini, V.; Piermatti, O.; Pizzo, F. J. Org.
Chem. 1997, 62, 3744–3747; (d) Hitchcock, P. B.; Rowlands,
G. J.; Parmar, R. Chem. Commun. 2005, 4219–4221.
. (a) Rozenberg, V. I.; Danilova, T. I.; Sergeeva, E. V.;
Vorontsov, E. V.; Starikova, Z. A.; Korlyukov, A.; Hopf,
H. Eur. J. Org. Chem. 2002, 468–477; (b) Zhang, T.-Z.; Dai,
L.-X.; Hou, X.-L. Tetrahedron: Asymmetry 2007, 18, 251–259.
5. (a) Cipiciani, A.; Fringuelli, F.; Mancini, V.; Piermatti, O.;
Scappini, A. M.; Ruzziconi, R. Tetrahedron 1997, 53, 11853–
11858; (b) Pamperin, D.; Ohse, B.; Hopf, H.; Pietzsch, M. J.
Mol. Catal., B: Enzym. 1998, 5, 317–319; (c) Pamperin, D.;
Schulz, C.; Hopf, H.; Syldatk, C.; Pietzsch, M. Eur. J. Org,
Chem. 1998, 1441–1445; (d) Cipiciani, A.; Bellezza, F.;
Fringuelli, F.; Silvestrini, M. G. Tetrahedron: Asymmetry
graphite
monochromated
Mo-Ka
radiation
˚
(
k = 0.71073 A, x-scans with a 0.3° step in x and 10 s
per frame exposure, 2h < 59°) at 120 K. Low temperature
of the crystals was maintained with a Cryostream (Oxford
Cryosystems) open-flow N gas cryostat. Reflection intensi-
2
4
ties were integrated using SAINT software [SMART V5.051
and SAINT V5.00, Area detector control and integration
software, 1998, Bruker AXS Inc., Madison, WI-53719,
USA] and semi-empirical method SADABS [G. M. Sheld-
rick, SADABS, 1997, Bruker AXS Inc., Madison, WI-53719,
USA].
The structures were solved by direct method and refined by
2
the full-matrix least-squares against F in anisotropic (for
no-hydrogen atoms) approximation. The H(C) atoms were
placed in geometrically calculated positions and were
refined in isotropic approximation in riding model with
2
001, 12, 2277–2281.
6
. (a) Rozenberg, V.; Kharitonov, V.; Antonov, D.; Sergeeva,
E.; Aleshkin, A.; Ikonnikov, N.; Orlova, S.; Belokon’, Yu.
Angew. Chem., Int. Ed. Engl 1994, 33, 91–92; (b) Hopf, H.;
Barrett, D. G. Liebigs Ann. 1995, 449–451; (c) Antonov, D.
Yu.; Belokon’, Yu. N.; Ikonnikov, N. S.; Orlova, S. A.;
Pisarevsky, A. P.; Raevsky, N. I.; Rozenberg, V. I.; Sergeeva,
E. V.; Struchkov, Yu. T.; Tararov, V. I.; Vorontsov, E. V. J.
Chem. Soc., Perkin Trans. 1 1995, 14, 1873–1879.
the U (H) parameters equal to 1.2 U (Ci), for methyl
iso
eq
groups equal to 1.5 U (Cii), where U(Ci) and U(Cii) are,
eq
respectively, the equivalent thermal parameters of the
atoms to which the corresponding H atoms are bonded.
All calculations were performed on an IBM PC/AT using
the SHELXTL software [G. M. Sheldrick, SHELXTL-97, Ver-
sion 5.10, Bruker AXS Inc., Madison, WI-53719, USA].
7
8
. Rozenberg, V.; Danilova, T.; Sergeeva, E.; Vorontsov, E.;
Starikova, Z.; Lysenko, K.; Belokon’, Yu. Eur. J. Org. Chem.
2
000, 3295–3303.
. (a) Danilova, T. I.; Rozenberg, V. I.; Vorontsov, E. V.;
Starikova, Z. A.; Hopf, H. Tetrahedron: Asymmetry 2003, 14,
Atomic coordinates, bond lengths, bond angles and ther-
mal parameters have been deposited at the Cambridge
Crystallographic Data Centre (CCDC), deposition number
1
375–1383; (b) Danilova, T. I.; Rozenberg, V. I.; Sergeeva, E.
V.; Starikova, Z. A.; Br a¨ se, S. Tetrahedron: Asymmetry 2003,
14, 2013–2019; (c) Danilova, T. I.; Rozenberg, V. I.;
6
54011. These data can be obtained free of charge via

222
R. Zhuravsky et al. / Tetrahedron: Asymmetry 19 (2008) 216–222
Starikova, Z. A.; Brase, S. Tetrahedron: Asymmetry 2004, 15, Weinheim, 2004; pp 435–462; (b) Gibson, S. E.; Knight, J. D.
2
1
23–229; (d) Vetter, A. H.; Berkessel, A. Tetrahedron Lett.
998, 39, 1741–1744; (e) Belokon’, Yu.; Moskalenko, M.;
Org. Biomol. Chem. 2003, 1256–1269.
16. (a) Braddock, D. C.; MacGilp, I. D.; Perry, B. G. J. Org.
Chem. 2002, 67, 8679–8681; (b) Braddock, D. C.; MacGilp, I.
D.; Perry, B. G. Synlett 2003, 1121–1124; (c) Braddock, D.
C.; MacGilp, I. D.; Perry, B. G. Adv. Synth. Catal. 2004, 346,
1117–1130.
17. Wu, X.-W.; Hou, X.-L.; Dai, L.-X.; Tao, J.; Cao, B.-X.; Sun,
J. Tetrahedron: Asymmetry 2001, 12, 529–532.
18. Focken, T.; Rudolph, J.; Bolm, C. Synthesis 2005, 3, 429–
436.
Ikonnikov, N.; Yashkina, L.; Antonov, D.; Vorontsov, E.;
Rozenberg, V. Tetrahedron: Asymmetry 1997, 8, 3245–3250;
(
f) Br a¨ se, S.; Dahmen, S.; H o¨ fener, S.; Lauterwasser, F.;
Kreis, M.; Ziegert, R. E. Synlett 2004, 15, 2647–2669.
. (a) Dahmen, S.; Br a¨ se, S. Tetrahedron: Asymmetry 2001, 12,
845–2850; (b) Rozenberg, V. I.; Danilova, T. I.; Sergeeva, E.
9
2
V.; Shouklov, I. A.; Starikova, Z. A.; Hopf, H.; K u¨ hlein, K.
Eur. J. Org. Chem. 2003, 432–440.
1
1
0. Cipiciani, A.; Fringuelli, F.; Piermatti, O.; Pizzo, F.; Ruzzi-
coni, R. J. Org. Chem. 2002, 67, 2665–2670.
1. Rozenberg, V. I.; Antonov, D. Yu.; Zhuravsky, R. P.;
Vorontsov, E. V.; Khrustalev, V. N.; Ikonnikov, N. A.;
Belokon’, Yu. N. Tetrahedron: Asymmetry 2000, 11, 2683–
19. Rossen, K.; Pye, P. J.; Maliakal, A.; Volante, R. P. J. Org.
Chem. 1997, 62, 6462–6463.
20. Zhuravsky, R. P.; Rozenberg, V. I.; Antonov, D. Yu.;
Vorontsov, E. V.; Starikova, Z. A.; Modern Trends in
Organoelement and Polymer Chemistry, Abstract of paper,
Moscow, Russia, 2004, p 166.
2
693.
1
1
1
2. Wack, H.; France, S.; Hafez, A. M.; Drury, W. J., III;
21. Jiang, B.; Zhao, X.-L. Tetrahedron: Asymmetry 2004, 15,
1141–1143.
22. Gerlah, H. Helv. Chim. Acta 1978, 61, 2773–2776.
23. Reich, H. J.; Cram, D. J. J. Am. Chem. Soc. 1969, 91, 3527–
3533.
24. Antonov, D. Yu.; Danilova, T. I.; Vorontsov, E. V.;
Starikova, Z. A.; Rozenberg, V. I. Modern Trends in
Organoelement and Polymer Chemistry, Moscow, Russia,
2004, Abstract of paper, p 165.
25. Antonov, D. Y.; Rozenberg, V. I.; Danilova, T. I.; Starikova,
Z. A.; Hopf, H. Eur. J. Org. Chem., in press.
26. Vorontsova, N. V.; Zhuravsky, R. P.; Sergeeva, E. V.;
Vorontsov, E. V.; Starikova, Z. A.; Rozenberg, V. I. Izv.
Akad. Nauk, Ser. Khim. 2007, 11, 2149–2155.
Weatherwax, A.; Lectka, T. J. Org. Chem. 2004, 69, 4531–
4
533.
3. Rozenberg, V. I.; Antonov, D. Yu.; Zhuravsky, R. P.;
Vororntsov, E. V.; Starikova, Z. A. Tetrahedron Lett. 2003,
4
4, 3801–3804.
4. (a) Cram, D. J.; Day, A. C. J. Org. Chem. 1966, 31, 1227–
232; (b) Vorontsova, N. V.; Rozenberg, V. I.; Vorontsov, E.
1
V.; Antonov, D. Y.; Starikova, Z. A.; Bubnov, Yu. N. Izv.
Akad. Nauk, Ser. Khim. 2002, 8, 1369–1375, [Russ. Chem.
Bull. Int. Ed. (Engl. Transl.) 2002, 8, 1483–1490].
1
5. (a) Rozenberg, V. I.; Sergeeva, E. V.; Hopf, H. Cyclophanes
as Templates in Stereoselective Synthesis. In Modern Cyclo-
phane Chemistry; Gleiter, R., Hopf, H., Eds.; Wiley VCH: