Novel ligands based on bromosubstituted hydroxycarbonyl [2.2]paracyclophane derivatives: synthesis and application in asymmetric catalysis

Article abstract of DOI:10.1016/j.tetasy.2010.03.038

New planar-chiral hydroxycarbonyl [2.2]paracyclophane derivatives, 4-acetyl-13-bromo-5-hydroxy[2.2]paracyclophane (Br-A{cyrillic}N{cyrillic}R{cyrillic}S{cyrillic}, 63%) and 4-benzoyl-13-bromo-5-hydroxy[2.2]paracyclophane (Br-BHPC, 53%), were synthesized and reacted with the enantiomers of α-phenylethylamine to form corresponding Schiff bases, 12-bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-ethyl]-[2.2]paracyclophane and 12-bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-(phenyl)methylen-[2.2]paracyclophane. The diastereomers of the imines were resolved and their absolute configurations and consequently the corresponding configurations of the enantiomers of Br-A{cyrillic}N{cyrillic}R{cyrillic}S{cyrillic} were determined by X-ray diffraction. Enantiomerically pure Schiff bases were applied as ligands to form catalysts for the enantioselective addition reaction of diethylzinc with benzaldehyde where 1-phenylpropanol was obtained with 77-91% ee.

Full text of DOI:10.1016/j.tetasy.2010.03.038

Tetrahedron: Asymmetry 21 (2010) 731–738
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Novel ligands based on bromosubstituted hydroxycarbonyl
[2.2]paracyclophane derivatives: synthesis and application
in asymmetric catalysis
*
Natalia V. Vorontsova , Galina S. Bystrova, Dmitrii Yu. Antonov, Anna V. Vologzhanina, Ivan A. Godovikov,
Michail M. Il’in
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, 119991 Moscow, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
New planar-chiral hydroxycarbonyl [2.2]paracyclophane derivatives, 4-acetyl-13-bromo-5-hydroxy
[2.2]paracyclophane (Br-AHPC, 63%) and 4-benzoyl-13-bromo-5-hydroxy[2.2]paracyclophane (Br-BHPC,
53%), were synthesized and reacted with the enantiomers of a-phenylethylamine to form corresponding
Schiff bases, 12-bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-ethyl]-[2.2]paracyclophane and 12-
bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-(phenyl)methylen-[2.2]paracyclophane. The diastereo-
mers of the imines were resolved and their absolute configurations and consequently the corresponding
configurations of the enantiomers of Br-AHPC were determined by X-ray diffraction. Enantiomerically pure
Schiff bases were applied as ligands to form catalysts for the enantioselective addition reaction of diethyl-
zinc with benzaldehyde where 1-phenylpropanol was obtained with 77–91% ee.
Received 22 March 2010
Accepted 31 March 2010
Available online 11 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
tion of their Schiff bases as ligands in asymmetric diethylzinc addi-
tion to benzaldehyde.
A number of planar chiral ortho-hydroxycarbonyl [2.2]paracy-
clophane derivatives have been successfully used in enantiomeri-
cally pure forms in asymmetric synthesis and catalysis. For
example, 4-formyl-5-hydroxy[2.2]paracyclophane 1 (FHPC) has
been used as a chiral auxiliary in the asymmetric synthesis of
OH
OH
OH
a
-amino acids,1 and the asymmetric trimethylsilylcyanation of
CHO
COCH3
COPh
benzaldehyde.2 Asymmetric alkyl and alkenyl zinc complexes with
Schiff’s bases from a variety of hydroxycarbonyl [2.2]paracyclo-
phane derivatives, such as FHPC 1, 4-acetyl-5-hydroxy[2.2]paracy-
clophane 2 (AHPC), 4-benzoyl-5-hydroxy[2.2]paracyclophane 3
(BHPC) (Fig. 1), including salenes, have demonstrated high induc-
tion properties (>99 ee) in 1,2-addition reactions to aldehydes.3,4
Hydroxycarbonyl [2.2]paracyclophane derivatives containing
bromine as an additional substituent at the pseudo-ortho position
with respect to the carbonyl group were prepared by Ma et al.
(Fig. 2, A) as well as its Schiff bases which, as ligands, demonstrated
high selectivity in the copper-catalyzed asymmetric Henry
reaction.5 In a continuation of our studies on the asymmetric
induction ability of different types of substituted paracyclophane
backbones6 we herein elaborate on the methods of synthesis and
the resolution of novel hydroxycarbonyl [2.2]paracyclophane
derivatives containing bromine at the pseudo-geminal position
with respect to the carbonyl group (Fig. 2, B), and showed applica-
FHPC, 1
AHPC, 2
BHPC, 3
Figure 1. ortho-Hydroxycarbonyl [2.2]paracyclophane derivatives.
O
R
O
R
C
C
OH
OH
Br
Br
A
B
R=CH3 or Ph
* Corresponding author. Tel.: +7 499 135 92 68; fax: +7 499 135 50 85.
E-mail address: nostr1@yandex.ru (N.V. Vorontsova).
Figure 2. Tris-substituted bromine-containing ortho-hydroxycarbonyl [2.2]paracy-
clophane derivatives.
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.03.038

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N. V. Vorontsova et al. / Tetrahedron: Asymmetry 21 (2010) 731–738
ded the target product 6 but the yield was low (30%). For the Br-
2. Results and discussion
AHPC 6, an X-ray diffraction study was carried out (Fig. 3).
12-Bromo-4-hydroxy[2.2]paracyclophane 4 was selected as the
starting material and was obtained from 4,12-dibromo[2.2]paracy-
clophane.7,8 We carried out several reactions of pseudo-ortho-bro-
mophenol 4 with paraformaldehyde. Earlier, FHPC 1 was obtained
by alkylation of 4-hydroxy[2.2]paracyclophane 5 with paraformal-
dehyde in the presence SnCl4 and Bu3N.9 However, it was found
that the alkylation of pseudo-ortho-bromophenol 4 does not occur
under these conditions and starting bromophenol was recovered
from the reaction mixture in quantitative yield. Increasing the
reaction time, the addition of a triple excess of alkylating reagent,
and a change of catalyst to TiCl4 did not lead to the formation of
product 1. This is probably because of a bulky bromine atom at
the pseudo-gem-position to the estimated place of attack not
allowing alkylation of bromophenol 4.
The possibility of preparing tris-substituted ortho-hydroxycar-
bonyl [2.2]paracyclophane derivatives by acylation of 12-bromo-
4-hydroxy[2.2]paracyclophane
4 with acylchloride/TiCl4 was
studied under conditions analogous to those described for 4-
hydroxy[2.2]paracyclophane (Scheme 1).10
Figure 3. General view of one independent molecule of 4-acetyl-13-bromo-5-
hydroxy[2.2]paracyclofane in the structure of 6 with the representation of atoms by
thermal ellipsoids at the 50% probability level; (O1ꢂ ꢂ ꢂO2) = 2.485(3) Å, (O1–H1–
O2) = 146°, (O10ꢂ ꢂ ꢂO20) = 2.493(3) Å, (O10–H2–O20) = 147°.
OH
OH
O
CH3COCl, TiCl4
CH2Cl2, r.t.
The standard method of preparing the enantiomers of the
hydroxycarbonyl [2.2]paracyclophane derivatives involved resolu-
tion of their racemates via diastereomeric Schiff bases with (S)-
C
CH3
phenylethylamine [(S)-
We have elaborated on the procedure of the preparation of dia-
stereomeric Schiff bases of Br-AHPC 6 with (S)- -PEA. The transfor-
a
-PEA].5,10
Br
Br
4
6
, Br-AHPC
63%
a
mation was carried out in refluxing toluene in the presence of
Et2SnCl2 as a catalyst for 43 h in nearly quantitative yield leading
to an equimolar mixture of two diastereomers, 12-bromo-4-
hydroxy-5[1-(1-phenyl-ethylimino)-ethyl]-[2.2]paracyclophane 7
(Scheme 2).
Scheme 1. The preparations of Br-AHPC 6.
The reaction of bromophenol 4 with acetyl chloride was carried
out at various temperatures. A maximum yield of 1[13-bromo-5-
hydroxy[2.2]paracyclophane-4-yl)]ethanon 6, Br-AHPC, 63%) was
achieved at 20 °C over 72 h. Our attempts to reduce the reaction
time by increasing the temperature led to a decrease in yield of
the target product. The formation of the acetylated product does
not occur in boiling CH2Cl2, and starting pseudo-ortho-bromophe-
nol 4 formed tars. Acetylation which was carried out at 30 °C affor-
The individual ketimines 7 were separated by preparative col-
umn chromatography on silica gel and then re-crystallized from
heptane, to give (Sp,S)-7 (½a D25
¼ ꢁ397:9, toluene) and (Rp,S)-7
ꢀ
(½a 2D5
¼ þ872:0, toluene) with diastereomeric purities exceeding
ꢀ
99% as determined by 1H NMR spectroscopy.
The absolute configurations of diastereomeric Schiff bases 7
were established by X-ray diffraction analysis of crystalline
OH
OH
O
CH3
c
CH3
Ph
C
N
C
CH3
Br
Br
(Rp)-6
(Rp,S)-7
a b
,
rac-6
CH3
Ph
O
C
N
C
CH3
CH3
c
OH
OH
Br
Br
(Sp,S)-7
(Sp)-6
Scheme 2. Resolution of Br-AHPC 6 into its enantiomers. Reagents and conditions: (a) (S)-a-PEA, Et2SnCl2, toluene, 110 °C; (b) chromatography resolution SiO2/CH2Cl2, than
crystallization from hexane; (c) Na2S2O5, EtOH/H2O.

N. V. Vorontsova et al. / Tetrahedron: Asymmetry 21 (2010) 731–738
733
ketimine with Rf = 0.190 (SiO2/CH2Cl2) obtained from a mixture
pentane/heptane. The configuration of this diastereomer was
determined as (Rp,S)-7 (Fig. 4), the (Sp,S)-configuration was as-
signed to diastereomer 7 with Rf = 0.093.
bonding –OHꢂ ꢂ ꢂN@, which was confirmed by X-ray investigations
of (Rp,S)-7 (Fig. 3), according to which the distance –OHꢂ ꢂ ꢂN@
1.7510 Å, –Oꢂ ꢂ ꢂN@ 2.4832 Å.
The acylation reaction of 4 with benzoyl chloride was carried
out under conditions similar to those used for the synthesis of
BHPC 3 [TiCl4 (1.3 equiv), CH2Cl2, room temperature] (Scheme 3).
Unlike the benzoylation of unsubstituted phenol 5, the same
reaction with bromophenol 4 produced a mixture of two com-
pounds, namely the ortho-regioselective C-acylated-[13-bromo-5-
hydroxy[2.2]paracyclophane-4-yl)]phenylmetanon
8
(Br-BHPC,
26%) and the O-acylated product [12-bromo[2.2]paracyclophane-
4-yl)]benzoate 9 (19%) (Table 1). The interaction time of bromo-
phenol 4 with TiCl4 was increased from 0.5 to 1.5 h. This resulted
in a decrease of yield of the side product 9 from 19% to 7%, and thus
an increase in the yield of the target Br-BHPC 8 from 26% to 53%,
and a decrease in the reaction time from 28 to 7 days (Table 1).
Table 1
Reaction of 12-bromo-4-hydroxy[2.2]paracyclophane with benzoylchloride
Run
Ratio of 4/
TiCl4/
PhC(O)Cl
Interaction time
of 4 with TiCl4
(h)
Reaction
time
(day)
Ratio
of 8/
9
Yield
of 8
(%)
Yield
of 9
(%)
1
2
1/1.3/1
1/1.3/1
0.5
1.5
28
7
1.4/1
8.1/1
26
53
19
7
The reaction of Br-BHPC 8 with (S)-a-PEA gave an equimolar
mixture of diastereomeric Schiff bases, 12-bromo-4-hydroxy-5[1-
(1-phenyl-ethylimino)-(phenyl)methylen-[2.2]paracyclophane 10
(Scheme 4). A stronger Lewis acid, TiCl4, was used as the catalyst,
and thus was efficient for the synthesis of diastereomeric Schiff
bases BHPC 3 with
quantitative in refluxing toluene after 60 h, with water being re-
a
-PEA.10 The reaction was carried out nearly
Figure 4. General view of (Rp,S)-12-bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-
ethyl]-[2.2]paracyclophane in the structure of 7 with the representation of atoms
by thermal ellipsoids at the 50% probability level; (O1ꢂ ꢂ ꢂN1) = 2.484(4) Å, (O1–H1–
N1) = 148°.
moved by a Dean–Stark trap filled with MgSO4.
For the separation of diastereomeric ketimines 10, a combined
method was used. The first stage of the procedure was based on
the different solubility of Schiff base 10 in ethanol. Single-shot
crystallization of the starting mixture gave the less soluble diaste-
reomer 10 (Rf = 0.36, CH2Cl2) in 72% yield. The following column
chromatography of the filtrate afforded both ketimines 10 in dia-
stereomerically pure forms (de >99% by NMR). Single-crystal X-
ray diffraction indicated an (Sp,S)-configuration for ketimine 10
The procedure which was used for the hydrolysis of diastereo-
meric ketimines 7 was applied using a method previously reported
for the diastereomeric Schiff bases of AHPC 2 with a
-PEA.10 Boiling
of ketimines 7 with sodium metabisulfite Na2S2O5 (3.7 eq.) in a
mixture of C2H5OH/H2O for 5 h, followed by acidification with
2 M HCl until pH 1 did not lead to the hydrolysis, and starting
Schiff bases 7 were isolated quantitatively.
with Rf = 0.36 (½a D25
¼ ꢁ549:2, toluene) (Fig. 5). Diastereomer with
ꢀ
Effective hydrolysis 7 was achieved by the addition of a twofold
excess of Na2S2O5 to a boiling solution of (Rp,S)-7 in 50% aqueous
Rf = 0.44 was given the configuration (Rp,S)-10 (½a D25
¼ þ555:0,
ꢀ
ethanol for 100 h. Enantiomer (Rp)-6 (½a D25
ꢀ
¼ þ363:3, toluene)
toluene).
The nearest analogues of the Schiff bases of Br-BHPC 10 are
those of BHPC 11. To date, no successful procedure for the hydro-
lysis of 11 has been reported.10 We were able to hydrolyze keti-
mines 11 using the technique described for the Schiff bases of
Br-AHPC 7. The hydrolysis of (Sp,S)-11 was complete after 200 h,
was obtained in 79% yield. Hydrolysis of (Sp,S)-7 gave (Sp)-6
(½a 2D5
ꢀ
¼ ꢁ361:5, toluene) with 67% yield. Since the enantiomeric
purity of the resolving agent (S)-
a
-PEA was greater than 99%, the
ee of (S)-6 and (R)-6 obtained in this way must also have been close
to this value.
The complications in the hydrolysis of ketimines 7 could be
because of the presence of strong intramolecular hydrogen
with the formation of enantiomerically pure (S)-BHPC
3
(½a 2D5
ꢀ
¼ ꢁ254:4, benzene) in 42% yield (Scheme 5).
O
OH
OH
O
O
C
PhC(O)Cl, TiCl4
Ph
C
+
CH2Cl2, r.t.
Ph
Br
Br
Br
4
8, Br-BHPC
9
Scheme 3. Acylation of 12-bromo-4-hydroxy[2.2]paracyclophane 4 with benzoyl chloride.

734
N. V. Vorontsova et al. / Tetrahedron: Asymmetry 21 (2010) 731–738
CH3
Ph
O
C
OH
Ph
C
N
Na2S2O5
Ph
CH3
Ph
Ph
C
OH
OH
EtOH/H2O
200 h
N
Br
(Sp)-3
(Sp)-BHPC
(Rp,S)-10
(Sp,S)-11
a, b
rac-8
Scheme 5. Hydrolysis of the Schiff base of BHPC 3 with (S)-a-PEA.
CH3
Ph
C
N
Ph
of 0.1 equiv of the chiral catalyst 7 or 10 in toluene at 0 °C. The
mixture was stirred at room temperature for 15 h. Excessive Et2Zn
was destroyed by adding 1 M HCl and after standard work-up (see
Section 4), the enantiomeric excess of the resulting 1-phenylpropa-
nol 12 was determined by chiral HPLC chromatography. All reac-
tions proceeded smoothly to give alcohol 12 with high
conversion ratios (>95%). Both diastereomeric pairs (Rp,S)-7,
(Sp,S)-7 and (Rp,S)-10, (Sp,S)-10 have shown high asymmetric
induction. The results displayed in Figure 5 for the sake of compar-
ison are obtained by the catalysis of this reaction with the corre-
sponding Schiff base of AHPC (Rp,S)-13, (Sp,S)-13 and BHPC
(Rp,S)-11, (Sp,S)-11.4
The Schiff bases derived from Br-BHPC demonstrated better effi-
ciency compared with those derived from Br-AHPC ((Rp,S)-10—85%
(S)-12, (Sp,S)-10—91% (S)-12; and (Rp,S)-7—77% (R)-12, (Sp,S)-7—
81% ee (S)-12, respectively). In comparison with Br-AHPC and Br-
BHPC derivatives together with the analogous Schiff bases of AHPC
and BHPC 7, 10 and 13, 11 the ketimines of Br-AHPC and AHPC dis-
play an approximately equal induction ability; however introduc-
OH
Br
(Sp,S)-10
Scheme 4. The preparations of diastereomeric Schiff bases 8 Br-BHPC with (S)-
PEA. Reagents and conditions: (a) (S)- -PEA, TiCl4, toluene, 110 °C; (b) chromatog-
raphy resolution SiO2/CH2Cl2, then crystallization from hexane.
a-
a
However, our attempts to hydrolyze the Schiff base of Br-BHPC
10 using this method were unsuccessful. The reaction did not occur
even after 200 h and starting ketimines 10 were recovered almost
quantitatively.
In our opinion the difficulties of hydrolysis of the Schiff base de-
rived from Br-BHPC 10 can be attributed to the presence of a strong
intramolecular hydrogen bond –OHꢂ ꢂ ꢂN@, which was confirmed by
X-ray diffraction investigations of (Sp,S)-10 (Fig. 5), where the dis-
tance OHꢂ ꢂ ꢂN@ 1.7478 Å, Oꢂ ꢂ ꢂN 2.5040 Å, and by the presence of a
bulky Br-substituent in a pseudo-geminal position to imino group.
The synthesized ketimines 7 and 10 were tested as chiral induc-
tors in the asymmetric addition of Et2Zn to benzaldehyde (Fig. 6).
The standard experimental procedure included the addition of
2.2 equiv of Et2Zn and 1 equivalent of benzaldehyde to a solution
ing
a bromine atom led to an inversion of the absolute
configuration of the resultant 12, whereas both Br-BHPC Schiff
bases gave an increase in enantioselectivity of 12 with the same
configuration in the case of (Rp,S)-10 and opposite configuration
for (Sp,S)-10. The best result was observed for (Sp,S)-10 (91% ee).
Figure 5. General view of (Sp,S)-12-bromo-4-hydroxy-5[(1-phenyl-ethylimino)-(phenyl)methylen]-[2.2]paracyclophane in the structure of 10 with the representation of
atoms by thermal ellipsoids at the 50% probability level; (O1ꢂ ꢂ ꢂN1) = 2.504(2) Å, (O1–H1–N1) = 149°.

N. V. Vorontsova et al. / Tetrahedron: Asymmetry 21 (2010) 731–738
735
OH
Et
Ph
H
Et2Zn
C
Ph
CHO
60
[L], 10 mol.%
12
L
(Rp)-Br-BHPC·(
S)-PEA 10
(Rp)-BHPC·( )-PEA 11
S
91
85
(Sp)-Br-BHPC·(S)-PEA 10
p)-BHPC·( )-PEA 11
(
S
S
(
(
R
R
p)-Br-AHPC·(
S
)-PEA
7
77
82
p)-AHPC·( )-PEA 13
S
(
(
S
p)-Br-AHPC·(
S
)-PEA
7
81
83
Sp)-AHPC·(
S)-PEA 13
0
20
40
60
80
100
Figure 7. Projection of molecular view for two independent molecules of 6.
Superimposed atoms are C3, C6, C11, C14 and, respectively, C60, C30, C140, C110.
e.e, %
configuration of 1-phenyl-propanol
-
or
Figure 6. Enantioselective addition of diethylzinc to benzaldehyde catalyzed by
bidentate iminophenol ligands.
(Fig. 7), thus crystalline 6 is a racemic mixture of (R)- and (S)-4-
acetyl-13-bromo-5-hydroxy[2.2]paracyclophanes.
The paracyclophane rings of 6, 7 and 10 adopt boat conformation
Comparative analysis of the results of the X-ray investigations
of compounds 6, 7 and 10 has showed some specific features of
the molecular structure of tris-substituted bromine-containing
ortho-hydroxycarbonyl [2.2]paracyclophane derivatives. The solid
state molecular structures of 6, 7 and 10 are represented in Figures
3–5 and their main geometric parameters are listed in Table 2. All
substances crystallize in chiral space groups (P1, P61 and P212121,
respectively) and contain heavy bromine atoms that allow us to
obtain the absolute configurations of 7 and 10 via the anomalous
X-ray dispersion technique. The crystals of 6 contain two symmet-
rically independent molecules which are enantiomeric forms of 6
with average atom deviation from the least-squared planes (Rms
)
equal to ca. 0.07 Å. The phenyl rings of 7 and 10 are almost planar
(Rms does not exceed 0.007(3) Å). The range of the C–C bond dis-
tances of the (C3–C4–C5–C6–C7–C8) ring of paracyclophane is
more pronounced than that of the (C11–C12–C13–C14–C15–C16)
ring (Table 2). Although C5–C17 bond is a single one, the orientation
of the substituent at the C5 atom of the paracyclophane seems
dictated by the presence of intramolecular hydrogen O–Hꢂ ꢂ ꢂO 6
and O–Hꢂ ꢂ ꢂN 7 and 10 bonds (Figs. 3–5). The planar orientation of
O1–C5–C4–C17–O2 or O1–C4–C5–C17–N1 fragment (Rms ꢃ 0.03Å)
results from this hydrogen bonding. As all acidic hydrogen atoms
are involved in intramolecular bonding only weak intermolecular
bonds (C–Hꢂ ꢂ ꢂC, C–Hꢂ ꢂ ꢂO and C–Hꢂ ꢂ ꢂBr) are present in the struc-
tures of 6, 7 and 10.
Table 2
Selected geometric parameters of molecules 6, 7 and 10 (Å)
3. Conclusion
Bond
6
7
10
0.13(H2O)
In conclusion, we have synthesized racemic Br-AHPC and Br-
BHPC and described a simple and efficient procedure for the reso-
lution of Br-AHPC into enantiomers. The application of enantiome-
C–Br
1.903(3)–
1.915(3)
1.343(4)–
1.345(4)
1.138(4)–
1.238(4)
1.901(4)
1.343(4)
1.902(1)
1.344(2)
C–O
rically pure ketimines Br-AHPC and Br-BHPC with (S)-a-PEA as
chiral ligands in asymmetric Et2Zn addition to benzaldehyde affor-
C17@O2
ded the 1-phenylpropanol having 77–91% ee. Hydrolysis condi-
tions for Schiff bases of BHPC with (S)-a-PEA 11 have been
described and BHPC was obtained in enantiomerically pure form.
C17@N1
C4–C17 (or C5–C17)
1.296(5)
1.473(5)
1.293(2)
1.481(2)
1.480(4)–
1.498(4)
1.369(5)–
1.419(5)
1.383(5)–
1.427(4)
1.571(5)–
1.585(5)
0.073(3)–
0.079(3)
0.071(3)–
0.072(3)
2.97
C3–C4, C4–C5, C5–C6, C6–C7, C7–
C8, C8–C3
C11–C12, C12–C13, C13–C14, C14–
C15, C15–C16, C16–C11
C1–C2, C9–C10
1.382(5)–
1.429(5)
1.388(5)–
1.408(5)
1.582(6)–
1.586(5)
0.070(3)
1.382(2)–
1.427(2)
1.388(2)–
1.400(2)
1.577(2)–
1.590(2)
0.071(2)
4. Experimental
4.1. General
r
r
1a
2a
Toluene was distilled from sodium ketyl benzophenone under
argon. CH2Cl2 was passed from a column filled with Al2O3. Acetyl
chloride and (S)-a-phenylethylamine were purchased from Merck
and used without purification. Benzoyl chloride was distilled under
reduced pressure. NMR: Bruker AVANCE-400 (400.13 and
100.61 MHz, for 1H and 13C, respectively); Bruker AVANCE-300
(300.13 and 75.47 MHz, for 1H and 13C, respectively); Bruker
AVANCE-600 (600.22 and 150.93 MHz, for 1H and 13C, respec-
0.077(3)
2.99
0.074(2)
2.97
da
a
r
1—average deviation of atoms from the least-squared plane (C3–C4–C5–C6–
C7–C8); 2—average deviation of atoms from the least-squared plane (C11–C12–
r
C13–C14–C15–C16); d—the distance between the centres of above-mentioned
rings.

736
N. V. Vorontsova et al. / Tetrahedron: Asymmetry 21 (2010) 731–738
tively). For 1H NMR, the residual signal of the solvent protons with
the chemical shift d 7.27 (CDCl3) was used as the internal standard.
Mass spectra were obtained on a KRATOS MS890A mass spectrom-
eter (70 eV). TLC analyses were performed on silica gel pre-coated
SORBFIL plates PTLC-A-UV (Sorbpolimer). Optical rotations were
recorded on a Perkin–Elmer 241 instrument in a thermostated cell.
Column chromatography was performed on Kieselgel 60, 230–400
mesh ASTM (Merck). Enantiomeric analyses were carried out by
HPLC on Chiralpak AD-H analytical column using hexane/2-propa-
nol (100/4) as an eluent (1 mL/min) detected at 254 nm.
H-15), 6.68 (d, 3J = 7.8 Hz; 1H, H-16), 7.11 (d, 4J = 1.8 Hz; 1H, H-
13), 7.20–7.26 (m, 1H, p-Ph); 7.29–7.35 (m, 4H, Ph); 17.26 (br s,
1H, –OH); 13C NMR (CDCl3, 300 MHz): d 21.48, 25.52, 32.36,
33.86, 34.70, 36.55, 57.55, 120.37, 124.17, 126.82, 127.08, 127.83,
129.49, 130.70, 131.63, 132.73, 134.82, 137.64, 138.16, 142.22,
143.45, 143.99, 170.28, 171.63. Anal. Calcd for C26H26BrNO: C,
69.64; H, 5.84; N, 3.12; Br, 17.82. Found: C, 69.60; H, 5.77; N,
3.08; Br, 17.94.
4.3.2. (Rp,S)-7
TLC Rf = 0.190 (eluent CH2Cl2); 0.092 g (47%); mp 99–100 °C;
4.2. rac-1[13-Bromo-5-hydroxy[2.2]paracyclophane-4-
yl)]ethanon (Br-AHPC) 6
½
a 2D5
ꢀ
¼ þ872:0 (c 0.25, toluene); 1H NMR (CDCl3, 600 MHz): d
1.66 (d, 3J = 6.7 Hz; 3H, –CH3), 2.37 (s, 3H, –CH3), 2.43–2.51 (m,
1H, –CH2–CH2–); 2.60–2.70 (m, 1H, –CH2–CH2–); 2.99–3.15 (m,
3H, –CH2–CH2–); 3.22–3.31 (m, 2H, –CH2–CH2–); 3.42–3.50 (m,
1H, –CH2–CH2–); 4.78 (q, 3J = 6.7 Hz; 1H, –CH–); 5.96 (d,
3J = 7.8 Hz; 1H, H-7 or H-8), 6.44 (d, 3J = 7.8 Hz; 1H, H-8 or H-7),
6.61 (dd, 3J = 7.8, 4J = 1.8 Hz; 1H, H-15), 6.64 (d, 3J = 7.8 Hz; 1H,
H-16), 6.94 (dd, 4J = 1.8; 1H, H-13); 7.31 (d, 3J = 7.5 Hz; 1H, p-Ph);
7.42 (t, 3J = 7.5 Hz; 2H, 2 m-Ph); 7.53 (d, 3J = 7.5 Hz; 2H, 2 o-Ph);
17.14 (br s, 1H, –OH); 13C NMR (CDCl3, 600 MHz): d 21.34, 25.34,
32.12, 33.85, 33.91, 37.04, 57.46, 120.35, 124.11, 127.05, 127.83,
128.08, 129.28, 130.36, 130.85, 133.23, 135.25, 137.91, 138.46,
142.54, 143.40, 143.51, 170.63, 170.91. Anal. Calcd for C26H26BrNO:
C, 69.64; H, 5.84; N, 3.12; Br, 17.82. Found: C, 69.82; H, 5.70; N,
3.02; Br, 17.87.
To a solution of 4 (0.50 g, 1.65 mmol) in CH2Cl2 (13 mL) was
added TiCl4 (0.23 mL, 2.13 mmol) at 0 °C. The resulting dark cher-
ry-coloured solution was stirred at room temperature for 40 min,
then acetyl chloride (0.12 mL, 1.65 mmol) was added. The reaction
mixture was stirred at room temperature for 72 h. The resulting
solution was quenched with 30 mL of H2O and stirred for 10 min.
The yellow organic layer was washed with H2O (2 ꢄ 60 mL). The
water layer was extracted with CH2Cl2 (3 ꢄ 30 mL). Organic layers
combined were dried over anhydrous Na2SO4. The crude product
was obtained after removal of the solvent in vacuo and purified
by column chromatography (SiO2, Rf = 0.40, eluent toluene) to yield
6 (0.357 g, 63%). Analytically pure 6 was obtained by crystallization
from heptane. Mp 168–170 °C; 1H NMR (CDCl3, 400 MHz): d 2.48–
2.63 (m, 1H, –CH2–CH2–), 2.66 (s, 3H, –C(O)CH3), 2.78–2.89 (m, 1H,
–CH2–CH2–), 2.99–3.10 (m, 2H, –CH2–CH2–), 3.10–3.20 (m, 1H, –
CH2–CH2–), 3.38–3.52 (m, 2H, –CH2–CH2–), 3.67–3.77 (m, 1H, –
CH2–CH2–), 6.22 (d, 3J = 7.8 Hz; 1H, H-15, or H-7, or H-8), 6.58
(dd, 3J = 7.8 Hz; 4J = 1.8 Hz, 1H, H-16), 6.61 (d, 3J = 7.8 Hz; 1H, H-
7, or H-8, or H-15), 6.64 (d, 3J = 7.8 Hz; 1H, H-8, or H-7, or H-15),
6.97 (d, 4J = 1.8 Hz; 1H, H-12), 7.27 (s, 1H, –OH); 13C NMR (CDCl3,
400 MHz): d 30.7, 31.4, 33.1, 33.6, 35.8, 120.9, 126.4, 127.9,
128.4, 130.7, 132.7, 134.7, 137.1, 140.2, 142.7, 143.3, 162.8
C(OH), 204.3 C(O); MS (EI), m/z (rel): 344 (14, [M-H]+), 265 (9,
[MꢁHꢁBr]+), 247 (7), 184 (6), 163 (6), 162 (34), 161 (100), 147
(6), 134 (12), 133 (16), 120 (15), 105 (6), 103 (9). Anal. Calcd for
C18H17BrO2: C, 62.62; H, 4.96.; Br, 23.14. Found: C, 62.89; H,
4.90; Br, 23.36.
4.4. (Rp)-Br-AHPC, (Rp)-6
To a solution of (Rp,S)-7 (0.215 g, 0.48 mmol) in EtOH (12.5 mL),
H2O (3.7 mL) and Na2S2O5 (0.334 g, 1.76 mmol) were added. The
resulting mixture was refluxed for 50 h. Then Na2S2O5 (0.334 g,
1.76 mmol) was added and the resulting suspension was diluted
with 50% aq EtOH until the reaction mixture became clear. The
solution was then refluxed for 50 h. The mixture was cooled to
room temperature and an excess of 2 M HCl was added to adjust
to pH 5–7. The mixture was extracted with toluene (3 ꢄ 20 mL),
and the organic layer was successively washed with H2O
(2 ꢄ 20 mL), saturated aq Na2CO3 (20 mL) and H2O (20 mL), and
dried with Na2SO4. After evaporation of the solvent in vacuo and
purification of the solid residue on SiO2 (eluent CHCl3), 0.111 g
(79%) of (Rp)-6 was isolated. An analytically pure sample of (Rp)-
4.3. 12-Bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-ethyl]-
[2.2]paracyclophane, (Rp,S)-7 and (Sp,S)-7
6 was obtained by recrystallization from hexane; mp 146–
148 °C; ½a 2D5
¼ þ363:3 (c 0.23, toluene). Anal. Calcd for C18H17BrO2:
ꢀ
C, 62.62; H, 4.96; Br, 23.14. Found: C, 62.81; H, 4.85; Br, 22.92. 1H
NMR data are identical to those of a racemic sample.
A solution of racemic 6 (0.150 g, 0.44 mmol) with (S)-a-PEA
(0.06 mL, 0.48 mmol) and a catalytic amount of Et2SnCl2 in 8 mL
of toluene was refluxed in an apparatus equipped with a Dean–
Stark trap filled with anhydrous MgSO4 for 43 h. A diastereomeric
mixture of ketimines 7 was obtained after removal of the solvent in
vacuo with quantitative yield. The individual diastereomers was
obtained by column chromatography (SiO2, eluent CH2Cl2). Analyt-
ically pure (Rp,S)-7 and (Sp,S)-7 were obtained by crystallization
from heptane. MS (EI), m/z (rel): 448 (10, [M]+), 447 (23,
[MꢁH]+), 266 (20), 265 (100), 264 (34), 251 (5), 250 (22), 249
(5), 248 (6), 174 (6), 162 (11), 161 (94), 160 (100), 146 (10), 132
(17), 118 (5), 117 (7), 115 (7), 105 (30), 104 (5), 103 (13).
4.5. (Sp)-Br-AHPC, (Sp)-6
Compound (Sp)-6 was obtained by the same method from
(Sp,S)-7 in 67% yield. An analytically pure sample of (Sp)-6 was ob-
tained by recrystallization from hexane; mp 146–148 °C;
½
a 2D5
ꢀ
¼ ꢁ361:5 (c 0.23, toluene). Anal. Calcd for C18H17BrO2: C,
62.62; H, 4.96.; Br, 23.14. Found: C, 62.49; H, 4.80; Br, 23.00. 1H
NMR data are identical to those of a racemic sample.
4.6. Acylation of 12-bromo-4-hydroxy-[2.2]paracyclophane 4
with benzoyl chloride
4.3.1. (Sp,S)-7
TLC Rf = 0.093 (eluent CH2Cl2); 0.100 g (51%); mp 107–109 °C;
To a solution of 4 (0.500 g, 1.65 mmol) in CH2Cl2 (13 mL) was
added TiCl4 (0.24 mL, 2.15 mmol). The resulting dark cherry-col-
oured solution was stirred at room temperature for 1.5 h; then
benzoyl chloride (0.19 mL, 1.65 mmol) was added. The reaction
mixture was stirred at room temperature for seven days. The
resulting solution was quenched with 30 mL of H2O and stirred
for 10 min. The yellow organic layer was washed with H2O
½
a 2D5
ꢀ
¼ ꢁ397:9 (c 0.33, toluene); 1H NMR (CDCl3, 300 MHz): d
1.78 (d, 3J = 6.7 Hz; 3H, –CH3), 2.32 (s, 3H, –CH3), 2.44–2.57 (m,
1H, –CH2–CH2–), 2.74–2.89 (m, 1H, –CH2–CH2–), 2.99–3.21 (m,
3H, –CH2–CH2–), 3.34–3.56 (m, 3H, –CH2–CH2–), 4.86 (q,
3J = 6.7 Hz; 1H, –CH–), 6.04 (d, 3J = 7.8 Hz; 1H, H-7 or H-8), 6.46
(d, 3J = 7.8 Hz; 1H, H-8 or H-7), 6.59 (dd, 3J = 7.8, 4J = 1.8 Hz; 1H,

N. V. Vorontsova et al. / Tetrahedron: Asymmetry 21 (2010) 731–738
737
(2 ꢄ 60 mL). The water layer was extracted with CH2Cl2
(3 ꢄ 30 mL). The combined organic layers was dried over anhy-
drous Na2SO4 and concentrated under reduced pressure to obtain
a mixture of two products: [13-bromo-5-hydroxy[2.2]paracyclo-
phane-4-yl)]phenylmetanon 8 (Br-BHPC) and [12-bromo[2.2]para-
cyclophane-4-yl)]benzoate 9. These were separated by column
chromatography on silica gel using toluene as the eluent. Analyti-
cally pure 8 and 9 were obtained by crystallization from heptane.
(d, 3J = 7.8 Hz; 1H, H-8 or H-7), 6.54–6.58 (m, 2H, H-15, H-16),
7.12 (br s, 1H, H-13), 7.06–7.15 (m, 1H, p-Ph–C@N), 7.30–7.37
(m, 1H, p-Ph), 7.37–7.54 (m, 8H, Ph), 17.54 (br s, 1H, –OH); 13C
NMR (CDCl3, 600 MHz): d 26.15 (Me), 30.78, 33.38, 33.40, 35.36,
57.88 (N–CH), 118.62 (C-6), 123.97 (C-7), 126.50 (1C, Ph), 126.73
(2C, o-Ph), 127.20 (p-Ph), 127.52 (1C, Ph–CN), 128.72 (2C, m-Ph),
128.84 (3C, PhC@N), 129.35 (o-Ph@CN), 129.47, 130.80 (C-16)
132.42 (C-13), 133.94 (C-15), 135.54, 137.26 (C-14), 138.24 (C-8),
142.50 (C-11), 143.91 (1C, PhC@N), 144.21 (C-3) 170.82 (C@N),
171.50 (C-4). Anal. Calcd for C31H28BrNO: C, 72.94; H, 5.53; N,
2.74; Br, 15.65. Found: C, 73.04; H, 5.64; N, 2.67; Br, 15.52.
4.6.1. [13-Bromo-5-hydroxy[2.2]paracyclophane-4-
yl)]phenylmetanon 8 (Br-BHPC)
TLC Rf = 0.4; 0.355 g; 53% yield; mp 140–142 °C; MS (EI), m/z
(rel): 408 (2, [M]+), 406 (1, [M), 309 (5); 224 (26, [MꢁC8H7Br]+);
223 (100, [MꢁC8H8Br]+), 209 (12); 195 (15); 181 (8); 178 (5);
167 (6); 152 (5). 1H NMR (CDCl3, 400 MHz): d 2.51–2.64 (m, 2H,
–CH2–CH2–); 2.64–2.79 (m, 2H, –CH2–CH2–); 3.05–3.21 (m, 3H, –
CH2–CH2–); 3.45–3.58 (m, 1H, –CH2–CH2–); 6.25 (d, 3J = 7.8 Hz;
1H, H-7 or H-8); 6.59–6.65 (m, 2H, H-15 or H-16); 6.69 (d,
3J = 7.8 Hz; 1H, H-7 or H-8); 7.04 (d, 4J = 1.8 Hz; 1H, H-12); 7.41–
7.48 (m, 2H, o-Ph), 7.52–7.58 (m, 1H, p-Ph), 7.67–7.74 (m, 2H, m-
Ph), 13.13 (s, 1H, –OH). 13C NMR (CDCl3): d 31.8, 33.0, 33.8, 36.3,
119.1, 125.9, 127.4, 127.6, 128.2, 128.3, 129.6 (2C), 130.4, 132.0,
132.7, 135.0, 137.5, 141.1, 141.3, 142.6, 145.1, 163.2 (C(OH)),
200.4 (C(O)). Anal. Calcd for C18H17BrO2: C, 67.82; H, 4.70; Br,
19.62. Found: C, 67.98; H, 4.98; Br, 19.54.
4.7.2. (Rp,S)-10
TLC Rf = 0.44 (eluent CH2Cl2); 0.092 g (47%); mp 176–178 °C;
½
a 2D5
ꢀ
¼ þ555:0 (c 0.20, toluene); 1H NMR (CDCl3, 600 MHz): d
1.80 (d, 3J = 6.5 Hz; 3H, –CH3), 1.93–2.02 (m, 1H, –CH2–CH2–),
2.19–2.27 (m, 1H, –CH2–CH2–), 2.49–2.56 (m, 1H, –CH2–CH2–),
2.56–2.65 (m, 1H, –CH2–CH2–), 2.97–3.07 (m, 2H, –CH2–CH2–),
3.11–3.20 (m, 1H, –CH2–CH2–), 3.45–3.56 (m, 1H, –CH2–CH2–),
4.76–4.83 (m, 1H, –CH–), 5.89 (d, 3J = 7.8 Hz; 1H, H-7 or H-8),
6.46 (d, 3J = 7.8 Hz; 1H, H-8 or H-7), 6.51 (dd, 3J = 7.8, 4J = 1.8 Hz;
2H, H-15), 6.57 (d, 3J = 7.8 Hz; 1H, H-16), 6.75 (br d, 3J = 6.0 Hz;
1H, o-Ph–C@N), 6.95 (d, 3J = 7.8 Hz; 2H, o-Ph), 7.07–7.12 (m, 1H,
p-Ph–C@N), 7.12–7.17 (m, 1H, m-Ph), 7.20 (d, 4J = 1.8 Hz; 1H, H-
13), 7.23–7.31 (m, 1H, m-Ph–C@N), 7.42–7.49 (m, 1H, o-Ph),
7.53–7.62 (m, 1H, m-Ph–C@N), 7.91 (br d, 3J = 6.0 Hz; 1H, o-Ph–
C@N), 17.30 (s, 1H, –OH); 13C NMR (CDCl3, 600 MHz): d 24.30
(1C, CH3), 31.25, 34.10. 35.05, 35.63, 57.42, 119.27, 124.76,
126.90 (2C, Ph), 127.40, 127.67, 128.42 (br s, 2C, Ph–C@N),
129.17 (2C, Ph), 129.68 (br s, 1C, Ph–C@N), 129.84 (br s, 1C, Ph–
C@N), 129.98, 130.61, 132.15, 132.86, 134.21, 136.40, 137.70,
138.57, 143.13, 144.09, 144.65, 171.52, 172.48. Anal. Calcd for
C31H28BrNO: C, 72.94; H, 5.53; N, 2.74; Br, 15.65. Found: C,
73.03; H, 5.47; N, 2.59; Br, 15.70.
4.6.2. [12-Bromo[2.2]paracyclophane-4-yl)]benzoate 9
TLC Rf = 0.3; 0.044 g, 7% yield; mp 178–180 °C; MS (EI), m/z (rel):
408 (30, [M]+), 407 (5, [M]+), 406 (33, [M]+), 400 (8), 328 (12,
[MꢁBr]+), 327 (42); 326 (5), 323 (5), 322 (21), 299 (7), 224 (28,
[MꢁC8H7Br]+), 223 (14), 222 (8), 221 (7), 207.(8), 193 (6), 185 (8),
182 (7), 180 (8), 179 (10), 178 (9), 167 (8), 165 (10), 149 (19), 139
(7), 125 (6), 121 (8), 120 (5), 111 (6), 109 (5), 106 (11), 105 (100);
1H NMR (CDCl3): d 2.69–2.80 (m, 1H, –CH2–CH2–), 2.81–2.91 (m,
1H, –CH2–CH2–), 2.92–3.01 (m, 1H, –CH2–CH2–), 3.01–3.27 (m, 4H,
–CH2–CH2–), 3.41–3.52 (m, 1H, –CH2–CH2–), 6.48–6.60 (m, 3H,
H-8 or H-16, H-7, H-15), 6.61 (d, 3J = 7.8 Hz; 1H, H-8 or H-16), 6.87
(d, 4J = 1.8 Hz; 1H, H-5 or H-13), 7.11 (d, 4J = 1.8 Hz; 1H, H-13 or
H-5), 7.56–7.64 (m, 2H, m-Ph), 7.67–7.73 (m, 1H, p-Ph), 8.30 (d,
3J = 7.8 Hz; 2H, o-Ph). Anal. Calcd for C18H17BrO2: C, 67.82; H, 4.70;
Br, 19.62. Found: C, 67.89; H, 4.58; Br, 19.55.
4.8. Hydrolysis of Schiff bases (Sp,S)-11
To a solution of (Sp,S)-11 (0.400 g, 0.93 mmol) in EtOH (30 mL),
Na2S2O5 (1.000 g, 5.26 mmol) was added. The resulting suspension
was refluxed and H2O was added until the reaction mixture be-
came clear. The solution was refluxed for 15 h. Then an additional
portion of Na2S2O5 (1.000 g, 5.26 mmol) was added and the result-
ing suspension was diluted with H2O and EtOH until it fully dis-
solved after which the solution was refluxed for 15 h. The last
procedure was repeated until the disappearance of starting
(Sp,S)-11 by TLC (11 times). The mixture was extracted with CHCl3
(3 ꢄ 100 mL), and the organic layer was dried with Na2SO4. After
evaporation of the solvent in vacuo and purification of the solid
residue on SiO2 (eluent CHCl3), 0.130 g (42%) of (Sp)-3 were iso-
lated. An analytically pure sample of (Sp)-3 was obtained by
4.7. 12-Bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-(phenyl)
methylen]-[2.2]paracyclophanes, (Rp,S)-10 and (Sp,S)-10
A solution of racemic 8 (0.247 g, 0.60 mmol), TiCl4 (0.07 mL,
0.60 mmol) and (S)-a-PEA (0.1 mL, 0.79 mmol) in toluene (10 mL)
was refluxed in a flask equipped with a Dean–Stark trap filled with
anhydrous MgSO4 for 43 h. The solvent was removed and the
resulting mixture of diastereomeric (Sp,Rc)-10 and (Rp,Rc)-10
was separated by column chromatography on silica gel using
CH2Cl2 as the eluent. Analytically pure diastereomers 10 were ob-
tained by crystallization from hexane. MS (EI), m/z (rel): 511 (33,
[M]+), 510 (14, [M]+), 509 (35, [MꢁH]+), 510 (14, [M]+), 405 (10),
328 (23, [MꢁC8H9Br]+), 327 (78), 326 (44), 312 (20, [MꢁC8H9Br–
OH]+), 224 (16), 223 (76), 222 (100), 195 (13), 194 (24), 105 (36),
103 (11).
recrystallization from heptane; mp 149.0 °C; ½a D25
ꢀ
¼ ꢁ254:4 (c
0.25, benzene); lit. for (Rp)-3: mp 151.5–152.5 °C; ½a D25
ꢀ
¼ þ250:0
(c 0.24, benzene).10 Anal. Calcd for C23H20O2: C, 84.12; H, 6.14.
Found: C, 84.22; H, 6.04. The 1H NMR data are in a good agreement
with those of rac-3.10
4.9. Enantioselective addition of diethylzinc to benzaldehyde
catalyzed by ketimines 7 and 10 typical procedure
4.7.1. (Sp,S)-10
TLC Rf = 0.36 (eluent CH2Cl2); 0.100 g (51%); mp 150–152 °C;
To a solution of the respective Schiff base (0.01 mmol) in tolu-
ene (0.28 mL), 1.1 equiv of Et2Zn in toluene (0.2 mL, 0.22 mmol)
was added in one portion at 0 °C followed by the dropwise addition
of benzaldehyde (0.1 mmol). The mixture was stirred for 15 h at
room temperature and the reaction was quenched by the addition
of HCl solution (1N, 0.45 mL), and the reaction mixture was diluted
with Et2O (2 mL) and H2O (1 mL). The organic layer was separated
½
a 2D5
ꢀ
¼ ꢁ549:2 (c 0.20, toluene); 1H NMR (CDCl3): d 1.42 (d,
3J = 6.5 Hz; 3H, –CH3), 1.92–2.01 (m, 1H, –CH2–CH2–), 2.19–2.25
(m, 1H, –CH2–CH2–); 2.43–2.61 (m, 2H, –CH2–CH2–); 2.84–2.95
(m, 1H, –CH2–CH2–); 3.00–3.09 (m, 1H, –CH2–CH2–); 3.12–3.22
(m, 1H, –CH2–CH2–); 3.49–3.58 (m, 1H, –CH2–CH2–); 4.56 (q,
3J = 6.5 Hz; 1H, –CH–); 5.90 (d, 3J = 7.3 Hz; 1H, H-7 or H-8), 6.50

738
N. V. Vorontsova et al. / Tetrahedron: Asymmetry 21 (2010) 731–738
Table 3
mated Mo Ka radiation. The structures were solved by the direct
Crystallographic data, details of data collection and structure refinement parameters
method and refined by full-matrix least squares method against
F2 of all data, using SHELXTL PLUS software.13 Non-hydrogen atoms
were found on difference Fourier maps and refined with aniso-
tropic displacement parameters. The residual peak (0.9 e Aꢁ3) in
the structure of 7 was attributed to a disordered water molecule.
The population of the water molecules was found to be a free var-
iable (FVAR instruction) and then fixed at 0.13. The positions of
H(O) atoms were found on difference Fourier maps and of H(C)
were calculated. All hydrogen atoms were included in refinement
in isotropic approximation by the riding model with the Uiso(-
H) = 1.5Ueq(Xi) for methyl groups and water molecules and the Ui-
so(H) = 1.2Ueq(Xii) for other atoms, where Ueq(C) are equivalent
thermal parameters of parent atoms. Details of data collection
and refinement parameters are given in Table 3. Crystallographic
data (excluding structure factors) for the structures in this paper
have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication numbers CCDC 769546–
769548. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 lEZ, UK [fax:
+44(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
for compounds 6, 7 0.13(H2O) and 10
6
7
10
Chemical
formula
Mr
C18H17BrO2
C26H26BrNOꢂ0.13(H2O) C31H28BrNO
345.23
450.72
Hexagonal, P61
510.45
Crystal system, Triclinic, P1
space group
Temperature 100
(K)
Orthorhombic,
P212121
100
120
a (Å)
b (Å)
c (Å)
7.8266 (7)
8.1061 (8)
12.1276 (11)
81.048 (2)
80.680 (2)
75.286 (2)
729.06 (12)
2
20.0931 (18)
20.0931 (18)
9.6513 (10)
90
90
120
3374.5 (6)
6
1.84
10.5085 (4)
10.7928 (5)
20.8067 (9)
90
90
90
2359.82 (17)
4
1.77
a
(°)
b (°)
c
(°)
V (Å3)
Z
l
(mmꢁ1
)
2.82
Crystal size
(mm)
Tmin, Tmax
No. of
0.28 ꢄ 0.19
0.37 ꢄ 0.04
0.31 ꢄ 0.25
ꢄ 0.07
ꢄ 0.03
ꢄ 0.18
0.506, 0.827
9321, 8008, 6959 25411, 4547,3992
0.890, 0.934
0.592, 0.731
41225, 6884,6651
measured,
independent
and
Acknowledgement
observed
[I > 2
reflections
Rint
No. of
reflections
No. of
parameters
qmin 0.79, ꢁ0.48
r(I)]
Financial support of this work by the Russian Foundation for
Basic Research (Project No. 10–03–00898-a) is gratefully
acknowledged.
0.018
8008
0.060
4547
0.025
6884
375
273
308
D
qmax
,
D
0.45, ꢁ0.31
ꢁ0.041 (10)
0.39, ꢁ0.27
0.001 (4)
References
(e Åꢁ3
Flack
parameter
)
0.023 (6)
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X-ray diffraction of 6, 7 and 10 data were collected at 120(2) K
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Apex II CCD 6 and 1012 diffractometers using graphite monochro-