C2-Symmetric chiral diamine ligands for enantiomeric recognition of amino acid esters and mandelic acid by proton nmr titration method

Article abstract of DOI:10.3906/kim-1207-58

Two novel C2 -symmetric chiral diamines containing α-phenylethyl and α-(1-naphthyl)ethyl chiral subunits were prepared with quantitative yields. Enantiomeric recognition properties of these simple structured diamine ligands towards D- and L-amino acid est

Full text of DOI:10.3906/kim-1207-58

Turk J Chem
Turkish Journal of Chemistry
(2013) 37: 374 – 382
¨
http://journals.tubitak.gov.tr/chem/
˙
c
⃝ TUBITAK
doi:10.3906/kim-1207-58
Research Article
C2 -Symmetric chiral diamine ligands for enantiomeric recognition of amino acid
esters and mandelic acid by proton NMR titration method
2
Hayriye ARAL,1 Tarık ARAL,1,∗ Mehmet C¸ OLAK,2 Berrin ZIYADANOGULLARI,
˙
˘
2
˙
˘
Recep ZIYADANOGULLARI
1Department of Chemistry, Faculty of Science and Art, Batman University, Batman, Turkey
2Department of Chemistry, Faculty of Science, Dicle University, Diyarbakır, Turkey
Received: 25.07.2012
•
Accepted: 11.03.2013
•
Published Online: 10.06.2013
•
Printed: 08.07.2013
Abstract: Two novel C2 -symmetric chiral diamines containing α-phenylethyl and α-(1-naphthyl)ethyl chiral subunits
were prepared with quantitative yields. Enantiomeric recognition properties of these simple structured diamine ligands
towards D- and L-amino acid esters and D- and L-mandelic acid were examined by the 1 H NMR titration method.
These ligands exhibited strong complexation (with Kf up to 2481 M−1) and good enantioselectivity (up to KL /KD
=
4.08) towards the mandelic acid enantiomers. The results show that simple structured and easily accessible acyclic
C2 -symmetrical compounds can also be used for enantiomeric recognition of racemic amino acids and mandelic acid in
addition to complex molecules such as crown ethers and other cyclic molecules.
Key words: Enantiomeric recognition, C2 symmetric, chiral diamines, amino acids, mandelic acid, NMR titration
1. Introduction
Amino acids and their derivatives are chiral organic molecules involved in a wide variety of biological processes.
They play an important role in the area of design and preparation of pharmaceuticals, as they are part of the
synthesis process in the production of drug intermediates and protein-based drugs. Therefore, the study of
the enantiomeric recognition of these compounds is of particular significance for understanding the interactions
between biological molecules and the design of asymmetric catalysis systems, new pharmaceutical agents, and
separation materials.1
Molecular recognition is a fundamental property of various natural systems, based on the ability of
a molecular receptor to form a complex preferentially with one of the enantiomers of a chiral molecule by
noncovalent interaction such as hydrogen bonding, electrostatic interaction, and hydrophobic interaction.2−5
Therefore, the chemical or biological activity of a compound often depends upon its stereochemistry in living
organisms. The study of synthetic model systems could contribute new perspectives for the development of
pharmaceuticals, enantioselective sensors, catalysts, and other molecular devices.6
The rational design of receptors with a chiral recognition ability for chiral amino acids and carboxylic acids
is still receiving considerable attention, although numerous chiral macrocyclic receptors have been developed for
amino acids and related compounds.7−13 In particular, C2 -symmetric ligands have been widely used in chiral
recognition and asymmetric synthesis.14,15 The C2 -symmetry is of great interest to the organic chemist as it
∗Correspondence: tarik.aral@batman.edu.tr
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ARAL et al./Turk J Chem
opens up the possibility of the parallel synthesis of multiple parts of the molecule, thus increasing the convergence
of retrosynthetic strategies.16,17 Interestingly, the number of targets found to possess such symmetry seems to
exceed that expected to arise from pure chance. A literature survey involving theoretical calculations and
comparisons of the energy of monomers, dimers, trimers, and tetramers was recently been published by Greer
and colleagues.18
C2 -symmetric enantiopure diamines are recognized as important structural elements of many biologically
active compounds and have been widely employed in asymmetric transformations including epoxidation,19
allylic substitution,20 hydrogenation reactions,21 and many other catalytic asymmetric transformations.22
Pena et al. synthesized a series of C2 -symmetrical and nonsymmetrical chiral diamines and used them as
chiral solvating agents for NMR enantiodiscrimination of chiral carboxylic acid.23 Ghosh and Masanta reported
the synthesis and photophysical behavior of an anthracene-labeled receptor bearing an amine group to use in
recognition of α-keto and hydroxy acids.24
Since the pioneering work of Cram and colleagues, numerous chiral macrocyclic and complex structured
ligands have been synthesized and studied for enantiomeric recognition of racemic compounds.25 However, the
use of acyclic and simple structured ligands as hosts for enantiomeric recognition of the racemic compounds is
limited. We report herein a practice synthesis of 2 novel simple structured C2 -symmetric chiral diamines (1, 2)
and evaluation of enantiomeric recognition properties of these ligands toward amino acid esters and mandelic
acid by 1 H NMR titration method.
2. Results and discussion
2.1. Synthesis
The simple structured and easily obtained organic compounds are very important in synthetic chemistry. In this
study, we synthesized 2 novel, easily obtained C2 -symmetric chiral diamine ligands bearing N-α-phenylethyl (1)
and N-α-(1-naphthyl)ethyl (2) chiral subunits. The host–guest interactions of these chiral ligands with chiral
amino acid methyl ester hydrochlorides and mandelic acid were characterized. Kf values for these host–guest
interactions are reported.
The syntheses of chiral diamines 1 and 2 were accomplished in 2 steps. Initially, C2 -symmetric di-
Br
OH
O
O
NH2
O
O
i
ii, iii
+
+
R
H
O
Br
C
H
CH
O
CH2
R
H2C
R
O
HN
NH
dialdehyde
1 : R = Phenyl
2.: R = 1-Naphtyl
Scheme 1. Reagents and conditions: i, CH3 CN, K2 CO3 , reflux, 15 h. ii, MeOH, reflux, 5 h. iii, MeOH, NaBH4 ,
room temperature, 2 h.
375

ARAL et al./Turk J Chem
aldehyde was prepared according to the procedure described in the literature.26 The 2 chiral amines, (R)-α-
phenylethylamine and (R)-α-(1-naphthyl)ethylamine, were used as chiral sources for synthesis of diamines 1
and 2 (Scheme 1). The reactions of the dialdehyde with the 2 chiral amines in MeOH following by treatment
of reactions mixtures with NaBH4 gave C2 -symmetric chiral diamines (1 and 2) with quantitative yields. All
compounds were characterized with 1 H NMR, 13 C NMR, IR and elemental analysis.
2.2. Enantiomeric recognition by 1 H NMR titration method
The molecular recognition can be characterized by various spectroscopic methods such as UV-Vis, NMR,
fluorescence, and IR.27,28 The NMR titration method has proven to be effective in determining the bonding
constant value for host–guest interaction. The advantages of the 1 H NMR method are that the experiment can
be carried out in a wide variety of solvents and that useful structural information can often be obtained.
To determine the equilibrium constant for the simple reaction requires knowledge of the equilibrium
concentrations of the species H, G, and H.G. When H and G are host and guest species that form an H.G
complex that is held together by weak intermolecular forces (e.g., hydrogen bonding and van der Waals forces),
the equilibrium constant is usually referred to as a binding constant or association constant to indicate that
the product has chemical characteristics that still strongly resemble the unassociated (‘free’) molecules. The
appearance of the NMR spectrum of the mixture represented by Eq. (1) would depend on Kf and on the rate
of the reaction.29
Kf = [H.G]/[H][G],
(1)
In this study, the association constants of the host–guest systems formed were calculated according to the
modified Benesi–Hildebrand equation,30 i.e. Eq. (2), the basis of the 1 H NMR spectra data using the same
methyl peak of the chiral hosts.
H + G ⇌ H · G
1/∆δ = 1/(Kf ∆δmax[Ho]) + 1/∆δmax
.
(2)
The enantiomeric recognitions for the hydrogen chloride salts of D-, L-AlaOMe; D-, L-ValOMe; and D-,
L-mandelic acid (Scheme 2) by chiral hosts 1 and 2 have been characterized by 1 H NMR titration method. In
all association experiments, 1:1 binding stoichiometry was observed. Figure 1 shows 1:1 complexation between
host 1 and mandelic acid by Job plots based on 1 H NMR shifts of methine proton’s signal of the guest. Figure 2
shows the spectroscopic changes of the 1 H NMR methylene (Ar-CH2 O-) protons signals of chiral host 1 (1 mM)
in the absence and presence of L- and D-mandelic acid (0.167–5 mM) in CDCl3 at 298 K. The experimental
data and 1 H NMR chemical shifts of the methylene signal are given in Table 1 for L-mandelic acid and host
1. Figure 3 shows a typical plot of the host–guest complexation of 1 and L-mandelic acid based on data given
Table 1. Binding constants (Kf ) were calculated using data given in Figure 3. Before adding the guest, the
methylene protons of host 1 showed a singlet at around 5.09 ppm. When the host and guest interacted in a
solution forming a 1:1 complex, this peak was shifted upfield and showed an AB system. The binding constant
of the complex was obtained using these peaks. Other guests showed similar behavior with different amounts of
chemical shifts. The estimated structures of complexes formed between hosts and guests are given in Scheme 3.
Probably, while amino acids preferred hydrogen bonding interaction in complexation, mandelic acid preferred
π −πand hydrogen bonding interaction. Thus, the greater enantioselectivity of mandelic acid may be explained
by forming a rigid structured complex between L-mandelic acid by appropriate π −πstacking interaction of the
376

ARAL et al./Turk J Chem
2 aromatic rings of the host and 1 of the guest and the hydrogen bonding interaction between amine groups of
the host and –OH groups of the guest. The shifting ArCH2 O-methylene protons show that the complexation
of the guest occurred in the cavity of the host and near these groups (ArCH2 O-). Nevertheless, we do not have
enough consistent data for precise information or stronger proposition.
Table 1. Experimental data of 1 H NMR titration of L-mandelic acid and host 1. [H]o: concentration of the host and
[G]o: concentration of the guest in each NMR tube.
[H]o (× 10−3
1.00
1.00
)
[G]o (× 10−3
0
)
1 / [G]o (× 102) δ (ppm) ∆δ (× 10−2
)
(1/[G]o) / 1000 1 / ∆δ
5.0953
0.176
0.333
0.666
1.000
2.000
3.000
4.000
5.000
59.9
30.0
15.0
10.0
5.00
3.33
2.50
2.00
5.1157
5.1268
5.1316
5.1394
5.1444
5.1625
5.1823
5.1831
2.04
3.15
3.63
4.41
4.91
6.72
8.70
6.74
5.99
3.00
1.50
1.00
0.50
0.33
0.25
0.20
49.0
31.7
27.5
22.7
20.4
14.9
11.5
14.8
1.00
1.00
1.00
1.00
1.00
1.00
1.00
O
-
O
-
O
OMe
OMe
OH
+
H3N
Cl
+
H3N
Cl
HO
Scheme 2. AlaOMe.HCl, ValOMe.HCl, and mandelic acid used as guests.
0.30
0.25
0.20
0.15
0.10
0.05
0.00
0.00
0.20
0.40
0.60
0.80
1.00
[G]o/([G]o + [H]o)
Figure 1. Job plots for mandelic acid and host 1 based on 1 H NMR shifts of guest’s methine signal. [G]o/([G]o +
[H]o) = 0.50; [H]o:[G]o = 1:1.
The binding constants (Kf ) and enantioselectivities (KL /KD) for the complexation of L-/D-guests with
the hosts (1, 2) in CDCl3 are given in Table 2. All guests form a stable complex with chiral host 1 and 2, as
shown in Table 2. The association constants of the chiral host 1 with the L- and D-enantiomers of mandelic
acid were found to be 2481.95 and 607.80, respectively. The L-form is 4.08 times more stable than the D-form
(KL /KD = 4.08). In the same way, host 2 exhibited chiral recognition toward the enantiomers of a mandelic
acid by KL /KD = 1.73. It was shown that host 1 exhibited stronger complexation and enantioselectivity than
host 2 toward mandelic acid.
377

ARAL et al./Turk J Chem
Figure 2. 1 H NMR spectral changes of chiral host 1 in the presence of D- and L-mandelic acid (methylene signal of
host 1) in CDCl3 .
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ARAL et al./Turk J Chem
y = 5.9014x + 14.647
R² = 0.95
y = mx+n
Kf = (n/m)x1000
60.00
50.00
40.00
30.00
20.00
10.00
0.00
0.00
2.00
4.00
1 / [G]o ( x 103)
6.00
8.00
Figure 3. Typical plot of 1 / ∆δ versus 1/ [G]o for the host–guest complexation of 1 and L-mandelic acid in CHCl3 .
O
O
O
O
R'
COOEt
O
H
H
N+
O
H
H
O
H
N
H
N
H
H
N
R
R
H
N
R
R
A
B
Scheme 3. General structures estimated for the complexes formed between hosts and guests (A: amino acids, B:
mandelic acid).
Table 2. Binding constants (Kf ) and enantioselectivities KL /KD for the complexation of L-/D-guests with the hosts
(1, 2) in CDCl3 .
Host
Guest
L-Val
D-Val
L-Ala
D-Ala
Kf (dm3/mol) KL/KD (KD/KL)
300.44
0.93 (1.08)
324.44
406.29
462.95
2481.9
0.88 (1.14)
1
L-Mandelic acid
D-Mandelic acid
L-Val
D-Val
L-Ala
D-Ala
L-Mandelic acid
D-Mandelic acid
4.08 (0.25)
607.80
85.520
0.43 (2.31)
197.83
421.69
470.35
199.61
0.89 (1.12)
2
1.73 (0.58)
115.50
379

ARAL et al./Turk J Chem
In the case of amino acid methyl ester guests, higher binding constants and enantioselectivities were
obtained for D-enantiomers. Host 2 exhibited enantioselectivity toward D- and L-valine methyl ester by
KD /KL = 2.33, while host 1 exhibited low enantioselectivity toward same guest (KD /KL = 1.1). Both
hosts 1 and 2 also exhibited low enantioselectivity toward L- and D-alanine methyl ester by KD /KL = 1.36
and 1.12, respectively. This result shows that the presence of the naphtho unit on the stereogenic center of
the host gives rise to enantioselectivities but decreases the complexation abilities toward amino acid methyl
esters. This may be due to the steric enhancing of the naphtho unit on the stereogenic center of host 2. In
the case of the mandelic acid guest, steric enhancing of the naphtho unit decreases both enantioselectivity and
complexation ability. This may be due to the fact that the steric repulsions of the naphtho unit are very high
for complexation with mandelic acid, which bears a phenyl unit in the stereogenic center.
These results demonstrate that the substituent on the stereogenic center plays a very important role
in the chiral recognition. It is also shown that the steric effect or repulsion between the substituent on the
stereogenic center (e.g., alkyl or aryl group) of the host and the guest has been found to be an important factor.
More steric repulsions decrease complexation but give rise to enantioselectivity when guests are amino acids,
but higher steric repulsions decrease both complexation and enantioselectivity when guests are mandelic acid.
3. Experimental
3.1. Materials and methods
All chemicals were of reagent grade unless otherwise specified. R/S 1-phenylethylamine and 1-(1-naphthyl)ethyla-
mine, D- and L-amino acid methyl ester hydrochlorides, and D- and L- mandelic acids were purchased from
Fluka or Merck. Silica gel 60 (Merck, 0.040–0.063 mm) and silica gel/TLC- cards (F254) were used for flash
column chromatography and thin layer chromatography. Melting points were determined with a Gallenkamp
Model apparatus with open capillaries. Infrared spectra were recorded on a Mattson 1000 FTIR model spec-
trometer. Elemental analyses were performed with a Carlo-Erba 1108 model apparatus. Optical rotations were
taken on a PerkinElmer 341 model polarimeter. 1 H (400 MHz) and 13 C (100 MHz) NMR spectra were recorded
on a Bruker DPX-400 High Performance Digital FT-NMR Spectrometer. The chemical shifts (d) and coupling
constants (J) are expressed in parts per million and hertz.
3.2. NMR experiments
3.2.1. Job plots
The stoichiometry of the complex between hosts 1 and 2 and the guests was determined using spectroscopic
changes of the same methine proton that is on the stereogenic center of the guest by continuous variation plot
(Job plot) according to the method described in the literature (Figure 1).31
3.2.2. NMR titrations
The host compound was dissolved in an appropriate amount of solvent and the resulting solution was evenly
distributed among 9 NMR tubes. The first tube was sealed only with the host compound. The guest solution
was added in increasing amounts to the NMR tubes so that the following solutions had relative amounts of guest
versus host compound. The concentration of the host was constant (1 mM) with the increasing concentrations
of the added guest (Table 1).
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ARAL et al./Turk J Chem
3.3. Synthesis
3.3.1. 4,4’-[benzene-1,4-diylbis(oxy)]dibenzaldehyde
This compound was prepared according to the procedure described in the literature.26 Mp: 164–165 ◦ C; 1 H
NMR (400 MHz, CDCl3 ) δ (ppm): 5.10 (s, 4H), 7.14 (s, 4H), 7.47 (d, J = 8.04 Hz, 4H), 7.85 (d, J = 8.04 Hz,
4H), 9.91 (s, 2H); 13 C NMR (100 MHz, CDCl3): 69.92, 115.17, 127.50, 130.32, 131.98, 136.02, 163.43, 190.73;
IR: m 3080, 2941, 2882, 2820, 2810, 2735, 1680, 1614, 1577, 1512, 1420, 1256, 1169, 990, 891, 822, 800, 651,
619, 561, 500; Anal. Calcd for C22 H18 O4 : C, 76.29; H, 5.24. Found: C, 76.30; H, 5.29.
3.4. (R,R)-(1-Phenylethy)-[4-(4-{4-[(1-phenylethyl amino)methyl]phenoxymethyl} -benzyloxy)
benzyl amine (1)
To a solution of dialdehyde (500 mg, 1.45 mmol) in 30 mL of EtOH was added (R)-1-phenylethylamine (375
mg, 3.1 mmol). The reaction mixture was heated at reflux for 16 h. The mixture was then cooled to room
temperature and NaBH4 (74 mg, 1.96 mmol) was added slowly. The reaction mixture was stirred for 2 h. The
EtOH was removed and 5 mL water was added to the residue. The mixture was then extracted with CH2 Cl2
(3 × 10 mL) and the organic extracts were combined, dried over MgSO4 , and evaporated in vacuo to give a
viscous oil with quantitative yield (800 mg). [α]2D0 = +5 (c 1, CHCl3); 1 H NMR (CDCl3 , 400 MHz) δ (ppm):
1.39 (d, J = 6.4 Hz, 6H), 2.16 (bs, 2H), 3.72 (d, J = 13.2 Hz, 2H), 3.82–3.88 (m, 4H), 5.09 (s, 4H), 6.99–7.03
(m, 4H), 7.27–7.47 (m, 18H); 13 C NMR (CDCl3 , 400 MHz) δ (ppm): 24.6, 47,6, 57,4, 70.0, 113.12, 120.9,
126.3, 127.0, 128.3, 128.45, 128.9, 129.1, 130.3, 137.6, 145.7, 156.9; IR (cm−1): 3333, 3061, 3026, 2962, 2924,
2864, 1600, 1492, 1452, 1370, 1287, 1235, 1116, 1049, 1018,777, 701; Anal. Calcd. for C38 H40 N2 O2 : C, 81.98;
H, 7.24; N, 5.03. Found: C, 81.55; H, 7.33; N, 4.95.
3.4.1. (R,R)-(1-(1-Naphthyl ethyl)-[4-(4-{4-[(1-(1-naphthylethyl amino)methyl] phenoxymethyl}
benzyloxy)benzyl amine (2)
To a solution of dialdehyde (500 mg, 1.45 mmol) in 30 mL of EtOH was added (R)-1-(1-naphthyl)ethylamine
(520 mg, 3.1 mmol). The reaction mixture was heated at reflux for 16 h. The mixture was then cooled to room
temperature and NaBH4 (74 mg, 1.96 mmol) was added slowly. The reaction mixture was stirred for 2 h. The
EtOH was removed and 5 mL water was added to the residue. The mixture was then extracted with CH2 Cl2
(3 × 10 mL) and the organic extracts were combined, dried over MgSO4 , and evaporated to give a viscous oil
with quantitative yield (950 mg). [α]2D0 = +45.4 (c 1, CHCl3); 1 H NMR (CDCl3 , 400 MHz) δ (ppm): 1.49 (d,
J = 6.4, 6H), 2.17 (bs, 2H), 3.78 (d, J = 12.8 Hz, 2H), 3.90 (d, J = 12.8 Hz, 2H), 4.60–4.70 (m, 2H), 5.01 (s,
4H), 6.93–6.98 (m, 4H), 7.24–7.32 (m, 8H), 7.39–7.49 (m, 6H), 7.73–7.75 (m, 4H), 7.85–7.88 (m, 2H), 8.05–8.07
(m, 2H). 13 C NMR (CDCl3 , 400 MHz) δ (ppm): 23.5, 47.6, 52.5, 69.8, 113.16, 120.9, 123.1, 125.2, 125.8, 126.3,
126.9, 127.1, 128.3, 128.9, 130.4, 131.4, 133.9, 137.4, 141.1, 156.9. IR (cm−1): 3343, 3058, 3040, 2961, 2923,
2864, 1599, 1493, 1452, 1370, 1288, 1235, 1117, 1050, 1015, 779, 753. Anal. Calcd. for C46 H44 N2 O2 : C, 84.11;
H, 6.75; N, 4.26. Found: C, 84.32; H, 6.84; N, 4.19.
4. Conclusion
We have developed 2 novel simple structured C2 -symmetric chiral diamines (1, 2) and studied their enantiomeric
recognition properties toward D- and L-amino acid methyl ester hydrochlorides and D- and L-mandelic acid
381

ARAL et al./Turk J Chem
using the 1 H NMR titration method. The highest enantioselectivity was obtained by host 1 toward L-mandelic
acid up to Kf = 2481 M−1 with KL /KD equal to 4.08. These results show that simple structured and easily
accessible acyclic C2 -symmetrical compounds can be used for enantiomeric recognition of racemic amino acids
and mandelic acids. The secondary amine groups of the ligands used in this study allow them to covalently
bond with several polymeric structures for enantioseparation of racemic compounds (especially mandelic acid).
These ligands can also be derived to several structurally complex compounds to give rise to their effect on
enantioselectivity.
References
1. Jinno, K. Ed. Chromatographic Separations Based on Molecular Recognition, VCH: Weinheim, 1996.
2. Marchi-Artzner, V.; Artzner, F.; Karthaus, O.; Shimomura, M.; Ariga, K.; Kunitake, T.; Lehn, J. M. Langmuir
1998, 14, 5164–5171.
3. Bohanon, T. M.; Caruso, P. L.; Denzinger, S.; Fink, R.; Mobius, D.; Paulus, W.; Preece, J. A.; Ringsdorf, H.;
Schollmeyer, D. Langmuir 1999, 15, 174–184.
4. Pu, L. Chem. Rev. 2004, 104, 1687–1716.
5. Hembury, G. A.; Borovkov, V. V.; Inoue, Y. Chem. Rev. 2008, 108, 1–73.
6. Lehn, J. M. Supramolecular Chemistry: Concepts and Perspectives, VCH: Weinheim, 1995.
7. Chadwick, D. J.; Cliffe, I. A.; Sutherland, I. O. J. Chem. Soc., Perkin. Trans. 1 1984, 1707–1717.
¨
8. K¨oylu¨, M. Z.; Aral, T.; Karakaplan, M.; Kocakaya, S¸. O.; Ho¸sgo¨ren, H. Turk. J. Chem. 2011, 35, 171–179.
9. Demirtas, H. N.; Bozkurt, S.; Durmaz, M.; Yilmaz, M.; Sirit, A. Tetrahedron 2009, 65, 3014–3018.
10. Fitzmaurice, R. J.; Kyne, G. M.; Douheret, D.; Kilburn, J. D. J. Chem. Soc., Perkin Trans. 1 2002, 6, 841–864.
11. Diederich, F. Angew. Chem., Int. Ed. Engl. 1988, 27, 362–386.
12. Aral, T.; Karakaplan, M. Tetrahedron Asymm. 2005, 16, 2119–2124.
13. Aydın, I.; Aral, T.; Karakaplan, M.; Ho¸sgo¨ren, H. Tetrahedron Asymm. 2009, 20, 179–183.
14. Kizirian, J. C.; Caille, J. C.; Alexakis, A. Tetrahedron Lett. 2003, 44, 8893–8895.
15. Turgut, Y.; Aral, T.; Ho¸sgo¨ren, H. Tetrahedron Asymm. 2009, 20, 2293–2298.
16. Whitesell, J. K. Chem. Rev. 1989, 89, 1581–1590.
17. Vrettrou, M.; Gray, A. A.; Brewer, A. R. E.; Barrett, A. G. M. Tetrahedron 2007, 63, 1487–1536.
18. Voloshchuk, T.; Farina, N. S.; Wauchope, O. R.; Kiprowska, M.; Haberfield, P.; Greer, A. J. Nat. Prod. 2004, 67,
1141–1146.
19. Pospil, P. J.; Carsten, D. H.; Jacobsen, E. N. Chem. Eur. J. 1996, 2, 974–980.
20. Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994, 116, 4089–4090.
21. Ohkuma, T.; Doucet, H.; Pham, T.; Mikami, K.; Korenaga, T.; Terada, M.; Noyori, R. J. Am. Chem. Soc. 1998,
120, 1086–1087.
22. Bennani, Y. L.; Hanessian, S. Chem. Rev. 1997, 97, 3161–3195.
23. Pena, C.; Gonzalez-Sabin, J.; Alfonso, I.; Rebolledo, F.; Gotor, V. Tetrahedron 2008, 64, 7709–7717.
24. Ghosh, K.; Masanta, G. Tetrahedron Lett. 2006, 47, 9233–9237.
25. Kyba, E. B.; Koga, K.; Sousa, L. R.; Siegel, M. G.; Cram, D. J. J. Am. Chem. Soc. 1973, 95, 2692–2693.
26. C¸olak, M.; Aral, T.; Ho¸sgo¨ren, H., Demirel, N. Tetrahedron Asymm. 2007, 18, 1129–1133.
27. Izatt, R. M.; Wang, T.; Hathaway, J. K.; Zhang, X. X.; Curtis, J. C.; Bradshaw, J. S.; Zhu, C. Y. J. Incl. Phenom.
Mol. Recognit. Chem. 1994, 17, 157–175.
28. Yuan, Y.; Gao, G.; Jiang, Z. L.; You, J. S.; Zhou, Z. Y.; Yuan, D. Q.; Xie, R. G. Tetrahedron 2002, 58, 8993–8899.
29. Connors, K.A. Binding Constants, Wiley: New York, 1987.
30. Fielding, L. Tetrahedron 2000, 56, 6151–6170.
31. Hirose, K. J. Incl. Phenom. Macrocycl. Chem. 2001, 39, 193–209.
382

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