Synthesis and structures of novel enantiopure inherently chiral calix[4]arene-derived salphen ligands and their transition-metal complexes

Article abstract of DOI:10.1016/j.tetlet.2009.07.064

Synthesis and structures of two pairs of novel enantiopure inherently chiral calix[4]arene-derived salphen ligands were described. Several Zn²⁺, Ni²⁺, and Cu²⁺ complexes of the chiral ligands were also prepared, and their

Full text of DOI:10.1016/j.tetlet.2009.07.064

Tetrahedron Letters 50 (2009) 5430–5433
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Tetrahedron Letters
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Synthesis and structures of novel enantiopure inherently chiral
calix[4]arene-derived salphen ligands and their transition-metal complexes
Zhen-Xiang Xu a,b, Zhi-Tang Huang a, Chuan-Feng Chen a,
*
a Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences,
Beijing 100190, China
b Graduate School, Chinese Academy of Sciences, Beijing 100049, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthesis and structures of two pairs of novel enantiopure inherently chiral calix[4]arene-derived
salphen ligands were described. Several Zn2+, Ni2+, and Cu2+ complexes of the chiral ligands were also pre-
pared, and their structures were characterized by NMR, IR, CD, and HRMS spectra.
Ó 2009 Published by Elsevier Ltd.
Received 6 June 2009
Revised 10 July 2009
Accepted 14 July 2009
Available online 16 July 2009
Keywords:
Inherently chiral calix[4]arene,
Salphen ligand
Transition-metal complex
Synthesis
Structure
In the past decades, significant advances have been made in the
development of chiral salen ligands and the use of their optically
pure metal complexes as asymmetric catalysts.1 Similarly, the sal-
phen (N,N-phenylene-salicylidene) ligands, which create nearly
planar, rigid NOON coordination geometry with a vacant axial
coordination sites, have also been widely studied in coordination
and supramolecular chemistry owing to the easy synthetic accessi-
bility of a large variety of different structures.2 However, synthesis
of the chiral salphen ligands still remains a significant challenge,
which thus impeded their practical applications in material science
and asymmetric catalysis.3,4
nes based on the dual functions of Boc-
L-proline auxiliary. Espe-
cially, we12 further found that Boc-
L-proline could also be used as
the chiral acylating reagent for the enantioselective acylation of
the racemic meta-nitro substituted aminocalix[4]arenes, which
thus provided us an opportunity to developing chiral salphen
ligands. Herein, we report the synthesis and structures of a class
of novel enantiopure inherently chiral calix[4]arene-based salphen
ligands and their metal complexes.
Synthesis of the salphen ligands is depicted in Scheme 1.13,14
Starting from the optical pure inherently chiral calix[4]arenes
(cS)-1a and (cR)-1b, the meta-amino substituted inherently chiral
aminocalix[4]arenes 1a0 and 1b0 were then obtained by the reduc-
tion of 1a or 1b with Raney Ni in the presence of hydrazine hy-
drate, respectively. Reaction of 1a0/1b0 with the commercially
available 3-tert-butylsalicylaldehyde or 3,5-di-tert-butylsalicylal-
dehyde in CH2Cl2 and C2H5OH at reflux temperature gave the sal-
phen ligands (cS)-2a and (cR)-2b, and (cS)-3a and (cR)-3b,
respectively, in good yields.
The two pairs of novel salphen ligands were all air-stable, and
soluble in common organic solvents. Due to the inherently chiral
calix[4]arene backbone, 1H NMR spectra of ligands 2a and 2b
showed two singlet signals for the phenol protons at the downfield
of 12.91/12.14, and 12.89/12.13 ppm, respectively, which was
probably due to the hydrogen bonding interactions between the
phenol protons and the imine nitrogen atoms. For the protons of
two imine groups, two singlet signals at 8.25 and 7.67 ppm were
Inherently chiral calixarenes5 are a class of chiral macrocyclic
compounds with their chiralities based on the asymmetric array
of achiral groups upon the three-dimensional calix-skeletons. Since
the first example6 of inherently chiral calix[4]arene reported by
Gutsche et al. in 1982, significant efforts have been devoted to
the synthesis of inherently chiral calixarenes for their unique
structures and potential applications in chiral recognition7 and
asymmetric catalysis.8 In recent years, we9 and other groups10
developed an effective resolution approach to the enantiopure
inherently chiral calixarenes by introduction of a chiral auxiliary.
More recently, we reported a more convenient approach11 to the
enantiopure meta-substituted inherently chiral aminocalix[4]are-
* Corresponding author. Tel.: +86 10 62588936; fax: +86 10 62554449.
E-mail address: cchen@iccas.ac.cn (C.-F. Chen).
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.07.064

Z.-X. Xu et al. / Tetrahedron Letters 50 (2009) 5430–5433
5431
t-Bu
t-Bu
OH
HO
HO
OH
CHO
OH
CHO
OH
N
N
N
N
t-Bu
t-Bu
t-Bu
C2H5OH/CH2Cl2
reflux, 12h
85%
C2H5OH/CH2Cl2
reflux, 12h
85%
t-Bu
O
O
O
O
O
O
O
O
NH2
H2N
R
R
2a
2b
t-Bu
t-Bu
O
O
O
O
O
O
O
O
t-Bu
CHO
t-Bu
CHO
HO
OH
OH
HO
OH
t-Bu
t-Bu
OH
t-Bu
t-Bu
t-Bu
N
N
1a (R = NO2)
1a' (R = NH2)
1b (R = NO2)
1b' (R = NH2)
Raney Ni
N2H4.H2O
Raney Ni
N2H4.H2O
t-Bu
t-Bu
N
N
C2H5OH/CH2Cl2
reflux, 7d
60%
C2H5OH/CH2Cl2
reflux, 7d
60%
t-Bu
O
O
O
O
O
O
O
O
3a
3b
Scheme 1. Synthesis of inherently chiral calix[4]arene-derived salphen ligands.
observed, meanwhile the t-Bu groups showed five distinct signals
for 2a or 2b, respectively. In the cases of (cS)-3a and (cR)-3b, sim-
ilar 1H NMR spectral features were also observed.14 Moreover, cir-
cular dichroism (CD) spectroscopy of (cS)-2a (½a D25
ꢀ
ꢁ180°)/(cR)-2b
(½a 2D5
ꢀ
+180°), and (cS)-3a (½a D25
ꢀ
ꢁ155°)/(cR)-3b (½a D25
ꢀ
+155°) showed
excellent mirror images, indicating their each inherently chirality
(Fig. 1).
We have also obtained the single crystals of (cS)-2a and (cR)-3b
suitable for X-ray diffraction by slow evaporation of their mixture
solution of CH2Cl2 and MeOH, and the single crystals of (cS)-3a
from the acetone solution.15 The crystal structures provided fur-
ther evidences for formation of the chiral salphen ligands. As
shown in Figure 2, both the macrocyclic frameworks in (cS)-3a
and (cR)-3b adopt the cone conformation of the calix[4]arene, with
dihedral angles between the opposite phenoxy rings of 3.95° and
84.72° for (cS)-3a, and 1.67° and 84.87° for (cR)-3b, respectively.
Moreover, the intramolecular hydrogen bonding interactions be-
tween the phenol protons and the imine nitrogen atoms with the
distances of 1.877 and 1.833 Å for (cS)-3a, and 1.860 and 1.814 Å
for (cR)-3b, respectively, were also found, which are consistent
with the results in solution.
With the optical pure chiral salphen ligands in hand, the syn-
thesis of their metal complexes was then carried out according to
the known procedure.3d,16 We first tested the reactions of 2a and
2b with metal acetate reagents in 1:6 (v/v) CH2Cl2/MeOH, and
found that the salphen complexes 4–6 could be synthesized in
good isolated yields (Scheme 2). However, under the same condi-
tions as described above, the metal complexes of the salphen
Figure 2. Crystal structures of (left) compound (cS)-3a and (right) compound
(cR)-3b.
ligands 3a and 3b could not be expectedly obtained probably ow-
ing to the steric effects of 3-positioned t-Bu groups in the ligands.
Formation of the metallo-salphen complexes first came from
the obvious color changes of the reaction mixture. For 4a/4b, the
color changed from yellow of the ligands to deep red, while for
5a/5b and 6a/6b, orange or gray green of the complexes could be
observed, respectively. The complexes 4–6 were further character-
ized by the IR, NMR, and HRMS spectra. Compared with the free
salphen, lower C@N stretches in the IR spectra of the complexes
were expectedly observed.14,17 In the 1H NMR spectra of complexes
4a/4b and 5a/5b, it was found that two OH proton signals were
disappeared, while the imine proton signals shifted downfield14
Figure 1. CD spectra of (left) (cS)-2a/(cR)-2b, and (right) (cS)-3a/(cR)-3b in CH2Cl2 at 25 °C; c = 2 ꢂ 10ꢁ5 M.

5432
Z.-X. Xu et al. / Tetrahedron Letters 50 (2009) 5430–5433
t-Bu
t-Bu
t-Bu
t-Bu
O
O
M2+
N
O
OH
HO
HO
OH
2+N
N
O
M
N
N
N
M(OAc)2
M(OAc)2
N
N
CH3OH/CH2Cl2
reflux
85~90%
CH3OH/CH2Cl2
reflux
85~90%
t-Bu
t-Bu
t-Bu
O
O
O
t-Bu
O
O
O
O
O
O
O
O
O
O
O
O
O
4b (M2+ = Ni2+
5b (M2+ = Zn2+
6b (M2+ = Cu2+
)
4a (M2+ = Ni2+
5a (M2+ = Zn2+
6a (M2+ = Cu2+
)
2b
2a
)
)
)
)
Scheme 2. Synthesis of the complexes.
probably due to the Lewis acidity of the metal center of the com-
plexes. The HRMS spectra14 were also measured, which provided
further evidences for formation of the complexes. For the com-
plexes 4a/4b and 5a/5b, the peaks at m/z 1167.6697/1167.6689
or 1174.6691/1174.6627 for [M+H]+ were observed. Meanwhile
the peaks at m/z 1194.6467 and 1194.6458, corresponding to
[M+Na]+, were shown for the complex 6a or 6b, respectively. More-
applications in enantioselective polymerization18 of epoxides and
lactones, and asymmetric synthesis,19 which are now in process
in our laboratory.
Acknowledgments
We thank the NNSFC (20625206), the National Basic Research
Project (2008CB617501, 2009ZX09501-018), and the Chinese
Academy of Sciences for financial support. We also thank Dr.
Hai-Bin Song at Nankai University for determining the crystal
structures.
over, it was also found that the CD spectra (Fig. 3) of (cS)-4a (½a D25
ꢀ
ꢁ223°)/(cR)-4b (½a D25
ꢀ
+223°), (cS)-5a (½a D25
ꢀ
+55°)/(cR)-5b (½a D25
ꢀ
ꢁ55°), and (cS)-6a (½a D25
ꢀ
ꢁ133°)/(cR)-6b (½a D25
ꢀ
+133°) all showed
excellent mirror images, indicating their each purity and inher-
ently chirality.
In conclusion, we have synthesized two pairs of novel optically
pure inherently chiral calix[4]arene-derived salphen ligands and
three pairs of the chiral salphen-based complexes, and also charac-
terized their structures by NMR, CD, HRMS spectra, and X-ray crys-
tallographic analyses. We believe that these novel chiral salphen
ligands and their metal complexes will be found practical
Supplementary data
Supplementary data (Synthetic procedures and characterization
data of new compounds. Copies of IR and HRMS spectra. Crystal data
of (cS)-2a, (cS)-3a, and (cR)-3b.) associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2009.07.064.
References and notes
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Z.-X. Xu et al. / Tetrahedron Letters 50 (2009) 5430–5433
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suspension of (cS)-1a/(cR)-1b (428 mg, 0.52 mmol) and a catalytic amount of
Raney Ni in THF (40 mL) was added hydrazine hydrate (2.1 mL) dropwise. After
the mixture was refluxed 2 h under argon, the Raney Ni was filtered over Hyfro
and the solvent was evaporated. The residue was taken up in CH2Cl2 (50 mL),
washed with H2O (30 mL) and brine (30 mL), dried over anhydrous Na2SO4. After
evaporation of the solvent, a white solid was obtained and dissolved in a mixture
of C2H5OH/CH2Cl2 (15:1 v/v) without any purification. The solution was refluxed
under N2 for 12 h after the addition of 2 equiv 3-tert-butylsalicylaldehyde or 3, 5-
di(tert-butyl)salicylaldehyde. The yellow precipitate was filtered off after the
removal of half of the solvent under reduced pressure.
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