Chiral dinaphthylporphyrin with C2 symmetry: Synthesis, resolution, and enantio-discrimination by single-crystal X-ray diffraction analysis

Article abstract of DOI:10.1016/j.tetlet.2014.04.067

An intrinsic chiral dinaphthylporphyrin with C₂ symmetry, namely [5,15-trans-bis(2-hydroxynaphthyl)-10-phenyl-20-(4-hydroxyphenyl)porphyrinato] zinc(II) (ZnDNP), has been designed and synthesized. The molecular structure of ZnDNP was determined

Full text of DOI:10.1016/j.tetlet.2014.04.067

Tetrahedron Letters 55 (2014) 3377–3380
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Chiral dinaphthylporphyrin with C2 symmetry: synthesis, resolution,
and enantio-discrimination by single-crystal X-ray diffraction
analysis
Liguo Yang a, Mengliang Zhu a, Yangjian Liu a, Wenxin Lu a, Yang Zhou b, Yongzhong Bian a,
⇑
a Beijing Key Laboratory for Science and Application of Functional Molecular and Crystalline Materials, Department of Chemistry, University of Science and Technology Beijing,
Beijing 100083, China
b College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
a r t i c l e i n f o
a b s t r a c t
Article history:
An intrinsic chiral dinaphthylporphyrin with C2 symmetry, namely [5,15-trans-bis(2-hydroxynaphthyl)-
10-phenyl-20-(4-hydroxyphenyl)porphyrinato]zinc(II) (ZnDNP), has been designed and synthesized. The
molecular structure of ZnDNP was determined by single crystal X-ray diffraction analysis. Resolution of
the racemic mixture was achieved with chiral HPLC technique. In particular, the stereostructures of the
Received 21 February 2014
Revised 12 April 2014
Accepted 17 April 2014
Available online 29 April 2014
enantiomers and the specific interactions between the chiral meso-dinaphthylporphyrin with L-Phe-OMe
were elucidated in the solid state by single-crystal X-ray diffraction analysis.
Keywords:
Porphyrin
Ó 2014 Elsevier Ltd. All rights reserved.
Chirality
Stereochemistry
Crystal structure
Chiral porphyrins are attractive scaffolds for chiral sensing1,2
and asymmetric catalysis3 due to their rigid frameworks and
unique spectroscopic properties.4 Generally, chiral porphyrins
were obtained by incorporating chiral substituents (extrinsic chi-
rality),5 or configuring achiral substituents alone a chiral axis of
the porphyrin ring (intrinsic chirality).6 Atropisomerism7 is one
of the typical mechanisms toward intrinsic chiral porphyrins, by
which the molecular chirality can generate as a result of hindered
rotation about a bond axis in the meso8 or b9 position. Because of
the facilities for the introduction of hydrogen-bonding donor/
acceptor and the flexibility of the dynamic rotation, chiral atropiso-
meric porphyrins play crucial roles in supramolecular chemistry,
such as molecular recognition8 and ordered molecular assembly.10
However, chiral meso-dinaphthylporphyrin derivatives remain
extremely rare, limited to the couple of examples of Ogoshi and
co-workers with octaethylporphyrin skeleton,8,11 and the stereo-
structure of this typical class of atropisomeric porphyrin has not
been discussed so far. On the other hand, detailed understanding
of the supramolecular interactions between a chiral porphyrin host
and a chiral guest molecule is informative for the design of porphy-
rin-based chirality-sensing12 and asymmetric catalysis13 systems.
Herein we report the synthesis of achiral dinaphthylporphyrin
porphyrin derivatives, namely [5,15-trans-bis(2-hydroxynaph-
thyl)-10-phenyl-20-(4-hydroxyphenyl)porphyrinato]zinc(II)
(ZnDNP). The enantiomers of ZnDNP were separated successfully,
and their absolute configurations were assigned by a direct method
of single-crystal X-ray diffraction analysis. The interactions
between the enantiomerically pure dinaphthylporphyrin mole-
cules with L-Phe-OMe were also elucidated in the solid state.
The two enantiomers of ZnDNP are shown in Figure 1. 2-
Hydroxylnaphthyl groups are introduced to two opposite meso
positions of the porphyrin core. The large steric hindrance of the
⇑
Corresponding author. Tel.: +86 10 8237 6920; fax: +86 10 6233 2462.
E-mail address: yzbian@ustb.edu.cn (Y. Bian).
Figure 1. Two enantiomers of ZnDNP.
http://dx.doi.org/10.1016/j.tetlet.2014.04.067
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

3378
L. Yang et al. / Tetrahedron Letters 55 (2014) 3377–3380
The synthesis of ZnDNP is shown in Scheme 1. The dibrominat-
ed porphyrin 1 was prepared through bromination of a trans-
AB-porphyrin16,17 with N-bromosuccinimide (NBS), which was
isolated and characterized by single-crystal X-ray diffraction
analysis (Fig. S1 and Table S1). Then, compound 2 was synthesized
through a Suzuki-Miyaura coupling reaction18 of 1 with 2-meth-
oxy-1-naphthylboronic acid, the cis-isomer (R,S-20) was removed
by silicon gel column chromatography and the trans-isomer (2)
was obtained with a yield of 35%. The alkoxy version of the chiral
dinaphthylporphyrin zinc(II) complex 2 was hydrolyzed by BBr3 to
convert to the free-base hydroxy version 3, followed by re-metala-
tion to obtain complex ZnDNP. The target compound ZnDNP and
the intermediates 1–3 were characterized by mass, NMR, and elec-
tronic absorption spectroscopies in addition to elemental analysis
(see the Supporting Information for details).
The molecular structure of racemic ZnDNP was determined by
X-ray diffraction analyses. Single crystals were obtained by slow
diffusion of hexane into a solution of ZnDNP in CHCl3/pyridine
(100:1 v/v). As shown in Figure 2, ZnDNP crystallizes in the mono-
clinic space group (P21/n) with two pairs of enantiomeric mole-
cules per unit cell. The Zn center is five-coordinated by four
pyrrole nitrogen atoms of porphyrin and one pyridine nitrogen
atom, forming the slightly distorted rectangular pyramid coordina-
tion geometry. The bond distance of Zn–N(pyridine) (2.128(5) Å) is
longer than the mean Zn–N(porphyrin) bond distance (2.076(5) Å),
which are similar to the corresponding reported values for other
pyridine-Zn-porphyrin systems.16,19 Because of the axial coordina-
tion of pyridine ligand, the Zn center deviates from the N4 mean
plane (by 0.344 Å) and points to the axial pyridine ligand.20 The
two naphthyl ring is almost perpendicular to the N4 mean plane
Scheme 1. Synthesis of ZnDNP. Reagents and conditions: (i) 2-methoxy-1-naph-
thylboronic acid, Pd(PPh3)4, K2CO3, DMF/toluene; (ii) BBr3, CH2Cl2; (iii) Zn(OAc)2,
CHCl3/MeOH.
9-hydrogen atoms and 2-hydroxy groups of the naphthyl rings
with the adjacent porphyrin b-hydrogen atoms effectively hinders
the free rotation about the naphthyl-meso carbon bonds,14 thus
producing two atropisomeric sites. In addition, the 2-hydroxy
groups can serve as hydrogen bonding donors and the Zn(II) center
as a coordination site15 for guest molecule binding. In the design of
ZnDNP, phenyl and 4-hydroxy-phenyl were introduced into the
other two opposite meso-positions, the different electron-donating
capacities and polarities between these two groups are crucial for
the chiral discrimination and resolution properties.
of porphyrin with
a dihedral angle of 86.26° and 87.87°,
respectively, as a result of the large steric hindrance effect. In addi-
tion, the neighboring molecules of ZnDNP are bound together
through hydrogen bondings of O(2-hydroxy-1-naphthyl)-HO
Figure 2. (a) X-ray crystal molecular structure of complex ZnDNP showing the 30% probability thermal ellipsoids for all non-hydrogen atoms. (b) Unit cell of complex
ZnDNP. (c) 1D supramolecular chain structure. Hydrogen atoms are omitted for clarity except for those of hydroxyl groups in (c).

L. Yang et al. / Tetrahedron Letters 55 (2014) 3377–3380
3379
Figure 3. Chromatogram of ZnDNP monitored by
a
UV detector at 425 nm
(ChiralPak IC, i.d. 10 ꢁ 250 mm, Daicel Co.; 25 °C; isopropanol/CH2Cl2/hexane
(1:50:50, v/v/v); isocratic flow rate: 2 mL/min).
(4-hydroxy-phenyl) and O(4-hydroxy-phenyl)-HO(2-hydroxy-1-
naphthyl), with distances of 1.820(9) and 1.977(9) Å, respectively,
forming one-dimensional (1D) supramolecular single-chain
structure. Here, the hydroxyl of the naphthyl, as well as that of
the phenyl, serves both as hydrogen bonding donor and acceptor.
The above observations imply that the porphyrin ZnDNP can be
a chiral receptor with multiple intermolecular interactions of
coordination and hydrogen bonding.
By using a chiral HPLC method, the complex ZnDNP has been
separated into two fractions with a 1:1 ratio as shown in Figure 3.
The two fractions with retention times of 22.68 and 27.11 min are
denoted as a and b, respectively, both show very weak circular
dichroism (CD) signals which is in accordance with previous obser-
vations for similar systems,8,16 whereas a and b fractions possess
identical electronic absorptions and NMR spectra, indicating the
successful resolution of enantiomers.
Figure 5. X-ray crystal structure of complex S,S-ZnDNPꢀ
L
-Phe-OMe. The thermal
ellipsoids are scaled to be the 30% probability level. Hydrogen atoms are omitted for
clarity except for those of hydroxyl groups.
Fortunately, after the formation of host-guest complex, suitable
crystals of bꢀ
diffusion of hexane into a chloroform solution of b and
-Phe-OMe was
L-Phe-OMe for X-ray analysis were obtained by slow
L
-Phe-
OMe in a 1:1 ratio. The absolute structure of bꢀ
L
acquired by the single crystal X-ray analysis results (Fig. 5 and
Table S1 in the Supporting Information), in which the b fraction
possesses S,S-configuration, with a convincing absolute structure
parameter of 0.02 (3).22 Hence, the a fraction should possess
R,R-configuration.
The specific supramolecular interactions between S,S-ZnDNP
To examine the supramolecular binding capability of the pure
enantiomers, association constants between host a and a pair of
and
L
-Phe-OMe have also been presented by the single-crystal X-
-Phe-OMe
ray diffraction analysis results. As shown in Figure 5,
L
binds S,S-ZnDNP by Zn—NH2 coordination (2.196 (11) Å) and
OH—O@C hydrogen bonding (2.024(17) Å) interactions. The com-
amino acid esters (
vis spectrophotometric titrations, Figures 4 and S2 (Supporting
Information). Upon adding - and -Phe-OMe to host a gradually,
the Soret absorption maxima underwent bathochromic shift from
425 to 435 nm, due to the formation of supramolecular complexes
L- and D-Phe-OMe) were determined by UV–
plex S,S-ZnDNPꢀ
L-Phe-OMe crystallizes in the monoclinic system
L
D
in a chiral space group (P1) with one molecule per unit cell. The
Zn(II) ion is also five-coordinated, forming slightly distorted rect-
angular pyramid coordination geometry. The Zn center deviates
from the N4 mean plane (by 0.306 Å) and points to the
aꢀ
L
-Phe-OMe and aꢀ
D-Phe-OMe, respectively. A sharp isosbestic
point appears at 430 nm for each titration, which verifies the 1:1
stoichiometry of host to guest and allows for determining the asso-
ciation constants (Kassoc) by applying a nonlinear curve-fitting
method.21 The Kassoc are evaluated as high as 1.9 ꢁ 104 and
L-Phe-OMe side. The bond distance of Zn–N(Phe) (2.196(11) Å) in
S,S-ZnDNPꢀ
L
-Phe-OMe is longer than that of Zn–N(Py)
(2.128(5) Å) in ZnDNPꢀPy, indicating a weakened coordination
interaction in the former.
2.7 ꢁ 104 Mꢂ1 for aꢀ
L-Phe-OMe and aꢀ
D-Phe-OMe respectively
In summary, an intrinsic chiral dinaphthylporphyrin ZnDNP has
been designed and prepared. The single crystal structure of the
racemic mixture of ZnDNP was obtained. The resolution for com-
pound ZnDNP was achieved by the chiral HPLC technique. The
absolute configurations of the pure enantiomers were assigned
(errors estimated as 5%), resulting very weak enantioselectivity
of 1.4 (Kassoc(aꢀ -Phe-OMe)/Kassoc(aꢀ -Phe-OMe)).
D
L
In order to assign the absolute configuration, we have tried to
prepare single crystals from the pure enantiomers a and b,
however, it was unsuccessful because of the poor crystallinity.
Figure 4. (a) Spectral change upon titration of a with
L
-Phe-OMe in CHCl3 at 25 °C. (b) Changes in
D
Abs at 425 nm for evaluating Kassoc. [a] = 2.0 ꢁ 10ꢂ6 M; [L]/[a] = 0–100.

3380
L. Yang et al. / Tetrahedron Letters 55 (2014) 3377–3380
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lecular interactions between the enantiomerically pure dina-
phthylporphyrin S,S-ZnDNP with L-Phe-OMe were elucidated in
the solid state.
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Financial support from the Natural Science Foundation of China,
National Ministry of Science and Technology of China (Grant No.
2012CB224801), Program for New Century Excellent Talents in
University, Fundamental Research Funds for the Central Universi-
ties, and Beijing Natural Science Foundation is gratefully
acknowledged.
Supplementary data
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