Absolute stereochemical determination of chiral carboxylates using an achiral molecular tweezer

Article abstract of DOI:10.1002/chem.201200371

A new type of molecular tweezer (1) has been synthesized for the direct determination of the absolute configuration of chiral carboxylates without analyte derivatization. Upon the addition of diamine and anionic guests, 1 exhibited shifts in its absorption spectrum with clear isosbestic points. The continuous variation method indicated that both the diamine and anionic guests form 1:1 host-guest complexes with 1 with very high binding affinity. When Boc-L-Ala (BLA) as a form of tetrabutylammonium salt was added to 1, a weak negative CD signal was observed. This weak CD signal was dramatically changed to a strong positive CD couplet upon addition of achiral 1,12-diaminododecane. Such a positive CD couplet was observed for all of the tested L-amino acid derivatives, while the D-amino acid derivatives gave the opposite signals. As a result of these unique characteristics of 1, it can be utilized as a highly sensitive probe for the absolute stereochemical determination of chiral carboxylates. Copyright

Full text of DOI:10.1002/chem.201200371

FULL PAPER
DOI: 10.1002/chem.201200371
Absolute Stereochemical Determination of Chiral Carboxylates Using an
Achiral Molecular Tweezer
Hongsik Yoon, Chi-Hwa Lee, and Woo-Dong Jang*[a]
Abstract: A new type of molecular
tweezer (1) has been synthesized for
the direct determination of the abso-
lute configuration of chiral carboxy-
lates without analyte derivatization.
Upon the addition of diamine and
anionic guests, 1 exhibited shifts in its
absorption spectrum with clear isosbes-
tic points. The continuous variation
method indicated that both the di-
host–guest complexes with 1 with very
high binding affinity. When Boc-l-Ala
(BLA) as a form of tetrabutylammoni-
um salt was added to 1, a weak nega-
tive CD signal was observed. This
weak CD signal was dramatically
changed to a strong positive CD cou-
plet upon addition of achiral 1,12-di-
AHCTUNGTRENGNaUN minododecane. Such a positive CD
couplet was observed for all of the
tested l-amino acid derivatives, while
the d-amino acid derivatives gave the
opposite signals. As a result of these
unique characteristics of 1, it can be
utilized as a highly sensitive probe for
the absolute stereochemical determina-
tion of chiral carboxylates.
Keywords: chirality
·
circular
dichroism · host–guest systems ·
molecular tweezer · porphyrinoids
ACHTUNGTRENNUNGamine and anionic guests form 1:1
Introduction
However, this potentially powerful approach suffers from a
severe limitation that precludes its current use in high-
throughput screening or other real-time analyses. Specifical-
ly, derivatization is required in the case of substrates bearing
only a single ligation site.[5] Herein, we present a solution to
this problem that is based on the combination of a porphyr-
in tweezer system with remote guest-binding receptor mod-
ules. In general, the chirality of the guest molecule is direct-
ly transferred to the achiral porphyrin tweezer in the form
of a twisted conformation through bidentate metal coordina-
tion. Owing to the significantly large extinction coefficient
of porphyrin units in the visible range, the conformational
twist of the porphyrin tweezer system results in large signal
amplification.[6] However, tedious derivatizations of mono-
Determination of absolute configuration remains a very im-
portant topic in chemistry because many bioactive mole-
cules are only effective if they have a specific stereo-config-
uration.[1] To date, various techniques have been developed
for the determination of absolute configuration in chiral
compounds, including optical rotation, circular dichroism
(CD), nuclear magnetic resonance, chiral chromatography,
and X-ray crystallography.[2] Among the various methods,
one of the most powerful tools for determining absolute
configuration is CD spectroscopy, in which enantiomers give
spectroscopic data with differential absorption of either left-
or right-circularly polarized light.[3] To obtain reliable CD
signals, molecules should have an appropriate chromophore
with a strong absorption. Recently, several porphyrin tweez-
er systems as probes for absolute stereochemical determina-
tion have been developed based on exciton-coupled circular
dichroism (ECCD).[4] The binding of a chiral guest to the
porphyrin tweezer induces a chiral twist of the two porphyr-
in units to minimize steric repulsion. The ECCD method
has been successfully applied to a wide variety of com-
pounds, including chiral alcohols, amines, amino alcohols,
amino acid derivatives, and bifunctional amide conjugates.
AHCTUNGTREGaNNNU mines or monocarboxylic acids tend to decrease their ap-
plicability in chiral sensing. Furthermore, a large excess of
these guest molecules is often needed to elicit a reliable CD
signal due to their weak binding affinities. Because most
naturally occurring chiral compounds can only be isolated in
very small quantities, stereochemical determination without
derivatization as well as probes with high binding affinity
would be highly desirable. To this end, we have introduced
two urea groups in a porphyrin tweezer system as remote
guest-binding modules, which provided significantly high
binding affinity for chiral carboxylates without derivatiza-
tion. Although the ECCD signal of the tweezer system man-
ifested upon chiral carboxylate binding was relatively weak,
great signal amplification was achieved upon additional
binding of an achiral diamine guest to the porphyrin units.
[a] H. Yoon, C.-H. Lee, Prof. W.-D. Jang
Department of Chemistry
College of Science
Yonsei University
50 Yonsei-ro
Seodaemun-gu, Seoul, 120-749 (Korea)
Fax : (+82)2-364-7050
E-mail: wdjang@yonsei.ac.kr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201200371.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

Results and Discussion
quent removal of the trimethylsilyl group gave 8. Finally, di-
merization of 8 yielded 1, which was unambiguously charac-
1
The synthesis of the molecular tweezer (1) is outlined in
Scheme 1. Briefly, iodination of tert-butyl aniline (2) afford-
ed 3, which was reacted with trimethylsilylacetylene to give
4. The amine group in 4 was converted into an isocyanate
group using triphosgene in CH2Cl2, and then the isocyanate
was further reacted with the amino-porphyrin (7) to gener-
ate the urea-bearing porphyrin derivative (8). The amino-
porphyrin was synthesized from 5, 6, and dipyrrolomethane
by an acid-catalyzed cross-condensation reaction and subse-
quent deprotection of the acetyl group. Metallation of the
terized by H and 13C NMR and MALDI-TOF-MS analyses.
Compound 1 exhibited Soret absorption at 419 nm with a
remarkably strong shoulder at 409 nm (Figure 1), at which
the extinction coefficient in CH2Cl2 for the Soret band was
determined to be 5.42ꢁ105 mÀ1 cmÀ1. The absorption spec-
trum of the monomeric porphyrin (8) was also measured
and featured a single sharp Soret absorption at 409 nm that
was coincident with the position of the shoulder. Since the
monomeric porphyrin absorbs at the same position as the
shoulder of 1, the major absorption of 1 at 419 nm is proba-
bly caused by exciton coupling of the two porphyrin units.[7]
Because an amine group can
porphyrin was accomplished with ZnACTHNUTRGENUG(N OAc)2, and subse-
bind to the Lewis acidic zinc
porphyrin as an axial ligand,[8]
we expected that 1 could ac-
commodate diamine guests. As
shown in Figure 2a, the addi-
tion of 1,12-diaminododecane
(DAD) to 1 resulted in a hypso-
chromic shift of the absorption
maximum from 419 to 418.5 nm
with clear isosbestic points at
379, 414, 511, 545, and 575 nm.
The bandwidth of the Soret ab-
sorption band was also reduced
along with disappearance of the
shoulder after formation of the
host–guest complex. The con-
tinuous variation method indi-
cated that 1 and DAD formed a
1:1 host–guest complex with a
very high binding affinity, the
association constant for which
was determined to be 1.2ꢁ
107 mÀ1 through
a
nonlinear
curve-fitting method using hyp-
spec software. Because axial li-
gation by the amine increases
the electron density of the zinc
porphyrin, the absorption bands
should exhibit a bathochromic
shift. However, after complexa-
tion of DAD, 1 exhibited a hyp-
sochromic shift of the absorp-
tion maximum but a bathochro-
mic shift in the position of the
shoulder. This spectroscopic
change indicated that the two
porphyrin units in 1 partially
engage in the formation of
a
slipped-cofacial structure
through p–p interaction, which
was diminished upon insertion
of DAD between them.[8]
Scheme 1. Synthesis of 1. Reagents and conditions: a) I2, Ag2SO4, EtOH, 258C, 2 h; b) trimethylsilylacetylene,
CuI, [Pd(PPh3)2Cl2], Et3N, 25 8C, 12 h; c) triphosgene, Et3N, CH2Cl2, 08C, 2 h; d) dipyrromethane, TFA,
CH2Cl2/MeOH, 258C, 12 h; e) p-chloranil, 258C, 4 h; f) HCl, EtOH, reflux, 2 h; g) 7, reflux, 12 h; h) Zn(OAc)2,
CH2Cl2/MeOH, 258C, 12 h; i) TBAF, THF, 258C, 30 min; j) Cu(OAc)2·H2O, pyridine, 258C, 12 h.
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
&
2
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

A Molecular Tweezer for Determining Stereochemistry
FULL PAPER
Figure 1. UV/Vis absorption spectra of a) 1 (solid line) and b) 8 (broken
line) in CD2Cl2 at 258C.
Meanwhile, the two urea moieties in 1 provide strong hy-
drogen-bond donor groups for binding anionic guest mole-
cules.[9] In fact, upon the addition of several different anion-
ic guests, 1 exhibited a remarkably strong spectral shift with
peak broadening, indicating a strong interaction between its
two porphyrin units after anion binding (Figure 2b). The ex-
istence of clear isosbestic points and the result of the contin-
uous variation method (Figure 2; Jobꢂs plot) indicated the
formation of a very stable host–guest complex with a 1:1
binding stoichiometry, with the association constant for
BLA exceeding 108 mÀ1.
As mentioned above, the UV/Vis absorption spectrum of
1 is indicative of an interaction between the two porphyrin
units of the tweezer. Variable-temperature (VT)-NMR and
temperature-dependent UV/Vis absorption studies of 1 in
C2D2Cl4 were carried out to obtain further information on
the initial conformation (Figure S1 in the Supporting Infor-
mation). In the VT-NMR study, all peaks became sharp
upon increasing the temperature, indicating rapid conforma-
tional interchange at high temperature. In contrast, all peaks
disappeared on lowering the temperature due to poor solu-
bility, with 1 precipitating from C2D2Cl4 solution at low tem-
perature. Although the VT-NMR experiments indicated
slight downfield shifts of all peaks, the information provided
was insufficient to confirm the initial conformation of 1.
1
Therefore, the H NMR spectrum of 8 was compared with
Figure 2. UV/Vis spectroscopic titration of 1 with DAD and BLA in
CH2Cl2 at 258C. Lower left and right graphs are binding isotherm and
Jobꢂs plot, respectively. a) [DAD]/[1]=0–3.0, [1]=2.15ꢁ10À6 m, DAbs was
monitored at 408 nm, b) [BLA]/[1]=0–3.0, [1]=2.15ꢁ10À6 m, DAbs was
monitored at 420 nm.
that of 1 (Figure 3). The signals of the pyrrolic and meso
protons of 1 were seen to be located further upfield than
those of 8, indicating a partial overlapping of the porphyrin
rings such that they were mutually affected by their respec-
tive ring currents. A UV/Vis absorption study in C2D2Cl4
also indicated partial overlapping of the porphyrin rings
(Figure S2 in the Supporting Information). The absorption
spectrum of 1 in C2D2Cl4 showed similar spectral shape to
that in CH2Cl2, with the Soret absorption at 421 nm and a
remarkably strong shoulder at 411 nm. The absorption in-
tensity at 421 nm was gradually decreased on increasing the
temperature, indicating a higher proportion of the trans-con-
formation at high temperature.
tion of Boc-l-alanine (BLA) as the tetrabutylammonium
salt, the urea NH signals exhibited a significant downfield
shift, indicating the formation of strong hydrogen bonds be-
tween the carboxylate anion and the NH protons (Figure 3).
At the same time, the signals of the pyrrole b and meso pro-
tons of the porphyrin were remarkably upfield shifted upon
the addition of BLA. This strong upfield shift can be ex-
plained in terms of p–p interaction between the two por-
phyrin units. Due to the partial overlapping of the porphyrin
1
On the other hand, H NMR study clearly showed spec-
tral changes upon the addition of anionic guests. Upon addi-
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

W.-D. Jang et al.
Figure 3. Partial 1H NMR spectra of a) 8, b) 1, c) 1ꢀBLA, and
d) 1ꢀBLA·DAD in CD2Cl2 at 258C.
units by p–p interaction, the pyrrole b and meso protons
were greatly influenced by the porphyrin ring-current effect.
When both BLA and DAD were added to 1, the degree of
upfield shift of the pyrrole b and meso proton signals was
greatly decreased. The distance between the two porphyrin
units was increased by the insertion of DAD, and hence the
influence of their ring-current effects was greatly decreased.
In sharp contrast to the proton signals corresponding to the
porphyrin units, the chemical shift of the urea NH protons
was not changed by the addition of DAD, indicating that
the urea groups maintained their hydrogen bonds.
Figure 4. UV/Vis spectroscopic titration of 1 with DAD and BLA in
CH2Cl2 at 258C in the presence of 1 equivalent BLA and DAD, respec-
tively. Lower left and right graphs are binding isotherm and Jobꢂs plot,
respectively. a) [BLA]/ACHTGNUTRENNUNG
was monitored at 420 nm, b) [DAD]/
G
10À6 m, DAbs was monitored at 402 nm.
trated with BLA in the presence of one equivalent of DAD,
the Soret absorption was slightly broadened with clear isos-
In the presence of one equivalent of BLA, 1 was again ti-
trated with DAD. In this experiment, the absorption spec-
trum exhibited a bathochromic shift with clear isosbestic
points at 441, 444, 516, and 540 nm (Figure 4a). The band-
width of the Soret absorption also narrowed. When 1 was ti-
ACHTUNGTRENbNUGN estic points at 412, 429, and 559 nm, indicating simultane-
ous accommodation of the anion and diamine guests within
1 (Figure 4b). The results of the continuous variation
method indicated the formation of 1:1 host–guest complexes
for both the diamine and anionic guests.
&
4
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

A Molecular Tweezer for Determining Stereochemistry
FULL PAPER
Because 1 exhibited strong binding affinities towards both
the diamine and anionic guests, the binding of chiral guests
induced a conformational change of the host compound,
which in turn generated ECCD signals. Therefore, CD spec-
tra of 1 were measured at 208C upon the addition of several
chiral amino acid derivatives. While 1 showed essentially no
observable CD signals, a very weak negative CD signal ap-
peared around the Soret region after the addition of three
equivalents of BLA (Figure 5). Conversely, 1 exhibited a
ured after the addition of three equivalents of DAD. Very
interestingly, the weak induced CD signals observed with
BLA were converted into a strong positive couplet after the
addition of DAD (Figure 5). Based on this information, we
re-evaluated the CD signal amplification of 1 upon the addi-
tion of several other amino acid derivatives. All of the
tested l-amino acid derivatives gave rise to a positive CD
couplet, while d-amino acid derivatives gave the opposite
signals. Furthermore, the intensities of the CD couplet were
sufficiently strong to identify the absolute stereo-configura-
tions (Table 1). Because 1 exhibited a significant and useful
Table 1. CD amplitudes of 1 induced by the binding of carboxylates in
the presence of 3 equiv DAD at 208C in a 1 cm optical cell.[a]
[b]
Guests
BDA
Asymmetry
1st/nm [De]
2nd/nm [De]
ACD
R
427.2
G
419.2
ACHTUNGTRENNUNG
À58.2
BLA
S
R
S
R
S
S
S
S
S
S
+61.4
À98.5
G
ACHTUNGTRENNUNG
Boc-d-Leu
Boc-l-Leu
Boc-d-Phe
Boc-l-Phe
Boc-l-Pro
Boc-l-Ser
Boc-l-Thr
Boc-l-Val
Mandelate
E
ACHTUNGTRENNUNG
+102.3
À135.2
+136.1
+138.2
+14.7
+61.8
+99.7
+72.3
E
ACHTUNGTRENNUNG
T
ACHTUNGTRENNUNG
E
ACHTUNGTRENNUNG
E
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
T
ACHTUNGTRENNUNG
Figure 5. CD spectra of 1 in CH2Cl2 in the presence of three equivalents
of BLA or BDA, with or without DAD (scan number 8, scan speed
200 nmminÀ1, 293 K, bandwidth=1nm, [1]=1.69ꢁ10À6 m).
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
[a] Solvent: CH2Cl2, scan speed: 200 nmminÀ1, scan number: 8, [1]=
1.69ꢁ10À6 m, [carboxylates]=5.07ꢁ10À6 m, [b] LmolÀ1 cmÀ1
weak positive CD signal upon the addition of Boc-d-alanine
(BDA) as the tetrabutylammonium salt. For many other
amino acid derivatives, very weak induced CD signals ap-
peared. Although induced CD signals appeared after the ad-
dition of chiral amino acid derivatives, the intensity of these
signals was very weak and their signs were not perfectly cor-
related with the chirality of guest molecules. The low inten-
sity of the induced CD signal upon carboxylate binding to 1
might be explained in terms of the formation of a slipped-
cofacial structure due to the strong p–p interaction between
the two porphyrin units. In addition, the binding of anionic
guests at the remote site away from the porphyrin units will
not cause strong ECCD signals
.
CD signal response upon the addition of amino acid deriva-
tives together with achiral DAD, computer-aided molecular
modeling studies were carried out using the MM3 force-
field to study the possible underlying conformational
changes.[10] Depending on the initial conformation, the
energy-minimized structure of 1 exhibited both cis- and
trans-conformers (Figure 6a and Scheme 2). A slipped-cofa-
cial structure of the two porphyrin units could be observed
at the Soret band.
Because the strong interac-
tion between the two porphyrin
units in 1 was diminished by the
insertion of DAD, we speculat-
ed that
a
conformational
change of the porphyrin units
might be enhanced by the addi-
tion of this diamine. Therefore,
CD spectra were again meas- Figure 6. Energy-minimized structures of a) 1, b) 1ꢀBLA, and c) 1ꢀBLA·DAD with omission of alkyl chains.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!

W.-D. Jang et al.
Figure 7. Twist of urea groups by the formation of multiple hydrogen
bonding with carboxylate.
strong ECCD signals become observable upon the addition
of DAD to a chiral carboxylate complex of 1. In this proc-
ess, the size and rigidity of the side groups of chiral amino
acids greatly influence the intensity of the CD signals, with
the order of signal intensity being as follows: ProꢁPhe>
LeuꢁVal >Thr ꢁAla>Ser. The ECCD is induced by a
structural twist of the two porphyrin units to minimize steric
interaction, and bulky and rigid side groups will induce
more twisted structures than smaller ones. The relative in-
tensities of ECCD upon additions of Phe, Leu, Val, and Ala
clearly reflect the influences of the side groups.
Scheme 2. Proposed mechanism of CD enhancement of 1 by the binding
of guests.
in the cis-conformation, which is consistent with the obser-
vations based on the electronic absorption spectra. Accord-
ingly, upon formation of the BLA adduct with 1 (1ꢀBLA),
1 adopted the cis-conformation through the formation of
multiple hydrogen bonds (Figure 6b). In this state, the two
porphyrin units are spatially very close to each other due to
their p–p interaction. More importantly, the directions of
the transition dipole moments for the two porphyrin rings,
which run from the 5- to the 15-position of the porphyrin
units, become almost parallel in the 1ꢀBLA complex. This
could be the reason for the generation of weak ECCD sig-
nals upon the addition of BLA to 1. Considering the addi-
tion of DAD to 1ꢀBLA, the angle between the transition
dipole moments of the two porphyrin units becomes much
greater following insertion of the diamine. Therefore, the
molecular chirality of the carboxylate may strongly induce
either a right-handed or left-handed twist to the structure of
1. In fact, the angle between the transition dipole moments
of the two porphyrin units in the energy-minimized structure
of 1ꢀBLA·DAD was much wider than that in 1ꢀBLA,
which presumably gave rise to the strong ECCD signals
(Figure 6c). The process of chiral recognition can be sum-
marized as shown in Scheme 2. The porphyrin tweezer
adopts a cis-conformation by carboxylate inclusion due to
the formation of multiple hydrogen bonds. In this process,
the two urea groups are twisted in different directions de-
pending on the chirality of the amino acid derivatives in
order to minimize steric repulsion (Figure 7). Because of the
chiral twist of the urea groups, 1 should exhibit ECCD sig-
nals. However, the electronic absorption of the urea groups
lies in the invisible UV range. Moreover, the two porphyrin
units in 1 form a slipped-cofacial structure due to the strong
p–p interaction. Therefore, 1 exhibits only weak CD signals
due to the parallel orientation of transition dipoles. On the
other hand, the chiral distortion of the urea groups is trans-
ferred to the two porphyrin units by the insertion of DAD,
because the strong p–p interaction is diminished. Therefore,
Conclusion
We have synthesized a new type of porphyrin-based molecu-
lar tweezer with two urea groups, which exhibits strong
ECCD signals upon the simultaneous complexation of chiral
carboxylate and achiral diamine guests. Because the two
urea groups and porphyrin units exhibit significantly strong
binding affinities towards chiral carboxylate and diamine
guests, respectively, the molecular tweezer can be successful-
ly utilized as a highly sensitive probe for the absolute stereo-
chemical determination of chiral carboxylates. Unlike other
porphyrin-based molecular tweezers, monodentate carboxy-
lates can be directly utilized without derivatization to deter-
mine their molecular chirality. Therefore, the concept dem-
onstrated herein provides a new strategy for the design of
efficient chiral probes.
Experimental Section
Measurements: Electronic absorption spectra were recorded on
a
JASCO model V-660 spectrometer. CD spectra were recorded on a
JASCO model J-815 spectrometer at 208C in CH2Cl2 (scan speed:
200 nmminÀ1, scan number: 8, bandwidth: 5 nm). 1H and 13C NMR spec-
tra were recorded on Bruker Advance DPX250 and DPX400 spectrome-
ters at 258C in CD2Cl2 or CDCl3. MALDI-TOF-MS was performed on
an Applied Biosystems 4700 proteomics analyzer with a-cyano-4-hydrox-
ycinnamic acid as the matrix.
Synthesis of 3:[11] I2 (3.57 g, 14.07 mmol) and Ag2SO4 (4.39 g, 14.07 mmol)
were added to a solution of 4-tert-butylaniline (2.00 g, 13.4 mmol) in
&
6
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

A Molecular Tweezer for Determining Stereochemistry
FULL PAPER
EtOH (50 mL) and the mixture was stirred for 2 h at 258C and then fil-
tered through Celite. The filtrate was concentrated and the residue was
purified by column chromatography on silica eluting with CH2Cl2/hexane
(1:3) to give 3 (1.1 g, 30%). 1H NMR (250 MHz, CDCl3, 258C): d=7.62
(s, 1H), 7.19–7.16 (d, J=8 Hz, 1H), 6.72–6.69 (d, J=8 Hz, 1H), 3.96 (s,
2H), 1.26 ppm (s, 9H).
32.18, 31.28, 30.08, 29.82, 29.78, 29.61, 26.50, 23.00, 14.21 ppm; MALDI-
TOF-MS: m/z: calcd for C132H96N12O8Zn2: 1991.23 [M+]; found: 1990.16.
Acknowledgements
Synthesis of 4:[11] 3 (1.05 g, 3.81 mmol), CuI (36 mg, 0.19 mmol), and [Pd-
ACHTUNGTRENNUNG
This work was supported by a grant from the National Research Founda-
tion (NRF) of Korea funded by the Korean government (MEST) (no.
2011-0001126). H. Yoon and C.-H. Lee acknowledge fellowships from the
BK21 program of the Ministry of Education, Science and Technology,
Korea.
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
was stirred for 16 h at 508C and then filtered through Celite. The filtrate
was concentrated and then purified by column chromatography on silica
eluting with CH2Cl2/hexane (1:5) to give 4 (0.80 g, 86%). 1H NMR
(250 MHz, CDCl3, 258C): d=7.30 (s, 1H), 7.18–7.15 (d, J=8 Hz, 1H),
6.66–6.63 (d, J=8 Hz, 1H), 4.11 (s, 2H), 1.26 (s, 9H), 0.27 ppm (s, 9H).
[1] a) P. Metola, E. V. Anslyn, T. D. James, S. D. Bull, Chem. Sci. 2012,
3, 156–161; b) L. A. Joyce, M. S. Maynor, J. M. Dragna, G. M.
da Cruz, V. M. Lynch, J. W. Canary, E. V. Anslyn, J. Am. Chem. Soc.
2011, 133, 13746–13752; c) D. Leung, S. O. Kang, E. V. Anslyn,
Chem. Soc. Rev. 2012, 41, 448–479; d) X.-C. Li, D. Ferreira, Y.
Ding, Curr. Org. Chem. 2010, 14, 1678–1697.
[2] a) K. Claborn, C. Isborn, W. Kaminsky, B. Kahr, Angew. Chem.
2008, 120, 5790–5801; Angew. Chem. Int. Ed. 2008, 47, 5706–5717;
b) S. Allenmark, Chirality 2003, 15, 409–422; c) D. Parker, Chem.
Rev. 1991, 91, 1441–1457; d) T. J. Wenzel, J. D. Wilcox, Chirality
2003, 15, 256–270; e) Y. Okamoto, E. Yashima, Angew. Chem. 1998,
110, 1072–1095; Angew. Chem. Int. Ed. 1998, 37, 1020–1043; f) T.
Ikai, Y. Okamoto, Chem. Rev. 2009, 109, 6077–6101; g) H. D. Flack,
G. Bernardinelli, Chirality 2008, 20, 681–690.
Synthesis of 7:[6b] TFA (2 mL, 26.12 mmol) was added to a solution of 5
(1.23 g, 7.51 mmol), 6 (2.72 g, 7.51 mmol), and dipyrromethane (2.20 g,
15.03 mmol) in CH2Cl2 (830 mL) and MeOH (170 mL), and the mixture
was stirred for 12 h at 258C. Thereafter, p-chloranil (8.49 g, 34.2 mmol)
was added and the reaction mixture was stirred for a further 4 h. It was
then concentrated to a volume of 200 mL and chromatographed on silica
gel eluting with 20% EtOAc/CH2Cl2. Without further purification, the
product was dissolved in a mixture of EtOH (40 mL) and aqueous HCl
(60 mL) and the solution was refluxed for 12 h. The reaction mixture was
purified by column chromatography on silica, eluting with CH2Cl2, and
the eluate was concentrated to dryness. The residue was recrystallized
from CH2Cl2/hexane to give 7 as a reddish-purple powder (0.44 g, 8%).
1H NMR (250 MHz, CDCl3, 258C): d=10.29 (s, 2H), 9.40–9.37 (m, 4H),
9.20–9.16 (m, 4H), 8.08–8.05 (d, J=8 Hz, 2H), 7.43 (s, 2H), 7.14–7.11 (d,
J=8 Hz, 2H), 6.92 (s, 1H), 4.18–4.13 (t, J=6.5 Hz, 4H), 4.06 (s, 2H),
1.92–1.86 (m, 4H), 1.53–1.28 (m, 10H), 0.90–0.85 (t, J=6 Hz, 6H),
À3.08 ppm (brs, 2H); MALDI-TOF-MS: m/z: calcd for C48H55N5O2:
733.98 [M+]; found: 736.61.
[3] a) G. Tarczay, G. Magyarfalvi, E. Vass, Angew. Chem. 2006, 118,
1807–1809; Angew. Chem. Int. Ed. 2006, 45, 1775–1777; b) S. Nieto,
V. M. Lynch, E. V. Anslyn, H. Kim, J. Chin, J. Am. Chem. Soc. 2008,
130, 9232–9233; c) X. Peng, N. Komatsu, T. Kimura, A. Osuka, J.
Am. Chem. Soc. 2007, 129, 15947–15953.
[4] a) Q. Yang, C. Olmsted, B. Borhan, Org. Lett. 2002, 4, 3423–3426;
b) X. Li, B. Borhan, J. Am. Chem. Soc. 2008, 130, 16126–16127;
c) M. Anderson, K. Wilcox, M. Guericke, H. Chu, M. V. Wilson, E.
Wilson, K. Lucas, A. E. Holmes, Chirality 2010, 22, 398–402; d) J.-
K. Choi, G. Sargsyan, M. Shabbir-Hussain, A. E. Holmes, M. Balaz,
J. Phys. Chem. B 2011, 115, 10182–10188; e) M. Tanasova, C. Vasi-
leiou, O. O. Olumolade, B. Borhan, Chirality 2009, 21, 374–382;
f) B. I. Morinaka, T. F. Molinski, Chirality 2008, 20, 1066–1070;
g) D. Das, Z. Dai, A. E. Holmes, J. W. Canary, Chirality 2008, 20,
585–591; h) V. V. Borovkov, J. M. Lintuluoto, Y. Inoue, Org. Lett.
2000, 2, 1565–1568; i) G. Proni, G. Pescitelli, X. Huang, K. Naka-
nishi, N. Berova, J. Am. Chem. Soc. 2003, 125, 12914–12927; j) X.
Huang, N. Fujioka, G. Pescitelli, F. E. Koehn, R. T. Williamson, K.
Nakanishi, N. Berova, J. Am. Chem. Soc. 2002, 124, 10320–10335;
k) N. Berova, G. Pescitelli, A. G. Petrovica, G. Proni, Chem.
Commun. 2009, 5958–5980; l) L. Xi, H. Fu, W. Yang, J. Yao, Chem.
Commun. 2005, 492–494; m) D. S. Dalisay, S. Tsukamoto, T. F. Mo-
linski, J. Nat. Prod. 2009, 72, 353–359; n) A. Sugasaki, M. Ikeda, M.
Takeuchi, K. Koumoto, S. Shinkai, Tetrahedron 2000, 56, 4717–
4723; o) O. Hirata, Y. Kubo, M. Takeuchi, S. Shinkai, Tetrahedron
2004, 60, 11211–11218.
Synthesis of 8:[12] Triphosgene (0.14 g, 0.40 mmol) in CH2Cl2/Et3N
(3mL:0.2mL) was added to a solution of 4 (0.11 g, 0.40 mmol) in CH2Cl2
(7mL) and the mixture was stirred for 2 h at 08C. Thereafter, a solution
of 7 (0.2 g, 0.27 mmol) in CH2Cl2 (10mL) was added, the reaction mix-
ture was refluxed for 12 h, and then the solvents were evaporated. The
residue was filtered through silica gel with EtOAc. Without further puri-
fication, the product was dissolved in 10% MeOH/CH2Cl2 (20mL) con-
taining ZnACHTUNGTRENNUNG(OAc)2 (0.434 g, 1.98 mmol) and the solution was stirred for
12 h at 258C. The reaction mixture was purified by column chromatogra-
phy on silica, eluting with 20% EtOAc/hexane to give a reddish-purple
solid. The residue was redissolved in THF containing TBAF (78 mL,
0.27 mmol) and the solution was stirred for 30 min at 258C. The reaction
mixture was purified by column chromatography on silica eluting with
EtOAc/hexane (1:4) to give 8 (0.1 g, 37%). 1H NMR (250 MHz, CDCl3,
258C): d=10.26 (s, 2H), 9.42–9.36 (m, 4H), 9.28–9.26 (d, J=4.5 Hz, 2H),
9.06–9.04 (d, J=4.5 Hz, 2H), 8.16–8.13 (d, J=8 Hz, 2H), 7.45–7.40 (m,
4H), 7.33–7.26 (m, 2H), 7.03 (s, 1H), 6.92 (s, 1H), 5.73 (s, 2H), 4.17–4.10
(m, 4H), 3.36 (s, 1H), 1.92–1.81 (m, 4H), 1.48–1.23 (m, 10H), 0.88–
0.82 ppm (m, 6H); MALDI-TOF-MS: m/z: calcd for C61H66N6O3Zn:
996.63 [M+]; found: 994.13.
[5] a) G. Proni, G. Pescitelli, X. Huang, N. Q. Quraishi, K. Nakanishi,
N. Berova, Chem. Commun. 2002, 1590–1591; b) V. V. Borovkov,
J. M. Lintuluoto, G. A. Hembury, M. Sugiura, R. Arakawa, Y. Inoue,
J. Org. Chem. 2003, 68, 7176–7192; c) X. Li, M. Tanasova, C. Vasi-
leiou, B. Borhan, J. Am. Chem. Soc. 2008, 130, 1885–1893; d) Q. F.
Liang, J. J. Liu, J. Chen, Tetrahedron Lett. 2011, 52, 3987–3991.
[6] a) J. F. Lovell, C. S. Jin, E. Huynh, H. Jin, C. Kim, J. L. Rubinstein,
W. C. W. Chan, W. Cao, L. V. Wang, G. Zheng, Nat. Mater. 2011, 10,
324–332; b) C.-H. Lee, S. Lee, H. Yoon, W.-D. Jang, Chem. Eur. J.
2011, 17, 13898–13903; c) W.-D. Jang, C.-H. Lee, M. Osada, M.-S.
Choi, J. Porphyrins Phthalocyanines 2009, 13, 787–793.
Synthesis of 1:[13]
8 (0.1 g, 0.10 mmol) and CuCATHUNTGNRUEGN(OAc)2·H2O (40 mg,
0.20 mmol) were placed in a Schlenk flask. The flask was degassed under
high vacuum and back-filled with N2; this process was repeated three
times. Dry pyridine (10 mL) was added. The reaction mixture was stirred
for 12 h at 258C, and then the solvent was evaporated. The residue was
purified by column chromatography on silica eluting with EtOAc/hexane
(1:3) to give 1 (80 mg, 40%). 1H NMR (400 MHz, CD2Cl2, 258C): d=
10.08 (s, 4H), 9.46 (brs, 4H), 9.30 (brs, 4H), 8.98 (brs, 4H), 8.89 (brs,
4H), 8.04 (brd, J=5.6 Hz, 4H), 7.50 (s, 4H), 7.08 (s, 2H), 6.94 (s, 2H),
6.75 (brs, 6H), 6.70 (brs, 2H), 6.28 (brs, 2H), 4.78 (brs, 2H), 4.19–4.15
(t, J=6.4 Hz, 8H), 1.59–1.05 (m, 20H), 0.84 ppm (s, 12H); 13C NMR
(100 MHz, CD2Cl2, 258C): d=158.59, 150.41, 149.93, 149.89, 149.46,
145.04, 136.11, 133.88, 132.01, 131.94, 130.15, 128.09, 120.73, 120.29,
118.47, 115.02, 106.55, 101.17, 79.58, 79.07, 72.44, 68.85, 61.94, 34.36,
[7] a) T. Yamaguchi, T. Kimura, H. Matsuda, T. Aida, Angew. Chem.
2004, 116, 6510–6515; Angew. Chem. Int. Ed. 2004, 43, 6350–6355;
b) F. Hajjaj, Z. S. Yoon, M.-C. Yoon, J. Park, A. Satake, D. Kim, Y.
Kobuke, J. Am. Chem. Soc. 2006, 128, 4612–4623; c) N. C. Maiti, S.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
7
&
ÞÞ
These are not the final page numbers!

W.-D. Jang et al.
Mazumdar, N. Periasamy, J. Phys. Chem. B 1998, 102, 1528–1538;
d) Y. Egawa, R. Hayashida, J. Anzai, Langmuir 2007, 23, 13146–
13150.
Noll, W. R. Scheidt, D. H. Burns, J. Org. Chem. 2007, 72, 9081–
9087; g) X. P. Bao, H. Zhang, Z. Zhang, L. Wu, Z. Y. Li, Inorg.
Chem. Commun. 2007, 10, 728–730; h) G. Baggi, M. Boiocchi, L.
Fabbrizzi, L. Mosca, Chem. Eur. J. 2011, 17, 9423–9439.
[8] a) F. A. Walker, M. Benson, J. Am. Chem. Soc. 1980, 102, 5530–
5538; b) M. Schmittel, S. K. Samanta, J. Org. Chem. 2010, 75, 5911–
5919; c) C.-H. Lee, H. Yoon, W.-D. Jang, Chem. Eur. J. 2009, 15,
9972–9976; d) C.-H. Lee, H. Yoon, P.-S. Kim, S. Cho, D. Kim, W.-D.
Jang, Chem. Commun. 2011, 47, 4246–4248.
[9] a) B. P. Hay, T. K. Firman, B. A. Moyer, J. Am. Chem. Soc. 2005,
127, 1810–1819; b) M. Pittelkow, C. B. Nielsen, M. A. C. Broeren,
J. L. J. van Dongen, M. H. P. van Genderen, E. W. Meijer, J. B.
Christensen, Chem. Eur. J. 2005, 11, 5126–5135; c) M. A. C. Broe-
ren, B. F. M. de Waal, M. H. P. van Gendern, H. M. H. F. Sanders, G.
Fytas, E. W. Meijer, J. Am. Chem. Soc. 2005, 127, 10334–10343;
d) J.-D. Lee, D. Jang, J.-I. Hong, B. Kor. Chem. Soc. 2010, 31, 2685–
2688; e) J.-D. Lee, Y.-H. Kim, J.-I. Hong, J. Org. Chem. 2010, 75,
7588–7595; f) K. Calderon-Kawasaki, S. Kularatne, Y. H. Li, B. C.
[10] a) L. R. Schmitz, N. L. Allinger, J. Am. Chem. Soc. 1990, 112, 8307–
8315; b) J. B. Sorensen, A. H. Lewin, J. P. Bowen, J. Mol. Struct.
(Theochem) 2003, 623, 145–158.
[11] K.-J. Chang, D. Moon, M. S. Lah, K.-S. Jeong, Angew. Chem. 2005,
117, 8140–8143; Angew. Chem. Int. Ed. 2005, 44, 7926–7929.
ˇ
[12] M. Dudic?, P. Lhotꢃk, I. Stibor, K. Lang, P. Proskova, Org. Lett.
2003, 5, 149–152.
[13] M. Ikeda, A. Sugasaki, Y. Kubo, K. Sugiyasu, M. Takeuchi, S. Shin-
kai, Chem. Lett. 2001, 1266–1267.
Received: February 3, 2012
Revised: June 4, 2012
Published online: && &&, 0000
&
8
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

A Molecular Tweezer for Determining Stereochemistry
FULL PAPER
Molecular tweezer for chirality deter-
mination: A new type of porphyrin-
based molecular tweezer has been
found to exhibit strong CD signals
upon the simultaneous complexation
of chiral carboxylate and achiral di-
Chirality Determination
H. Yoon, C.-H. Lee,
W.-D. Jang* ................... &&&& — &&&&
Absolute Stereochemical Determina-
tion of Chiral Carboxylates Using an
Achiral Molecular Tweezer
ACHTUNGTRENNUNGamine guests (see scheme). By virtue
of this unique feature of the tweezer, it
can be utilized as a highly sensitive
probe for the absolute stereochemical
determination of chiral carboxylates.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
9
&
ÞÞ
These are not the final page numbers!