Chirality-memory molecule: Crystallographic and spectroscopic studies on dynamic molecular recognition events by fully substituted chiral porphyrins

Article abstract of DOI:10.1021/ja000052o

X-ray crystallography of a mandelate complex of a D₂-symmetric saddle-shaped porphyrin such as 2,3,7,8,12,13,17,18-octamethyl-5,15-bis(2′,6′-dimethoxyphenyl)-10, 20-diphenylporphyrin (2) showed that two mandelate anions are hydrogen bonded to t

Full text of DOI:10.1021/ja000052o

5278
J. Am. Chem. Soc. 2000, 122, 5278-5285
Chirality-Memory Molecule: Crystallographic and Spectroscopic
Studies on Dynamic Molecular Recognition Events by Fully
Substituted Chiral Porphyrins
Yukitami Mizuno,‡ Takuzo Aida,*,‡ and Kentaro Yamaguchi†,§
Contribution from the Department of Chemistry and Biotechnology, Graduate School of Engineering,
The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, and Chemical Analysis Center,
Chiba UniVersity, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
ReceiVed January 3, 2000
Abstract: X-ray crystallography of a mandelate complex of a D2-symmetric saddle-shaped porphyrin such as
2,3,7,8,12,13,17,18-octamethyl-5,15-bis(2′,6′-dimethoxyphenyl)-10,20-diphenylporphyrin (2) showed that two
mandelate anions are hydrogen bonded to the pyrrole NH moieties in a monodentate fashion, where the absolute
structure of the porphyrin macrocycle is determined in such a way that the least hindered section of the host
molecule accommodates the phenyl group of the mandelate. IR and 1H NOESY NMR spectroscopies in CH2-
Cl2 indicated that a similar binding mode is operative in solution. A series of fully substituted chiral porphyrins
having different numbers of o-dimethoxyphenyl groups at the meso-positions (1-3) showed different chiral
transfer efficiencies and ring inversion activities. Thermal racemization profiles of protonated 2 in a variety of
achiral carboxylic acids indicated that the ring inversion rate is dependent on the steric factor as well as the
acidity of the carboxylic acid solvent.
Introduction
in Table 1), in which one of the two possible diastereoisomers
is predominantly formed as the result of an induced-fit macro-
cyclic inversion of the saddle conformation (Scheme 1).
Furthermore, even after the chiral guest is replaced by an achiral
carboxylic acid such as acetic acid, 2 can retain its optical
activity over a long period of time at room temperature. Thus,
2 is a conceptually new chirality sensor that can memorize chiral
acid configurations.
In the present paper, we report X-ray crystal structure of the
mandelate complex of 2, spectral profiles of the complex in
solution, and efficiencies of chirality transfer and memory events
with a series of fully substituted chiral porphyrins (1-3), and
we discuss possible factors affecting this particular dynamic
molecular recognition process.
Chiral recognition of asymmetric compounds is one of the
important subjects not only in the field of supramolecular
chemistry but also for medicinal and biomedical applications.
In particular, supramolecular approaches to rapid sensing of the
absolute configurations of asymmetric compounds have become
of increasing interest.1 From this point of view, novel chromo-
phoric host molecules have recently been developed, which can
sense and memorize chiral guest configurations via induced-fit
interactions.1d,i-k We have reported the first example of such
chirality-sensing molecules on the basis of a fully substituted
chiral porphyrin.1d Smith and co-workers have reported that fully
substituted porphyrins such as octaalkyltetraarylporphyrins are
saddle-shaped due to the steric repulsion among the neighboring
substituents on the porphyrin periphery.2 Thus, porphyrin 2
having two different aryl groups at the adjacent meso-positions
is chiral with a symmetry group D2.1d However, the enantiomers
of 2 are hardly separable due to its rapid saddle-to-saddle
macrocyclic inversion (racemization). On the other hand, we
have found that 2 forms a hydrogen-bonded complex with two
molecules of a chiral carboxylic acid such as mandelic acid (4
Results and Discussion
X-ray Crystallography of the Mandelate Complex of 2.
When an ethyl acetate solution of a mixture of porphyrin (2)
and racemic mandelic acid (1:2.1) was once heated at 80 °C
and allowed to stand at room temperature for 2 days, a
crystalline mandelate complex of 2 in the form of a dark
greenish blue prism, appropriate for X-ray crystallography,
formed. Figure 1 shows an ORTEP view of the complex, in
which the porphyrin macrocycle clearly adopts a saddle
conformation with the four pyrrole units pointing up and down
alternately with respect to the least-squares plane of the
‡ The University of Tokyo.
† Responsible for X-ray crystallography.
§ Chiba University.
(1) (a) James, T. D.; Samankumara Sandanayake, K. R. A.; Shinkai, S.
Nature 1995, 374, 345. (b) Kubo, Y.; Maeda, S.; Tokita, S.; Kubo, M.
Nature 1996, 382, 522. (c) Takeuchi, M.; Imada, T.; Shinkai, S. J. Am.
Chem. Soc. 1996, 118, 10658. (d) Furusho, Y.; Kimura, T.; Mizuno, Y.;
Aida, T. J. Am. Chem. Soc. 1997, 119, 5267. (e) Yashima, E.; Matsushima,
T.; Okamoto, Y. J. Am. Chem. Soc. 1997, 119, 6345. (f) Mizutani, T.;
Kurahashi, T.; Murakami, T.; Matsumi, N.; Ogoshi, H. J. Am. Chem. Soc.
1997, 119, 8991. (g) Huang, X.; Rickman, H. B.; Borhan, B.; Berova, N.;
Nakanishi, N. J. Am. Chem. Soc. 1998, 120, 6185. (h) Takeuchi, M.; Imada,
T.; Shinkai, S. Angew. Chem., Int. Ed. Engl. 1998, 37, 2096. (i) Mizuno,
T.; Takeuchi, M.; Hamachi, I.; Nakashima, K.; Shinkai, S. J. Chem. Soc.,
Perkin Trans. 2 1998, 2281. (j) Yashima, E.; Maeda, K.; Okamoto, Y.
Nature 1999, 399, 449. (k) Sugasaki, A.; Ikeda, M.; Takeuchi, M.;
Robertson, A.; Shinkai, S. J. Chem. Soc., Perkin Trans. 1 1999, 3259.
(2) (a) Barkigia, K. M.; Berber, M. D.; Fajer, J.; Medforth, C. J.; Renner,
M. W.; Smith, K. M. J. Am. Chem. Soc. 1990, 112, 8851. (b) Medforth, C.
J.; Berber, M. D.; Smith, K. M.; Shelnutt, J. A. Tetrahedron Lett. 1990,
31, 3719. (c) Senge, M. O.; Forsyth, T. P.; Nguyen, L. T.; Smith, K. M.
Angew. Chem., Int. Ed. Engl. 1994, 33, 2485. (d) Medforth, C. J.; Hobbs,
J. D.; Rodriguez, M. R.; Abraham, R. J.; Smith, K. M.; Shelnutt, J. A.
Inorg. Chem. 1995, 34, 1333. (e) Barkigia, K. M.; Faler, J.; Berber, M. D.;
Smith, K. M. Acta Crystallogr. Sect. C 1995, C51, 511. (f) Nurco, D. J.;
Medforth, C. J.; Forsyth, T. P.; Olmstead, M. M.; Smith, K. M. J. Am.
Chem. Soc. 1996, 118, 10918.
10.1021/ja000052o CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/16/2000

Chirality-Memory Molecule
J. Am. Chem. Soc., Vol. 122, No. 22, 2000 5279
Scheme 1. Schematic Representation of Chirality Transfer
and Memory Events with Saddle-Shaped Chiral Porphyrin
porphyrin. Furthermore, absolute configurations of the mandelate
groups on both sides of the porphyrin are identical with each
other ((S)-configuration in Figure 1). The crystal structure also
shows that the mandelate groups are hydrogen bonded in a
monodentate fashion to the pyrrole units, where one oxygen
atom of the carboxylate moiety is bonded to two opposing NH
functionalities on the same side of the porphyrin, while the other
is hydrogen bonded intramolecularly to the R-hydroxyl group
of the mandelate. The four hydrogen-bonded nitrogen-oxygen
atom distances are almost identical with one another. This
binding mode is in contrast with those reported for the crystal
structures of the acetate complexes of saddle-shaped porphyrins,
in which the acetate groups are hydrogen bonded in a bidentate
fashion to the porphyrin NH.2c,2e Figure 2 shows a graphical
representation of the top view of the complex, in which the
phenyl group of the mandelate is orientated toward the least
Figure 1. ORTEP view of the mandelate complex of 2. The single
crystal was obtained by slow evaporation of an ethyl acetate solution
of a mixture of 2 and racemic mandelic acid (1:2.1). The hydrogen
atoms are omitted for clarity, and the remaining atoms are represented
by Gaussian ellipsoids at the 30% probability level. The asymmetric
carbon atoms of the mandelate moieties here both adopt (S)-configu-
ration. Selected atom distances (Å): N(1)-O(10), 2.806(4); N(3)-
O(10), 2.792(4); N(2)-O(7), 2.849(4); and N(4)-O(7), 2.827(4).
Figure 2. Graphical representation of a top view of the mandelate
complex of 2 (Ph; green, o-(MeO)2Ar; red, (S)-mandelate; yellow). The
image was created based on the atomic coordinates of the crystal
structure in Figure 1.

5280 J. Am. Chem. Soc., Vol. 122, No. 22, 2000
Mizuno et al.
Figure 3. 1H NOESY NMR spectrum (600 ms mixing time) in CD2Cl2 at -90 °C of the (S)-mandelate complex of 2, obtained by recrystallization
in ethyl acetate. For assignment of the signals, see ref 1d.
hindered section of the host molecule bearing a nonsubstituted
meso-phenyl group. On the other hand, the R-hydroxyl group
of the mandelate, hydrogen bonded to the carboxylate C-O
functionality, is pointing toward the tilted-up pyrrole unit, and
the hydrogen atom attached to the asymmetric center of the guest
is oriented toward the most hindered section of the host molecule
having an o-dimethoxyphenyl group. Thus, the chirality transfer
from mandelic acid to 2 is realized by the steric interactions of
the hydrogen-bonded guest molecule with an asymmetric
recognition site (pocket) consisting of two pyrrole units and
two meso-aryl groups. The recognition site with a clockwise
arrangement of tilted-up pyrrole, o-dimethoxyphenyl, tilted-
down pyrrole, and then nonsubstituted phenyl groups (Figure
2) prefers (S)-mandelic acid, while that with the counterclock-
wise arrangement has an opposite preference for the guest
configuration. When the host porphyrin accidentally interacts
with mandelic acid of an unfavorable configuration, it can
simply flip the saddle conformation to invert the steric prefer-
ence (induced-fit interaction).
Spectral Profiles of the Mandelate Complex of 2 in
Solution. Infrared spectroscopy is informative for the mode of
carboxylate anion binding. In general, carboxylate ligands
coordinated to metal ions in a bidentate fashion exhibit
asymmetric and symmetric C-O vibrational frequencies which
are ∼150 cm-1 apart from each other, while the difference in
these two vibrational frequencies for monodentate coordination
is much larger.3 In fact, a KBr pellet sample of the mandelate
complex, obtained from 2 and racemic mandelic acid by
recrystallization in ethyl acetate, displayed asymmetric and
symmetric C-O vibrational frequencies respectively at 1593
and 1354 cm-1,4 whose difference (239 cm-1) is much larger
than the case of bidentate coordination. On the other hand, the
infrared spectrum of the complex in CH2Cl2 was virtually the
same as that of the solid-state sample, giving a frequency
difference of 243 cm-1 between the asymmetric and symmetric
C-O vibrations (1595 and 1352 cm-1, respectively).4 Therefore,
similarly to the case of the crystalline state, the mandelate anions
in solution are most likely hydrogen bonded in a monodentate
fashion to the pyrrole NH moieties of the porphyrin.
As reported previously, the mandelate complex of 2 has been
well characterized by 1H NMR.1d For example, the (S)-
mandelate complex of 2 in CDCl3 at -50 °C showed virtually
a single MeO signal at δ 3.65 ppm due to the o-dimethoxyphenyl
group at the meso-position with a negligibly small MeO signal
at δ 3.85 ppm. The intensity ratio of these two signals was
>99:<1, indicating a diastereoisomeric excess higher than 98%.
1
To obtain geometric information in solution, the H NOESY
NMR spectrum of the complex was taken in CD2Cl2 at -90
°C. As shown in Figure 3, the spectrum displayed NOE cross-
peaks between the phenyl protons (e and f) of the mandelate
and the ortho-protons (a) of the nonsubstituted phenyl groups
at the meso-positions of the porphyrin, whereas no such NOE
cross-peaks were observed between the guest phenyl protons
and the host methoxy protons (g). NOE cross-peaks were also
observed between the meta-/para-protons (e) of the guest phenyl
group and the pyrrole-â-methyl protons (j) close to the non-
substituted phenyl groups of the host molecule. These observa-
tions indicate that the mandelate complex of 2 in solution adopts
a geometrical structure similar to that in the crystalline state.
Structural Effects on Chirality Transfer and Memory
Events. Porphyrins 1 and 3 with a symmetry group C2 are also
chiral when they adopt a saddle conformation. In fact, (R)- and
(S)-mandelate complexes of 1 and 3 in CHCl3 showed charac-
teristic CD bands at the visible absorption bands of the
porphyrins. Furthermore, similarly to 2, these porphyrins
remained optically active even after the mandelate complexes
(diastereoisomeric) were converted into the corresponding
acetate complexes (enantiomeric) when dissolved in acetic acid
(Figure 4).1d Although the CD spectral patterns of optically
(3) (a) Buchler, J. W. In Porphyrin and Metalloporphyrins; Smith, K.
M., Ed.; Elsevier: Amsterdam. 1975; p 222. (b) Deacon, G. B.; Philips, R.
J. Coord. Chem. ReV. 1980, 33, 227.
(4) See Supporting Information.

Chirality-Memory Molecule
J. Am. Chem. Soc., Vol. 122, No. 22, 2000 5281
Figure 4. Circular dichroism (CD) spectra in acetic acid at 23 °C of
the protonated forms of 1 (A(R), A(S)), 2 (B(R), B(S)), and 3 (C(R), C(S)),
derived from the (R)- and (S)-mandelate complexes obtained by
recrystallization in ethyl acetate.
Figure 5. Thermal racemization profiles in acetic acid at 74 °C of the
protonated forms of 1-3, derived from the (S)-mandelate complexes
obtained by recrystallization in ethyl acetate. Changes in ∆ꢀ at 478
nm for 1 (A) and 482 nm for 2 (B) and 3 (C).
active 1 (Figure 4A) and 3 (Figure 4C) were similar to that of
2 (Figure 4B), the intensities of the CD bands were smaller.
Accordingly, 1H NMR spectra of the (S)-mandelate complexes
of 1 and 3 clearly showed some characteristic signals due to
diastereoisomers. In CDCl3 at -50 °C, the (S)-mandelate
complex of 1 showed two MeO signals at δ 3.78 and 3.88 ppm
due to the o-dimethoxyphenyl group at the meso-position with
an intensity ratio of 22:77,4 from which the diastereoisomeric
excess was evaluated to be 55%. Similarly, the (S)-mandelate
complex of 3, under the same conditions, showed two signals
at δ 8.62 and 8.19 ppm assignable to the ortho-protons of
the nonsubstituted meso-phenyl group with an intensity ratio
of 87:13,4 which corresponds to the diastereoisomeric excess
of 74%. From the crystal structure of the mandelate complex
of 2 (Figure 2), the lower efficiencies of the chirality transfer,
as observed for 1 and 3 having three identical meso-aryl groups,
are considered reasonable, since the chiral recognition of
mandelate anion requires two adjacent meso-aryl groups of
different steric bulk.
Of further interest is the fact that the lifetimes of the chirality
memory of 1-3 in acetic acid were considerably different from
one another. For example, when the crystals of the (S)-mandelate
complex of 2 were dissolved in acetic acid at 74 °C, the optical
activity of 2 in the protonated form was decreased with a half-
life of 5 min (Figure 5B). On the other hand, the optical activity
of protonated 1, under the same conditions, lasted for a longer
period of time (half-life, 39 min; Figure 5A) than that of
protonated 2. In contrast, protonated 3 showed the shortest half-
life of the optical activity (1.5 min; Figure 5C) among the three
porphyrins examined. The observed thermal racemization is due
to the macrocyclic inversion of the saddle conformation. From
the thermal racemization profiles, the activation free energies
at 298 K (∆G‡298) for the macrocyclic inversion of protonated
1-3 in acetic acid were evaluated to be 28.0, 26.1, and 24.4
kcal mol-1, respectively.5 Thus, the ortho-substituents on the
meso-aryl groups of the porphyrin appear to affect the macro-
cyclic inversion process of the saddle conformation.
Figure 6. Half-lives of the optical activity of the protonated form
of 2 (derived from the (S)-mandelate complex obtained by recrystal-
lization in ethyl acetate) in carboxylic acids H(CH2)nCO2H, (n ) 1-5)
and (CH3)2CHCO2H at 57 °C. pKa values of the acids are 4.76 (n )
1), 4.87 (n ) 2), 4.82 (n ) 3), 4.84 (n ) 4), 4.88 (n ) 5), and 4.79
((CH3)2CHCO2H) at 25 °C.8
acid (HCtCCO2H; 1.84), the half-lives at 57 °C of the optical
activity of protonated 2 were 770 and 820 min, respectively,
which are more than 1 order of magnitude longer than that in
acetic acid (53 min, pKa at 25 °C ) 4.76) under the same
conditions. Along this line, the racemization profile of proto-
nated 2 was also investigated in carboxylic acids with different
hydrocarbon chains (H(CH2)nCO2H, n ) 1-5) at 57 °C.
Interestingly, the half-life of the optical activity clearly showed
a bell-shaped dependency on the hydrocarbon chain length of
H(CH2)nCO2H, although the pKa values of these acids are all
in the range 4.7-4.9 (Figure 6). In particular, the slowest
racemization was observed in n-butyric acid (n ) 3, pKa ) 4.82),
where the half-life of the optical activity (540 min) was almost
1 order of magnitude longer than that in acetic acid. On the
other hand, when isobutyric acid (pKa ) 4.79) was used as a
solvent in place of n-butyric acid, the half-life of the optical
In relation to this trend, the inversion rate of the saddle
conformation was found to depend also on the acidity and steric
bulk of the carboxylic acid solvent. In highly acidic solvents
such as dichloroacetic acid (pKa at 25 °C ) 1.30) and propiolic
(5) For activation free energies of the macrocyclic inversion of octa-
ethyltetraphenylporphyrin free base and metal complexes in pyridine, see
ref 2a.

5282 J. Am. Chem. Soc., Vol. 122, No. 22, 2000
Mizuno et al.
Scheme 2. A Possible Equilibrium for Saddle-Shaped
Porphyrins in Carboxylic Acid
activity was short (11 min). In carboxylic acids, there should
be at least three different porphyrin species, i.e., protonated and
complexed porphyrin (a), protonated but uncomplexed porphyrin
(b), and nonprotonated and uncomplexed porphyrin (c) (Scheme
2), where neutral species (c) most likely undergoes thermal-
induced racemization (macrocyclic inversion) via a planar
transition state. In contrast, species (b) in a diprotonated form
is highly reluctant to racemization, since the planar transition
state is energetically unfavorable due to an electrostatic repulsion
among the positively charged nitrogen atoms. The racemization
of hydrogen-bonded complex (a) is also unlikely, because of a
possible locking of the saddle-shaped conformation. In car-
boxylic acids of low pKa values (<2) such as dichloroacetic
acid and propiolic acid, diprotonated species (b) must be
predominant. On the other hand, in carboxylic acids with pKa
of 4.7-4.9, the porphyrin should exist mostly in hydrogen-
bonded form (a), where a van der Waals interaction between
the saddle-shaped pocket of the porphyrin and the hydrocarbon
chain of the acid would stabilize the hydrogen-bonding interac-
tion (n-butyric acid). However, in sterically hindered carboxylic
acids such as isobutyric acid, hydrogen-bonded species (a) must
be energetically unstable and frequently dissociate into neutral
species (c), which is active for the macrocyclic inversion.
Performance of 2 as a Chirality Sensor. Among saddle-
shaped porphyrins 1-3, 2 with the highest chirality-transfer
efficiency was chosen, and its performance as chirality sensor
was investigated in detail. Upon titration of 2 with (S)-mandelic
acid in 1,2-dichloroethane (DCE, [2] ) ∼10-4 M) at 24 °C,
the intensities of the CD bands of protonated 2, measured in
acetic acid ([2] ) ∼10-6 M), were increased as the mole ratio
[mandelic acid]/[2] was higher and finally reached a plateau
when the guest/host mole ratio exceeded 2.4 This result indicates
that the two-to-one complexation of mandelic acid with 2 is
established even under such dilute conditions. On the other hand,
when 2 was mixed with mandelic acid of different optical
purities in DCE ([2] ) ∼10-4 M, [mandelic acid]/[2] ) 2.1),
the observed CD intensities in acetic acid for the protonated
form of 2 displayed a linear correlation with the enantiomeric
excess (ee) of the guest (Figure 7). Thus, the optical purity of
mandelic acid can be determined from the intensities of the CD
bands of 2.
Figure 7. Circular dichroism (CD) spectral responses of 2 toward
mandelic acid of different optical purities. 2 and the acid were mixed
at a mole ratio of 1:2.1 in 1,2-dichloroethane, and the solution was
poured into acetic acid for CD spectroscopy at 24 °C. ∆ꢀ481 and ∆ꢀ464
represent the intensities of the CD bands at 481 and 464 nm,
respectively, and |∆ꢀ481 - ∆ꢀ464 100%ee
|
represents their absolute differ-
ence for enantiomerically pure mandelic acid.
13, and 15 may be located on a borderline for the prediction,
since the steric bulks of the corresponding substituents at the
chiral center are not much different from each other. 2 can also
be applicable to the chirality sensing of acids 16 and 17 having
a quaternary asymmetric center. Of further interest, 2 was unable
to read out the chirality of acid 18 with a primary carboxylic
acid functionality, but the complex of 2 with 19 was CD active
although the chiral center of the acid is separated by five bonds
from the carboxylic acid residue. 2 can also diagnose the
absolute configurations of a sugar derivative such as 20, R- and
â-amino acid derivatives 21-26, and phosphoric acids 27 and
28. It should be emphasized here that saddle-shaped porphyrin
2 as a chirality sensor can take great advantage of not only its
enhanced circular dichroism activity in the visible region6 but
also its ability of memorizing the chiral recognition event. This
allows us to determine the guest configuration on the basis of
the inherent CD profile of 2 without any interfering effects of
the guest molecules.
Conclusion
In the present paper, we succeeded in the first crystallographic
determination of the absolute structure of a chiral saddle-shaped
porphyrin (2). This achievement allows us to make a direct
structural correlation of the absolute conformation of the saddle
in solution with its circular dichroism profile. Furthermore, the
crystal structure of the complex with mandelic acid, together
with the notable structural effects on the chirality transfer and
memory events, will also provide a new strategy for the
molecular design of chirality sensors that can be applied to a
wider variety of chiral substrates. Transfer of structural informa-
tion in noncovalent systems is one of the challenging subjects
in supramolecular chemistry involving dynamic molecular
recognition events. Chemical amplification of the transferred
In addition to mandelic acid, a wide variety of chiral
carboxylic acids (Table 1) can be diagnosed by 2,1d where the
absolute configurations of 5-8 and 10-14 were all predictable,
by analogy to the case of mandelic acid (4), from the sign of
the CD band of 2 at 482 nm in acetic acid after complexation
with the carboxylic acids: The CD sign apparently showed a
certain correlation with the relative steric bulk of the two
substituents at the asymmetric center other than the hydrogen
atom and carboxylic acid functionality. In this sense, acids 9,
(6) (a) Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopys
Exciton Coupling in Organic Stereochemistry; University Science Books:
Mill Valley, CA, 1983. (b) Nakanishi, K.; Berova, N. In Circular
DichroismsPrinciples and Applications; Nakanishi, K., Berova, N., Woody,
R. W., Eds.; VCH: New York, 1994; pp 361-398.

Chirality-Memory Molecule
J. Am. Chem. Soc., Vol. 122, No. 22, 2000 5283
Table 1. CD Sign at 482 nm of 2 in Acetic Acid after Complexation in Ethyl Acetate/1,2-Dichloroethane
were distilled from molecular sieves 4A (Aldrich) and stored under
information will be a highly interesting subject worthy of further
investigation.
nitrogen. p-Chloranil (Aldrich) was used as received.
5-Phenyl-2,3,7,8-tetramethylpyrromethane:7 To a CH2Cl2 (5.0 mL)
solution of a mixture of ethyl 3,4-dimethyl-2-pyrrolecarboxylate7a (508
mg, 3.04 mmol) and benzaldehyde (0.15 mL, 1.4 mmol) was added
Experimental Section
Materials. Dichloromethane (CH2Cl2), 1,2-dichloroethane (DCE),
and ethyl acetate (EtOAc) were distilled from CaH2 under nitrogen.
Ethylene glycol was distilled from CaSO4 under reduced pressure. These
solvents were stored under nitrogen. BF3 etherate and benzaldehyde
were distilled under reduced pressure and stored in a nitrogen
atmosphere. Carboxylic acids used as solvents for CD measurements
(7) (a) Ono, N.; Kawamura, H.; Bougauchi, M.; Maruyama, K. Tetra-
hedron 1990, 46, 7483. (b) Wallace, D. M.; Leung, S. H.; Senge, M. O.;
Smith, K. M. J. Org. Chem. 1993, 58, 7245. (c) Lindsey, J. S.; MacCrum,
K. A.; Tyhonas, J. S.; Chaung, Y. J. Org. Chem. 1994, 59, 579.
(8) Dean, J. A. Lange’s Handbook of Chemistry, 13th ed.; McGraw-
Hill: New York, 1985; Section 5.

5284 J. Am. Chem. Soc., Vol. 122, No. 22, 2000
Mizuno et al.
1
BF3 etherate (0.02 mL, 0.2 mmol), and the mixture was stirred under
nitrogen for 24 h at room temperature. Then, the mixture was shaken
with aqueous NaHCO3 and extracted with CH2Cl2. The combined
extracts were washed with brine, and the organic phase that separated
was dried over Na2SO4 and evaporated to dryness, to give diethyl
5-phenyl-2,3,7,8-tetramethylpyrromethane-1,9-dicarboxylate in 84%
dm3 cm-1): 397 (26900), 466 (270500), 627 (8800), 683 (28900). H
NMR (270 MHz, CDCl3, 25 °C): δ 8.30-8.21 (6H, m, o-H in C6H5),
7.75-7.65 (10H, m, m-/p-H in C6H5 + p-H in C6H3(OMe)2), 6.93
(2H, d, J ) 8.34 Hz, m-H in C6H3(OMe)2), 3.76 (6H, s, OCH3 in
C6H3(OMe)2), 2.07 (6H, s, pyrrole-â-CH3 closest to C6H3(OMe)2), 1.88
(6H, s, pyrrole-â-CH3 second closest to C6H3(OMe)2), 1.83 (12H, s,
pyrrole-â-CH3 between two Ph groups), -2.43 and -2.54 (2H, s, NH;
observable at -90 °C). HRMS calcd for C54H51N4O2 (M + H+)
787.4012, obsd 787.3987.
1
yield (538 mg). H NMR (270 MHz, CDCl3, 25 °C): δ 8.21 (2H, s,
NH), 7.34 (3H, m, m-/p-H in C6H5), 7.11 (2H, d, J ) 3.5 Hz, o-H in
C6H5), 5.51 (1H, s, CH), 4.28 (4H, q, J ) 7.1 Hz, CO2CH2Me), 2.24
and 1.83 (12H, s, pyrrole-â-CH3), 1.35 (6H, t, J ) 7.1 Hz, CO2-
CH2CH3). FAB-MS calcd for C21H26N2O2 (M +) 422, obsd 422. The
dicarboxylate (157 mg, 0.373 mmol) was dissolved in ethylene glycol
(6.5 mL) containing NaOH (98 mg, 2.4 mmol), and the solution was
refluxed for 0.5 h. Then, the reaction mixture was shaken with CH2-
Cl2/water and extracted with CH2Cl2. The combined extracts were
washed with brine, and the organic phase that separated was dried over
Na2SO4 and evaporated to dryness. The residue was dissolved in
benzene and freeze-dried to give 5-phenyl-2,3,7,8-tetramethylpyrro-
methane, quantitatively, as a brown powder. 1H NMR (270 MHz,
CDCl3, 25 °C): δ 7.30 (3H, m, m-/p-H in C6H5), 7.14 (2H, d, J ) 7.8
Hz, o-H in C6H5), 6.40 (2H, d, J ) 1.5 Hz, pyrrole-R-H), 5.49 (1H, s,
CH), 2.03 and 1.81 (12H, s, pyrrole-â-CH3). FAB-MS calcd for
C21H26N2O2 (M +) 278, obsd 278.
2,3,7,8,12,13,17,18-Octamethyl-5,15-bis(2′,6′-dimethoxyphenyl)-
10,20-diphenylporphyrin (2)1d and 2,3,7,8,12,13,17,18-octamethyl-
5,10,15-tris(2′,6′-dimethoxyphenyl)-20-phenylporphyrin (3): To a
CH2Cl2 (8.0 mL) solution of a mixture of benzaldehyde (0.08 mL, 0.8
mmol), 5-(2′,6′-dimethoxyphenyl)-2,3,7,8-tetramethylpyrromethane (219
mg, 0.648 mmol), and a dehydrating agent such as molecular sieves
4A (1 g) was added BF3 etherate (0.01 mL, 0.08 mmol), and the mixture
was stirred under nitrogen at room temperature. After 2 h, p-chloranil
(244 mg, 0.994 mmol) was added to the reaction mixture, and stirring
was continued for 2 h. Then, molecular sieves 4A were removed by
filtration, and a black filtrate was shaken with aqueous Na2S2O3 and
extracted with CH2Cl2. The combined extracts were washed with brine,
and the organic phase that separated was dried over Na2SO4 and
evaporated to dryness. Then, the residue was chromatographed on
alumina with CHCl3 containing 0.5% Et2NH as eluent, where the first
and second green bands were collected and subjected to recrystallization
from CH2Cl2/ethanolic KOH, to give 2 and 3 in 13% (35.8 mg) and
4% (8.1 mg) yield, respectively. 2: UV/vis (AcOH), λmax, nm (ꢀ, mol-1
5-(2′,6′-Dimethoxyphenyl)-2,3,7,8-tetramethylpyrromethane:7
To a CH2Cl2 (15 mL) solution of a mixture of ethyl 3,4-dimethyl-2-
pyrrolecarboxylate7a (2.63 g, 15.7 mmol) and 2,6-dimethoxybenz-
aldehyde (1.43 g, 8.62 mmol) was added BF3 etherate (0.11 mL, 0.87
mmol), and the mixture was stirred under nitrogen for 24 h at room
temperature. Then, the reaction mixture was shaken with aqueous
NaHCO3 and extracted with CH2Cl2. The combined extracts were
washed with brine, and the organic phase that separated was dried
over Na2SO4 and evaporated to dryness. Then, the residue was subjected
to recrystallization from EtOH, to give diethyl 5-(2′,6′-dimethoxy-
phenyl)-2,3,7,8-tetramethylpyrromethane-1,9-dicarboxylate in 88%
dm3 cm-1): 467 (220000), 619 (8300), 680 (21000). H NMR (270
1
MHz, CDCl3, 23 °C): δ 8.21-8.14 (4H, m, o-H in C6H5), 7.70-7.65
(6H, m, m-/p-H in C6H5), 7.64 (2H, t, J ) 8.4 Hz, p-H in C6H3(OMe)2),
6.93 (4H, d, J ) 8.4 Hz, m-H in C6H3(OMe)2), 3.69 (12H, s, OCH3 in
C6H3(OMe)2), 2.05 (12H, s, pyrrole-â-CH3 close to C6H3(OMe)2), 1.84
(12H, s, pyrrole-â-CH3 close to C6H5), -1.9 (2H, s, NH). HRMS calcd
for C58H59N4O6 (M + H+) 847.4223, obsd 847.4279. 3: UV/vis
(AcOH), λmax, nm (ꢀ, mol-1 dm3 cm-1): 385 (24600), 467 (241200),
617 (8800), 674 (20100). 1H NMR (270 MHz, CDCl3, 23 °C): δ
8.20-8.16 (2H, m, o-H in C6H5), 7.71-7.59 (12H, m, m-/p-H in
C6H5 + p-H in C6H3(OMe)2), 6.93 (4H, d, J ) 8.3 Hz, m-H in 5-/15-
C6H3(OMe)2), 6.92 (2H, d, J ) 8.3 Hz, m-H in 10-C6H3(OMe)2),
3.67 (12H, s, OCH3 in 5-/15-C6H3(OMe)2), 3.63 (6H, s, OCH3 in 10-
C6H3(OMe)2), 2.06 (18H, s, pyrrole-â-CH3 close to C6H3(OMe)2), 1.85
(6H, s, pyrrole-â-CH3 close to C6H5), -2.59 and -2.63 (2H, s, NH;
observable at -90 °C). HRMS calcd for C58H59N4O6 (M + H+)
907.4435, obsd 907.4485.
1
yield (3.32 g). H NMR (270 MHz, CDCl3, 25 °C): δ 9.11 (2H, s,
NH), 7.21 (1H, t, J ) 8,3 Hz, p-H in C6H3(OMe)2), 6.63 (2H, d, J )
8.3 Hz, m-H in C6H3(OMe)2), 6.23 (1H, s, CH), 4.29 (4H, q, J ) 7.1
Hz, CO2CH2Me), 3.83 (6H, s, OCH3), 2.24 and 1.83 (12H, s, pyrrole-
â-CH3), 1.35 (6H, t, J ) 7.1 Hz, CO2CH2CH3). FAB-MS calcd
for C27H34N2O6 (M +) 482, obsd 482. Anal. Calcd. for C27H34N2O6:
C, 67.20; H, 7.10; N, 5.80. Found: C, 67.30; H, 7.02; N, 5.97. The
dicarboxylate (425 mg) was dissolved in ethylene glycol (8.0 mL)
containing NaOH (189 mg, 4.73 mmol), and the solution was refluxed
for 0.5 h. Then, the reaction mixture was shaken with CH2Cl2/water,
and extracted with CH2Cl2. The combined extracts were washed with
brine, and the organic phase that separated was dried over Na2SO4 and
evaporated to dryness. Then, the residue was dissolved in benzene and
freeze-dried to give 5-(2′,6′-dimethoxyphenyl)-2,3,7,8-tetramethylpyr-
Measurements. NMR spectra were measured on a JEOL type GSX-
270 spectrometer operating at 270 MHz. UV-visible spectra were
recorded on a JASCO type V-560 spectrophotometer. CD spectra were
recorded on a JASCO type J-720 spectropolarimeter. IR spectra were
recorded in a KBr pellet or CH2Cl2 at 21-23 °C on a JASCO type
FT-IR-5300 infrared spectrometer.
1
romethane, quantitatively, as a brown powder. H NMR (270 MHz,
CDCl3, 25 °C): δ 8.26 (2H, s, br, NH), 7.14 (1H, t, J ) 8.3 Hz, p-H
in C6H5), 6.61 (2H, d, J ) 8.3 Hz, m-H in C6H5), 6.38 (2H, d, J ) 1.2
Hz, pyrrole-R-H), 6.19 (1H, s, CH), 3.7 (6H, s, OCH3), 2.00 and 1.82
(12H, s, pyrrole-â-CH3). HRMS calcd for C21H26N2O2 (M + H+)
338.1994, obsd 338.2010.
Crystallographic Analysis. An ethyl acetate (EtOAc) solution of a
mixture of 2 (6 mg, 7 mmol) and racemic mandelic acid (2 mg, 14
mmol) was once heated at 80 °C and then allowed to cool to room
temperature. The solution was allowed to stand at room temperature
in a glass bottle with a porous cap to allow slow evaporation of the
solvent, to give in 2 days a crystalline mandelate complex of 2. X-ray
crystallographic analysis was undertaken using a charge coupled device
(CCD) diffractometer Bruker SMART 1000 with monochromated Mo
KR radiation (λ ) 0.7101 Å) using SAINT (Siemens) for cell refinement
and data reduction. Absorption correction was not applied. The crystal
structure was solved by using SIR97 and refined on F by the full-
matrix least-squares method included in TEXSAN ver. 1.1 (Molecular
Structure Co.). Non-H atoms were refined anisotropically. All H atoms
with isotropic thermal parameters were located on the calculated
positions (not refined). Crystal and experimental data: dark greenish
blue prism (0.45 × 0.40 × 0.35 mm), C56H56N4O4‚2C6H7O3‚2C4H8O2‚
3H2O (two ethyl acetate and three water molecules were included in
an asymmetric unit), triclinic P1h, a ) 13.888(2) Å, b ) 15.866(2) Å,
c ) 17.869(2) Å, R ) 77.632(2)°, â ) 73.910(2)°, γ ) 77.116(2)°,
V ) 3638.7(6) Å3, Z ) 2, Dcalcd ) 1.261 g‚cm-3, F000 ) 1472, µ(Mo
KR) ) 0.88 cm-1; T ) -100 °C, 2θmax ) 57.0°, ω scans, 21970
2,3,7,8,12,13,17,18-Octamethyl-5-(2′,6′-dimethoxyphenyl)-10,15,20-
triphenylporphyrin (1): To a CH2Cl2 (27 mL) solution of a mixture
of benzaldehyde (0.27 mL, 2.7 mmol), 5-(2′,6′-dimethoxyphenyl)-
2,3,7,8-tetramethylpyrromethane (379 mg, 1.12 mmol), 5-phenyl-
2,3,7,8-tetramethylpyrromethane (276 mg, 0.990 mmol), and a dehy-
drating agent such as molecular sieves 4A (2 g) was added BF3 etherate
(0.035 mL, 0.279 mmol), and the mixture was stirred under nitrogen
at room temperature. After 2 h, p-chloranil (778 mg, 3.16 mmol) was
added to the reaction mixture, and stirring was continued for 2 h. Then,
molecular sieves 4A were removed by filtration, and a black filtrate
was shaken with aqueous Na2S2O3 and extracted with CH2Cl2. The
combined extracts were washed with brine, and the organic phase that
separated was dried over Na2SO4 and evaporated to dryness. Then, the
residue was chromatographed on alumina with CHCl3/hexane (7:3)
containing 3% Et2NH as eluent, where the second green band was
collected and subjected to recrystallization from CH2Cl2/ethanolic KOH,
to give 1 in 7% yield (27.9 mg). UV/vis (AcOH): λmax, nm (ꢀ, mol-1

Chirality-Memory Molecule
J. Am. Chem. Soc., Vol. 122, No. 22, 2000 5285
reflections measured, 16015 unique, 6975 with I > 3.0σ(I), 911
(No. 7) for final positional parameters for the crystalline (()-
mandelate complex of 2 (an X-ray crystallographic file, in CIF
format), IR spectra (1800-1200 cm-1) of a KBr pellet sample
and a CH2Cl2 solution of the (()-mandelate complex of 2 (No.
variables, R ) 0.066, Rw ) 0.086, S ) 1.97, (∆/σ)max ) 0.25, Fmax
)
0.47 e-/Å, Fmin ) -0.41 e-/Å. The ORTEP view was drawn by CAChe
(Oxford Molecular Ltd.).
1
8), H NMR spectra (CDCl3, -50 °C) of the (S)-mandelate
Acknowledgment. Y.M. thanks the JSPS Research Fellow-
complexes of 1 and 3 (Nos. 9, 10), and results of CD titration
of 2 with (S)-mandelic acid (No. 11) (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
ship for Young Scientists.
Supporting Information Available: Numbering scheme
(Nos. 1, 2), tables of atomic coordinates and isotropic displace-
ment parameters (No. 3), anisotropic displacement parameters
(No. 4), bond lengths (No. 5), angles (No. 6), torsion angles
JA000052O