Helical chirality induction of expanded porphyrin analogues

Article abstract of DOI:10.1007/s12039-012-0315-4

Expanded porphyrin analogues with unique figure-eight conformation were prepared by way of useful pyrrole intermediates such as bis(azafulvene)s and 2-borylpyrrole. Supramolecular chirogenesis of cyclooctapyrrole O1 with 32π-cycloconjugation was successfu

Full text of DOI:10.1007/s12039-012-0315-4

c
J. Chem. Sci. Vol. 124, No. 6, November 2012, pp. 1151–1163. ꢀ Indian Academy of Sciences.
Helical chirality induction of expanded porphyrin analogues
JUN-ICHIRO SETSUNE
Department of Chemistry, Graduate School of Science, Kobe University, Nada-ku, Kobe 657 8501, Japan
e-mail: setsunej@kobe-u.ac.jp
Abstract. Expanded porphyrin analogues with unique figure-eight conformation were prepared by way of
useful pyrrole intermediates such as bis(azafulvene)s and 2-borylpyrrole. Supramolecular chirogenesis of
cyclooctapyrrole O1 with 32π-cycloconjugation was successfully applied to determine absolute configuration
of chiral carboxylic acids. Dinuclear CuII complex of cyclooctapyrrole O2 with interrupted π-conjugation was
resolved by HPLC into enantiomers and their helical handedness was determined by theoretical simulation of
their CD spectral pattern. Enantioselective induction of helicity in the metal helicate formation in the presence
of a chiral promoter was demonstrated by using (R)-(+)-1-(1-phenyl)ethylamine that favoured P, P helicity.
Dinuclear CoII complexes of cyclotetrapyrroletetrapyridine O3 were found to be substitution labile and pick
up amino acid anions in water. Those amino acid complexes of O3Co2 were rendered to adopt a particular
unidirectional helical conformation preferentially depending on the ligated amino acid anion.
Keywords. Porphyrin analogues; metal complexes; helical chirality; chirality sensing.
1. Introduction
cyclooctapyrroles with a figure-eight conformation to
chirality sensing and asymmetric catalysis is of great
interest. To this end, we have been interested in deve-
loping properly designed expanded porphyrin ana-
logues O1, O2, and O3 to be applied for inducing
helical chirality (chart 1).
Chemistry of expanded porphyrins has made great
progress in the last couple of decades.1 Novel struc-
tures, properties, and reactions have been reported. The
figure-eight conformation as evidenced by X-ray crystal
structures of [40]decaphyrin(1.0.1.0.0.1.0.1.0.0), [32]
octaphyrin(1.0.1.0.1.0.1.0), [34]octaphyrin(1.1.1.0.1.1.1.0),
and [36]octaphyrin(2.1.0.1.2.1.0.1) in the mid 90’s is
one of the most intriguing aspects of expanded por-
phyrins.2,3 Topological feature of the double half twist
of this figure-eight conformation in relation to the num-
ber of π-electrons attracts much attention in the context
of aromaticity and antiaromaticity.4 On the other hand,
helical chirality originated from figure-eight conforma-
tion of cyclooctapyrroles was demonstrated by Vogel.5
That is, HPLC separation of [36]octaphyrin(2.1.0.1.
2.1.0.1) on a chiral phase was successful to determine
helical handedness of the Pd complex by X-ray crystal-
lography. The relationship between the helical handed-
ness of the free base [36]octaphyrin(2.1.0.1.2.1.0.1) and
the chiroptical feature has recently been unambiguously
determined by the theoretical study.6 Since the elec-
tronic circular dichroism arising from the chromophore
of porphyrins and the related compounds is a powerful
tool for studying chiral materials, porphyrins have been
frequently utilized in chiral sensing and memory.7,8 For
example, complexation with chiral ligands induced the
bisporphyrin tweezer to take a particular conformation
with an excess of unidirectional screw between the two
porphyrin moieties.7a–d In this context, application of
2. Synthesis
2.1 Synthesis by way of bis(azafulvene)
Connecting two pyrrole units is a fundamental reac-
tion in the porphyrinoid synthesis and there are two
major such reactions to form dipyrrylmethene units
1; that as in the Rothemund type reaction from
pyrrole and aldehyde (route A-D) and that as in
the MacDonald-[2+2] type reaction from dipyrryl-
methane and dipyrrylmethane-5,5ꢁ-dialdehyde (route
B) in scheme 1.9,10 The latter generates stable dipyrryl-
methane 1 directly by acid catalysed dehydration
but strongly acidic reaction conditions are usually
employed, while the former uses drastic reaction con-
ditions to make in situ oxidation of the initially formed
dipyrrylmethane 2. Since dipyrrylmethane and water
under acidic conditions proceed to fragmentation as a
backward reaction, relatively low efficiency and scram-
bling of the pyrrole units in the product macrocycles
become problematic. Lindsey improved these situations
by using two-step, one-flask, room-temperature proce-
dure (route A-D).11 That is, dipyrrylmethane formation
1151

1152
Jun-Ichiro Setsune
Chart 1. Expanded porphyrin analogues with figure-eight conformation.
using low reactant concentration in CH2Cl2 followed
Two examples of synthesis of porphyrin analogues
by addition of oxidizing agent such as 2,3-dichloro-5,6- are shown in schemes 3 and 4 where bis(azafulvene)
dicyano-1,4-benzoquinone (DDQ). Pyrrole-2-carbinol 5 and bis(azafulvenyl)dimethylmethane 6 were suc-
3 can be a good starting material that is really an inter- cessfully used under neutral conditions. Vilsmeier–
mediate in the reaction of pyrrole and aldehyde of route Haack aroylation followed by NaBH4 reduction accord-
A. Although Lindsey procedure starting from 3 was ing to the Lindsey protocol gave 2,2ꢁ-bipyrrole-5,
successfully applied for regioselective [2+2]-type por- 5ꢁ-di(arylcarbinol) in good yield and then it was cleanly
phyrin synthesis (route C-D), the generated water still converted to bis(azafulvene) 5 as shown in scheme 3.
causes undesired results in some cases.
When 5 was reacted with the parent 2,2-bipyrrole at
We have found that 3 itself is cleanly dehydrated by room temperature and then with DDQ, a mixture of
the reaction with (Boc)2O in the presence of DMAP porphyrinoid homologues with 8, 12, 16, 20, and 24
to give isolable azafulvene 4 in good yield.12 It turned pyrrole units was isolated in 22, 3, 4, 3, and 2%
out that 4 was reactive enough to act as Michael type yield, respectively.13 Since this reaction does not gene-
acceptor when reacted with α-free pyrrole at room rate homologues having 6, 10, 14, 18, and 22 pyrrole
temperature in the absence of acid catalyst (route E-D). units, separation of the products mixture is much easier
The reaction of 4 with pyrrole is not dehydration but than those derived from TFA-catalysed condensation of
addition and can be performed under neutral conditions. 2,2ꢁ-bipyrrole and benzaldehyde where cyclohexapyr-
Therefore, acid-catalysed fragmentation-cyclization role and cyclooctapyrrole O1 are the only isolable
sequence responsible for the redistribution equilibrium products.14
among cyclooligomers of different ring size to favour
An alternative method to get such dipyrrole-
thermodynamically more stable small ones as shown in 5,5ꢁdicarbinols is Vilsmeier–Haack formylation fol-
scheme 2 is not occurring in the synthesis of porphyri- lowed by addition of aryllithium as shown in scheme 4.
noids. This azafulvene methodology is suitable for the The resulting gem-dimethyl-2,2ꢁ-dipyrrylmethane-5,5ꢁ-
preparation of large sized porphyrinoids.
di(arylcarbinol) was converted to bis(azafulvene) 6.
Scheme 1. Azafulvene 4 as a useful precursor for connecting pyrrole units in the synthesis of porphyrinoids.

Helical porphyrin analogues
1153
Scheme 2. Acid-catalysed fragmentation–cyclization sequence in the porphyrin synthesis.
Scheme 3. Synthesis of expanded porphyrins using bis(azafulvene) 5.
Scheme 4. Synthesis of expanded porphyrins using bis(azafulvene) 6.

1154
Jun-Ichiro Setsune
Then, 6 was allowed to react with 2,2ꢁ-bipyrrole that is readily obtainable by Barton–Zard pyrrole
to generate a mixture of porphyrinoid homologues synthesis.16 2-Borylpyrrole was used successfully for
with different ring sizes from cyclotetrapyrrole to coupling with various commercially available aro-
cyclooctacosapyrrole after DDQ oxidation.15 Up to matic dihalides in the Suzuki–Miyaura cross coupling
cyclotetratetracontapyrrole having 44 pyrrole units was reactions as shown in scheme 5.17 6,6ꢁ-Di-(2-pyrryl)-
separated by GPC and characterized by mass analy- 2,2ꢁ-Bipyridine was readily obtained from 6,6ꢁ-
sis in this reaction and macrocycles having scrambled dibromo-2,2ꢁ-bipyridine and then used for synthesizing
arrangements of two components was not detected. This cyclotetrapyrroletetrapyridine O3.18
cyclooctapyrrole O2 has two parts of π-conjugated
tetrapyrrole chromophores are connected by sp3
carbons.
3. Helical chirality induction
3.1 Chirality sensing of carboxylic acids by O1
2.2 Synthesis by way of 2-borylpyrrole
Development of new building blocks is of great Facile methods for the determination of molecular chi-
importance to make porphyrin analogues with unique rality are of increasing interest in view of the role of
structure and property. Dipyrrylarenes are potential can- chirality in natural phenomena and medicine. Based on
didate for making larger macrocycles because the rigid the circular dichroism (CD) exciton chirality method,
structure having direct connection of pyrrole rings with the supramolecular chirality induction has been suc-
an arene ring would not reduce cyclization efficiency as cessfully used for the absolute configuration determi-
compared to 2,2ꢁ-bipyrrole. Furthermore, photo, redox, nation of chiral substances.7a–d The unique structure
and acid–base functionality intrinsic to the arene moie- of cyclooctapyrroles is potentially effective in sensing
ty can be introduced into the macrocycle. In this con- wide spectrum of chiral substances. X-ray crystallo-
text, we have prepared 2-borylpyrrole 7 quantitatively graphy of O1 indicates figure-eight conformation that
according to the protocol for borylation of aromatic leads to a P, P helical enantiomer and a M, M helical
halides starting from 2-carboethoxy-3,4-dialkylpyrrole enantiomer (figure 1). O1 is undergoing rapid inversion
Scheme 5. Synthesis of dipyrrylarenes by using borylpyrrole 7 and their application to the porphyrin analogue O3.

Helical porphyrin analogues
1155
Figure 1. X-ray diagram of O1 viewed along right axes.
between the M, M form and the P, P form in solu- tive and the (R)-acids positive chirality (table 1). The
tion.19 The CD spectrum is silent for O1, whereas the OH group containing acids, A1–A3, make complete
positive 1st Cotton effect of the bisignate CD signal conversion of O1 to diprotonated species that give clear
band at 644 nm arises upon complexation with (R)-(–)- CD spectra when added 300-fold excess. Also, the posi-
mandelic acid.20 The titration experiment shows that tioning of the 1st Cotton effect and UV-vis absorption
the CD band at 644 nm and the UV-vis band at 647 nm maxima are similar. The lactic acid derivative A4 and
due to both 1:1 and 1:2 complexes take the maxi- the CF3 group containing A11 bind strongly to O1
mum intensity at 50 equiv of (R)-(–)-mandelic acid and easily form tri- and tetraprotonated complexes that
(figure 2a,b). The sign of this induced Cotton effect show characteristic UV-vis absorption band at around
is solely determined by the absolute configuration of 590 nm when present more than 30 molar equiva-
the carboxylic acid thus (S)-(+)-mandelic acid induced lents. Weak binding was observed for simple carboxylic
a mirror image CD spectrum. The ability of sensing acids, A6–A8. This is most likely due to their less acidic
the chirality of carboxylic acids by O1 is remarkable. nature in comparison with the α-hydroxyl acids, A1–
All the (S)-configuration acids examined induce nega- A4. Although 3-phenyllactic acid A4 binds much more
Figure 2. CD (a) and UV-vis (b) spectral changes of O1 (5.9 μM in CH2Cl2) upon
addition of (R)-(–)- or (S)-(+)-mandelic acid (18 mM in MeOH) at 293 K.

1156
Jun-Ichiro Setsune
Table 1. CD and UV-vis spectrometric data for supramolecular chirogenesis upon
complexation of O1 with various chiral carboxylic acids at 298 K in a 1 cm optical
cell.[a]
CD sign (λmax/nm)
UV-vis
(λmax/nm)
ꢀθ/ꢀabs
Ligand
of 1st Cotton effect
(mdeg)[f]
(R)-(−)-A1[b]
(S)-(+)-A1[b]
(R)-(−)-A2[b]
(S)-(+)-A2[b]
(S)-(−)-A3[b]
(S)-(−)-A4[b,d]
(S)-(−)-A5[b]
(R)-(−)-A6[c]
(S)-(+)-A6[c]
(S)-(+)-A7[b,e]
(S)-(+)-A8[c,e]
L-A9[b]
+(644)
–(644)
+(639)
–(639)
–(642)
–(644)
–(611)
+(642)
–(642)
–(644)
–(641)
–(643)
–(622)
+(647)
–(647)
647
647
649
649
647
636
638
642
642
636
641
646
630
642
642
87
81
55
49
60
17
11
21
27
26
6
17
12
19
15
(S)-(−)-A10[c,e]
(R)-(+)-A11[c,d]
(S)-(−)-A11[c,d]
[a] [O1] = 6.5 μM in CH2Cl2. [carboxylic acid]=1.95 mM. [b] in MeOH. [c] in CH2Cl2.
[d] C = 195 μM. [e] C = 9.75 mM. [f]|1st Cotton effect λmax mdeg|/corresponding band
λ
max ꢀabs
H
OH
H
OH
H
OH
H
OH
CO2H
CO2H
CO2H
CO2H
2-hydroxy-
isocaproic acid
3-phenyllactic acid
mandelic acid
hexahydromandelic acid
A4
A3
A1
A2
H
H
H
H
Br
CO2H
CO2H
2-methylbutyric acid
A8
CO2H
CO2H
MeO
2-bromo-
propionic acid
2-phenyl-
propionic acid
2-(6-methoxynaphth-2-yl)-
propionic acid
A5
A6
MeO CF3
CO2H
A7
BOCNH
CO2H
CO2H
CO2H
α-methoxy-α-trifluoro-
methylphenylacetic acid
N-Boc-aspartic acid
perillic acid
A9
A10
A11
strongly than 2-hydroxyisocaproic acid A3 but yields acid complex of P, P heliccal O1 as shown in
smaller intensity CD spectrum, which is consistent scheme 6.
with the substituent bulkiness order effect. The large
size of the naphthyl derivative substituent in A7 is a
possible reason for the weak binding thus suggesting
3.2 Enantioselective helical chirality induction
that O1 is not able to complex with even larger size car- Helical chirality is usually controlled by introducing a
boxylic acids. Surprisingly, the absolute configuration chiral auxiliary to cause the generation of a particular
of the remote chiral centre in A10 can be read out by helical form in diastereomeric excess as described for
O1. This dynamic helical chirality induction depends on O1.21 However, enantioselective induction of helicate
the relative thermodynamic stability of two diastereo- formation with a chiral promoter in the absence of
meric complexes, for example, (S)-(+)-mandelic acid homochiral auxiliary is a challenging research target.
complex of M, M heliccal O1 and (S)-(+)-mandelic O2 was readily metallated by Cu(OAc)2 to give

Helical porphyrin analogues
1157
Scheme 6. Generation of diastereomeric excess of helical chirality with homochiral guest.
mononuclear and dinuclear complexes in 43% and and CD spectra on the basis of the X-ray structure of
50% yield, respectively, and their figure-eight struc- O2Cu2 in the M, M helicity satisfactorily reproduced
tures were characterized by X-ray crystallography the spectra of the HPLC second fraction. Therefore,
(figure 3).22 The helical chirality of these metal complexes the negative 1st Cotton effect was associated with
is fixed and therefore enantiomeric separation of the the M, M helical form. This assignment is consistent
dinuclear complex O2Cu2 was successful by HPLC on with the prediction made by exciton chirality method
a chiral phase. The HPLC first fraction showed a posi- that correlates the sign of the 1st Cotton effect with
tive 1st Cotton effect at 697 nm and the second fraction the coupling dipole direction, clockwise or counter-
showed a negative 1st Cotton effect at the same wave- clockwise, of the electronic transition moments of the
length (figure 4c). These CD spectral features are very neighbouring two chromophores. Transition moment
similar to those of O2 complexed with (R)-(–)- and of the front bisdipyrrin chromophore in the figure-
(S)-(+)-mandelic acid, respectively (figure 4a). There- eight screw of (M, M)-O2Cu2 couples with that in
fore, a particular helical form is favoured when O2 as the backside bisdipyrrin chromophore through counter-
well as O1 is complexed with homochiral carboxylic clockwise rotation and thus negative 1st Cotton effect
acids (scheme 7). TDDFT calculation of the UV-vis is predicted according to the exciton chirality method
Figure 3. X-ray diagram of O2Cu2 viewed along right axes.

1158
Jun-Ichiro Setsune
Figure 4. CD (a) and UV-vis (b) spectral changes of O2 (18 μM) in CH2Cl2 (3 mL)
by adding (S)-(+)-mandelic acid or (R)-(–)-mandelic acid (200 molar equiv) in MeOH
(40 μL). CD (c) and UV-vis (d) spectra of the HPLC fractions of O2Cu2 on a chiral phase.
(figure 5, left).23 Because of the closely related structure
When metallation reaction was done in the pre-
of O1 and O2, M, M helicity induction is suggested for sence of chiral promoter such as (R)-(+)-1-(1-
the (S)-(+)-mandelic acid complex of O1 that displays phenyl)ethylamine, excess of P, P helicity up to 19%
a negative 1st Cotton effect (figure 2a).
ee resulted in the mononuclear O2Cu complex (k1P >
Scheme 7. Generation of diastereomeric excess of helical chirality with homochiral
guest and enantiomeric excess with homochiral promoter (L∗). Rate constants, k1M, k1P,
k2M, and k2P, and equilibrium constants, KM and KP, are shown.

Helical porphyrin analogues
1159
Figure 5. Coupling dipole direction of electronic transition moments of (M, M)-
O2Cu2 (top, left) and (S)-mandelate complex of (P, P)-O3Co2(L)2 (top, right) with
its side view (bottom, right). Predicted M, M helicity of the (S)-mandelate complex of
diprotonated O2 (bottom, left).
k1M) if 800/400/1 ratio of amine/Cu/O2 was used at as the rate (k2M) for the metal insertion into (M, M)-
0◦C. The enantiomeric excess (% ee) could be deter- O2Cu. As the metallation proceeds, (P, P)-O2Cu is
mined by the CD intensity after conversion of the consumed faster, which is consistent with the develop-
product O2Cu complex into O2Cu2. Furthermore, the ment of excess of the M, M helicity for O2Cu. Thus,
same chiral amine accelerated the insertion of the se- 72% ee of M, M helicity was observed for O2Cu at the
cond Cu ion to the P, P form of O2Cu (k2P >k2M).22 final stage of the metallation (table 2, entry 5). These
That is, when a racemic mixture of O2Cu was treated results show that kinetic resolution may be a potential
with (R)-(+)-1-(1-phenyl)ethylamine (10 equiv) and means in preparation of metal porphyrinoids with high
CuCl2•2H2O (5 equiv) in CH2Cl2, ee value of 33% optical purity.
was observed for (P, P)-O2Cu2 in the initial stage of
the metallation (table 2, entry 1), although this reaction
condition does not make remarkable difference between
the rate constants, k1M and k1P, to result in only 2%
3.3 Dynamic helicity change in the metal
porphyrinoids
ee for (P, P)-O2Cu. This means that the rate (k2P) for As described above, O1 and O2 can be induced to
the metal insertion into (P, P)-O2Cu is twice as fast adopt a particular unidirectional helical conformation
Table 2. Conversion of racemic O2Cu to O2Cu2 by CuCl2•2H2O in the presence
of (R)-(+)-1-(1-phenyl)ethylamine at room temperature in CH2Cl2.[a]
CD sign
669 nm
O2Cu
CD sign
697 nm
O2Cu2
ee (%)[b]
O2Cu
ee (%)
O2Cu2
Molar ratio
O2Cu/O2Cu2
Entry
Time (h)
1
2
3
4
5
3
9
12
16
24
–
–
–
–
–
3
+
+
+
+
+
33
29
25
19
6
9/1
6/4
5/5
3/7
1/9
15
25
36
72
[a]
CH2Cl2 solution of O2Cu[b](0.36 μM) was reacted with a molar ratio
(amine/CuCl2•2H2O/O2) 10/5/1.
% ee was determined using |ꢀε583 – ꢀε496| as
an index after conversion to O2Cu2 by Cu(OAc)2•H2O, if necessary

1160
Jun-Ichiro Setsune
preferentially by complexation with homochiral car- take an anti conformation where the N–C–C–N torsion
boxylic acids in CH2Cl2. Such complexes of homochi- angles are 146.6 and 139.1◦, leading to figure eight
ral carboxylic acids are labile and the CD response macrocycle conformation. Two carboxylate ligands are
at around 600 nm has almost gone in MeOH even if on the opposite sides of the macrocycle and close to
cyclooctapyrrole retains its protonated form. This indi- the water ligand at the axial position of the neighbour-
cates that binding interaction supplied mainly by hydro- ing Co atom. One bipyridine unit is not coordinating
gen bondings does not work well in protic media. to Co but their nitrogens are involved in the hydro-
Metal-ligand coordination bondings are generally much gen bonding with the water ligands (N–O distance:
stronger than hydrogen bondings so that helical chi- 2.791 and 2.870 Å). The Co–N(pyridine) bonds (2.358
rality of cyclooctapyrroles would find much wider and 2.367 Å) are much longer than the Co–N(pyrrole)
application if homochiral ligand molecules coordinate bonds (1.965 ∼ 2.121 Å) and tilted from the pyri-
reversibly to cyclooctapyrrole metal complexes. How- dine plane (27.7◦ and 28.3◦). These structural feature
ever, examples of porphyrinoid metal complexes hav- causes reversible cleavage of the Co–N(pyridine) bond-
ing additional ligands are not only limited, but also ing that would be crucial for the helicity change of the
well-defined substitution labile metal complexes of macrocycle. The axial acetate ligands of O3Co2(OAc)2
large porphyrinoids have never been known.24 Further- are readily exchanged with carboxylates of α-hydroxyl
more, although metal insertion is useful for the purpose acids and α-amino acids in water to cause helical chi-
of freezing transiently produced unidirectional helical rality induction in 100% diastereoselectivity in some
chirality of cyclooctapyrrole free base as shown for cases as evidenced by a CD couplet at 550 nm. A typi-
O2Cu2,22,25 it becomes a serious problem if helical cal couplet with a positive Cotton effect at 597 nm and
chirality change responding to the stereochemistry of a negative Cotton effect at 538 nm appeared during
the additional ligand is intended in the framework of the CD titration of O3Co2(OAc)2 (4.98 μM) in CH2Cl2
cyclooctapyrrole metal complexes.
with a mixture of (S)-(+)-mandelic acid (1.99 mM) and
A hybrid macrocycle O3 composed of bipyridines triethylamine (2.40 mM) in CH2Cl2/CH3CN (19/1 v/v)
and dipyrrins gave biscobalt complexes of figure-eight (figure 7). Saturation occurred at ca. 20-fold molar
conformation with k2-carboxylate ligands at the axial equiv of the carboxylate. The product complex was
sites.18 X-ray crystallography of O3Co2(OCOPh)2 isolated and the NMR analysis demonstrated 88%
shows that each hexadentate Co is ligated by dipyrrin diastereomeric excess (de). Because the UV-vis absorp-
nitrogens, a bipyridine nitrogen, k2-benzoate oxygens, tion band of these binuclear CoII complexes at 550 nm
and a water oxygen (figure 6). The 2,2ꢁ-bipyridine units can be associated with the electronic transition of the
Figure 6. X-ray diagram of O3Co2(OCOPh)2 viewed along right axes.

Helical porphyrin analogues
1161
P, P helicity seen in the exciton coupling diagram
in figure 5 (right) according to the exciton chirality
method.23
The ligand exchange is so fast that anionic ligands
can be extracted from water layer. When a two-phase
mixture of O3Co2(OAc)2 in CH2Cl2 and L-threonine
(100-fold molar equiv) with NaOH (30-fold molar
equiv) in water was stirred for 30 min, the reaction was
completed to give O3Co2(Thr)2 in 77% isolated yield.
The 1H NMR spectrum showed that a single diastereo-
mer was generated. In fact, L- and D-threonine gene-
rated mirror image CD spectra with the highest CD
intensity among amino acids as seen in table 3 where
the sign and wavelength of the 1st Cotton effect with
its |ꢀθ| value are listed for 19 L-amino acids. This
strict stereo control would be ascribed to two chiral
centres present at the α- and β-carbon of threonine.
The induced CD intensity is sensitive to the nature of
amino acids. Amino acids of an aryl side chain (Phe,
Tyr, Trp) induced strong CD intensity as much as Thr
Figure 7. CD titration of O3Co2(OAc)2 (4.98 μM) in
CH2Cl2 with (S)-(+)-mandelic acid (1.99 mM) and triethyl-
amine (2.40 mM) in CH2Cl2/CH3CN (19/1). Inset: A titra-
tion curve of the CD intensity vs. added molar equiv of the
carboxylate.
dipyrrin chromophore, their exciton coupling should be
responsible for the CD couplet at around 550 nm. Thus,
a positive couplet induced by (S)-(+)-mandelate means
Table 3. UV-vis and CD data of Co complexes ligated by amino acid
anions.[a]
O2CCH(NH2)R*
AcO
OH2
Co
OAc
HO2CCH(NH2)R*
NaOH
H2O
Co
*R(H2N)HCCO2
Co
Co
OH2
CH2Cl2 / H2O
H2O
UV-vis
λmax(εrel)/nm
2nd CE/1st CE
sign(λmax)/nm
Ligand
|ꢀθ[b]| /mdeg
Ala
Leu
Ile
551 (1.18)
551 (1.30)
551 (1.27)
551 (1.19)
551 (1.16)
552 (1.12)
552 (1.04)
547 (0.95)
552 (1.19)
552 (1.15)
552 (1.24)
552 (1.02)
552 (1.17)
551 (0.59)
552 (0.93)
552 (0.98)
552 (0.90)
552 (0.92)
551 (1.00)
552 (0.86)
–(540)/+(594)
–(535)/+(587)
–(533)/+(581)
–(533)/+(581)
+(538)/–(594)
–(538)/+(594)
+(537)/–(592)
–(518)/+(558)
–(539)/+(591)
–(540)/+(592)
–(536)/+(590)
–(538)/+(591)
–(537)/+(590)
n.d.
31
47
22
10
126
122
32
25
42
93
117
123
116
0
25
3
10
0
7
7
Val
Thr
D-Thr
Ser
Cys
Met
Pro
Phe
Tyr
Trp
His
Arg
Lys
Gln
Glu
Asn
Asp
–(537)/+(592)
–(537)/+(595)
–(540)/+(598)
n.d.
+(540)/–(593)
–(548)/+(599)
[a] Data were taken in CH2Cl2 containing O3Co2(OAc)2 (4.7 μM) after
stirring for 30 min with aqueous solution of amino acids (0.47 mM; 100-
fold molar equiv) and NaOH (0.14 mM). [b] the CD intensity |ꢀθ| is the
difference value between the 1st Cotton and the 2nd Cotton effect |θ1st
– θ2nd|.

1162
Jun-Ichiro Setsune
Scheme 8. Plausible ligand substitution pathway with helicity change.
to suggest very high stereo control. On the other hand, 4. Conclusions
amino acids of an alkyl side chain usually showed
weaker CD intensity. When amino acid’s side chain The unique figure-eight conformation of cyclooc-
contains strongly polar functionality, the CD induction tapyrroles is a potentially useful scaffold for developing
is negligibly small. Since the size of OH, CH3, and molecular tools for chirality science. Properly designed
NH2 groups at the α-carbon of carboxylates fits inside expanded porphyrins for application to chirality induc-
the crevice surrounded by the walls of pyridine rings, tion and chirality sensing are described here. Binding
the bulkier substituent at the α-carbon hits or circum- chiral carboxylic acids to O1 through multiple hydro-
vents those walls depending on the helical handed- gen bondings is the basis for generating helical chirality
ness of the macrocycle. This explains universal rela- that can be detected by CD response at visible region.
tionship between a positive 1st Cotton effect at around Remarkable read-out accuracy of O1 for the absolute
590 nm and the (S)-configuration at the α-position of configuration of carboxylic acids was demonstrated.
carboxylic acids. Thr, and Ser have a hydroxyl group at While those dynamic chirality transfer from carboxy-
the β-carbon and Asn has an amide oxygen or nitrogen late anions to protonated porphyrioids was weakened in
at the γ -carbon. If these remote functionalities favour protic media, helicity is memorized in the form of metal
the position inside macrocycle crevice to participate in complexes. Study on the Cu complexes of O2 eluci-
the hydrogen bonding interaction with axial ligand sit- dated relationship between the sign of the CD 1st Cotton
ting side by side at the next metal site, it would be effect and the helical handedness. Furthermore, enan-
responsible for their opposite CD sign.
tiomeric excess of the Cu complex of O2 was induced
As revealed by X-ray, the bipyridine nitrogens are by chiral promoter in the metallation process. Finally,
anchored to Co directly through the weak coordination Co complexes of O3 with carboxylate ligands were iso-
bonding and indirectly through the hydrogen bonding lated to show that the chirality of the axial ligands has
to the axial water ligands. It is reasonably assumed that a great influence on the helical chirality of the macro-
the added carboxylate anions would replace the axial cycle. These Co complexes underwent ligand exchange
water ligands with concomitant cleavage of the weakly with concomitant helicity change that is enabled by
coordinating bipyridine nitrogens of the C2-symmetric reversible on-off coordination of the bipyridine nitro-
bis(aquo)bis(k2carboxylato)bisCo complex to generate gens within the macrocycle. Such dynamic feature of
a D2-symmetric intermediate of dual six-coordinate the Co complex enabled to pick up amino acid anions in
bis(k2-carboxylato)(dipyrrinato)Co coordination mode water and showed characteristic CD response depend-
as depicted in scheme 8. The bipyridine units of the ing on the amino acid. Structural design of expanded
latter are free to make helicity change of the macrocycle porphyrin analogues warrants further development of
for a favoured helical screw.
functional materials for chiral science.

Helical porphyrin analogues
1163
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