Stereochemically stable double-helicate dinuclear complexes of bis(dipyrromethene)s: A chiroptical study

Article abstract of DOI:10.1021/ja0500613

Helical zinc(II) complexes of bis(dipyrromethene)s bearing homochiral amide substituents were synthesized. Analysis of the products by chiral HPLC showed two diastereomeric major products and showed that dipyrromethene double-nuclear helicates are stereoc

Full text of DOI:10.1021/ja0500613

Published on Web 03/30/2005
Stereochemically Stable Double-Helicate Dinuclear Complexes of
Bis(dipyrromethene)s: A Chiroptical Study
Tabitha E. Wood,† Nathan D. Dalgleish,† Erin D. Power,† Alison Thompson,*,† Xiaoming Chen,‡ and
Yoshio Okamoto‡
Department of Chemistry, Dalhousie UniVersity, Halifax, NoVa Scotia, B3H 4J3, Canada, and
EcoTopia Science Institute, Nagoya UniVersity, Furo-cho, Chikusa-ku, Nagoya, Japan
Received January 5, 2005; E-mail: alison.thompson@dal.ca
Dipyrromethenes are fully conjugated, planar bipyrrolic units that
have attracted recent attention as ligands in supramolecular self-
assembly.1 N-Deprotonated dipyrromethenes act as ligands on
cationic metal centers. The resulting complexes are neutral and can
often be purified by chromatography in contrast to bipyridyl and
catechol complexes that bear the charge of the metal cation
involved.2 Recent reports using dipyrromethenes with appendages
containing acetylenyl, thiol, or pyridyl functionality have shown
rod-like, polymeric, hexagonal, and other crystalline frameworks
to form via self-assembly.3
Carefully designed bis(dipyrromethene)s self-assemble into
Figure 1. Symmetric zinc(II) bis(dipyrromethene) helicate.
discrete complexes of helical mononuclear, dinuclear, and trinuclear
architectures,1,4 depending on the length of the spacer that joins
the two dipyrromethene units. As part of our work with chiral bis-
(dipyrromethene) complexes, we herein report the first synthesis,
isolation, and chiroptical studies of enantiopure bis(dipyrromethene)
ligands and their stereochemically stable, double-helicate com-
plexes.
Scheme 1. Synthesis of the Zinc(II) Bis(dipyrromethene) Helicates
Bearing Homochiral Amide Substituents
Methylene-, ethylene-, and propylene-linked bis(dipyrromethene)s
form, with divalent metal cations, helical complexes with a
structural formula L2M2, illustrated by the complexes 11a and 25 in
Figure 1. Until now, only racemic mixtures of enantiomeric helicates
have been formed, as identified by X-ray crystallography1a and
confirmed by chiral lanthanide shift 1H NMR spectroscopy.6 Neither
of these techniques enabled the stereochemical stability of the helix
to be determined. The M and P helical zinc(II) complexes formed
from homochiral bis(dipyrromethene) ligands are related to each
other as diastereoisomers, and therefore the complexation process
is potentially diastereoselective. However, separation of these
diastereomeric helices necessitates stereochemical stability, that is,
the absence of helix sense interconversion. Stereogenic centers have
previously been used as chiral auxiliaries to induce helix formation
in a particular sense (i.e., helical diastereoselectivity).7 Reichardt
et al. have reported on a number of helical polymethine dyes,8 and
Lightner et al. have shown that bilirubin and other dipyrrinone
structures adopt either M or P helical conformations according to
the absolute stereochemistry of remote stereogenic centers.9 Simi-
larly, Mizutani et al. have shown that zinc(II) bilinones may be
formed diastereoselectively through the induction of helicity by the
point chirality in homochiral precursors.10 Although homochiral
dipyrromethene ligands have been used to form optically active
fluorescent boron dipyrromethene (BODIPY) dyes,11 there are no
reports of such homochiral ligands being used in the formation of
helical complexes. To the best of our knowledge, homochiral bis-
(dipyrromethene) ligands and/or the corresponding complexes have
not previously been reported.
To establish the stereochemical stability of double-helical di-
nuclear bis(dipyrromethene) complexes and to examine the potential
for diastereoselective helicate formation, we have synthesized bis-
(dipyrromethene) ligands that contain chiral amide substituents at
the two termini of the linear tetrapyrrolic molecules (Scheme 1).
Benzyl 3,5-dimethyl-4-propionic acid-pyrrole-2-carboxylate (4) was
prepared by the hydrolysis of benzyl 4-(2′-methoxycarbonylethyl)-
3,5-dimethylpyrrole-2-carboxylate (3)12 using lithium hydroxide.
The incorporation of the chiral substituent into the ligand was
achieved by coupling a homochiral amine (1-phenylethylamine)
with 4 using O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium
hexafluorophosphate (HBTU). The chiral amide-substituted pyrrole
(5) was then coupled to 2,2′,4,4′-tetramethyl-5,5′-diformyl-3,3′-
dipyrromethane (6)1b to form the hydrobromide salt of the bis-
(dipyrromethene) (7a and 7b). The zinc(II) complexes (8a and 8b)
were obtained by stirring a solution of the bis(dipyrromethene)
ligands with zinc acetate and sodium acetate, followed by extraction
and routine workup and full characterization.
† Dalhousie University.
‡ Nagoya University.
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10.1021/ja0500613 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
concentrations used in the CD studies (HPLC fractions) and the
fact that unresolved mixtures were used to measure the required
molar absorptivities.
These results represent the first diastereoselective dipyrromethene
complexation reactions. Additionally, we have shown that double-
helicate dinuclear bis(dipyrromethene) complexes are stereochemi-
cally stable. This indicates that stereochemical inversion around
the zinc center is not taking place. Having shown that diastereo-
selective bis(dipyrromethene) complexes reactions are feasible and
that the M and P helices of the complexes are isolable, our current
work is being directed toward improving the diastereoselectivity
of dipyrromethene complexation reactions by expanding the
repertoire of homochiral dipyrromethene ligands for double-helicate
dinuclear bis(dipyrromethene) complexes.
Figure 2. CD spectrum for the unresolved mixture of 8a.
Figure 3. (a) UV-vis trace for the chiral HPLC analysis of 8a. (b) CD
Acknowledgment. Financial support for this research was
provided by the Natural Sciences and Engineering Research Council
(NSERC) of Canada, the Canada Foundation for Innovation, the
Nova Scotia Research Innovation Trust, Dalhousie University, and
the Killam Trusts. We thank Ian Comeau and Jack Shyh-Jye Lan
(Dalhousie University) for the preparation of 2 and assistance with
acquiring some of the CD data, respectively, and Professor M. M.
Green (Polytechnic University, New York) for helpful discussions
during the preparation of this manuscript.
spectra for the two isomers (A and B) resolved by chiral HPLC.
Circular dichroism (CD) spectra were recorded for samples 8a
and 8b (Figure 2). In each case, the presence of a measurable
ellipticity in the unresolved samples suggested that the reactions
had indeed proceeded with some diastereoselectivity. Encourag-
ingly, the two enantiomeric ligands (8a and 8b) gave rise to zinc
complexes that had opposite circular dichroisms, suggesting that
the R and S chiral centers were inducing opposite senses of helicity,
1
as anticipated. However, H and 13C NMR spectroscopic studies
Supporting Information Available: Procedures for the preparation
of 4-8. This material is available free of charge via the Internet at
http://pubs.acs.org.
indicated an approximate 1:1 mixture of diastereomeric helicates
in each case. The CD is directly related to the molar absorptivity
of the complexes, and this was measured to be in the order of 106
L mol-1 dm-1. Consequently, a small diastereomeric excess of one
helicate over the other would manifest itself as a relatively large
CD activity.
Chiral HPLC analysis13 of 8a and 8b showed two major peaks
at 534 nm (Figure 3a) that displayed opposite circular dichroisms
both using an internal HPLC-CD detector operating at 220 nm and
then following isolation of the two major peaks and full CD analysis
(Figure 3b). Isomer A shows a positive Cotton effect at 470 nm
and a negative Cotton effect at 520 nm (with exciton coupling),
leading to its tentative assignment as the M helix and isomer B as
the P helix.14
To eliminate the possibility that the CD activity was a result of
induced exciton coupling14 between the phenyl ring of the homo-
chiral amide substituent and the dipyrromethene units, an achiral
bis(dipyrromethene) ligand was complexed to form the per-alkyl
bis(dipyrromethene) zinc(II) complex 2 (Figure 1). Chiral HPLC
analysis of 2 again resolved two major peaks with opposing CD
couplets. In the absence of other chromophores in 2, the observed
chiroptical properties of the compounds must arise from the
stereochemically stable helical, and thus chiral, dipyrromethene units
within the complex. Using the molar ellipticities of the two chiral
HPLC-resolved zinc(II) bis(dipyrromethene) helices A and B, the
total molar ellipticity of the unresolved mixture, and the molar
absorptivities of the unresolved mixtures, we calculated diastereo-
meric excesses for each of the mixtures 8a and 8b. The calculated
diastereomeric excesses were low: 8% for 8a and 2% for 8b. As
enantiomeric homochiral ligands 7a and 7b were used to prepare
the mixtures 8a and 8b, respectively, the diastereomeric excesses
should be equal for the two samples. The observed discrepancy
between these two values is presumably a consequence of the low
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