Highly diastereoselective templated complexation of dipyrromethenes

Article abstract of DOI:10.1021/ol052044o

(Chemical Equation Presented) Bis(dipyrromethene)s with relatively long spacers (>5 atoms) form helical monomeric complexes as the two binding units of the bis(dipyrromethene) chelate around the same tetrahedrally coordinated metal ion. Herein we report t

Full text of DOI:10.1021/ol052044o

ORGANIC
LETTERS
2005
Vol. 7, No. 21
4773-4775
Highly Diastereoselective Templated
Complexation of Dipyrromethenes
Adeeb Al-Sheikh-Ali, Kyle S. Cameron, T. Stanley Cameron,†
Katherine N. Robertson,† and Alison Thompson*
Department of Chemistry, Dalhousie UniVersity, Halifax,
NoVa Scotia, B3H 4J3, Canada
alison.thompson@dal.ca
Received August 24, 2005
ABSTRACT
Bis(dipyrromethene)s with relatively long spacers (>5 atoms) form helical monomeric complexes as the two binding units of the
bis(dipyrromethene) chelate around the same tetrahedrally coordinated metal ion. Herein we report the first highly diastereoselective mononuclear
helicate-forming complexation reactions of bis(dipyrromethene)s using homochiral binol and tartrate motifs which serve as both linkers and
asymmetric templates.
Dipyrromethenes (dipyrrins) give monoanionic ligands that
form neutral complexes with various metal ions.1,2 Bis-
(dipyrromethene)s with short linkers form helical double-
stranded dinuclear complexes from the self-assembly of two
bis(dipyrromethene)s and two tetrahedrally coordinated metal
ions.3-5 Conversely, bis(dipyrromethene)s with relatively
long spacers (>5 atoms) form helical monomeric complexes
as a result of the two binding units of the bis(dipyrromethene)
chelating around the same tetrahedrally coordinated metal
ion.6 Chiral auxiliaries and templates have been reported to
effect helical bias and enantioselectivity in supramolecular,7
polymer,8,9 and complexation chemistry.10,11 The template
directs the forming helicity by virtue of the stereochemical
effects of its absolute configuration. For example, remote
stereogenic centers have been shown to induce diastereose-
lective helix formation in bilirubins and zinc bilinones.12-14
We have recently demonstrated the stereochemical stability
of dinuclear double-helical bis(dipyrromethene)s zinc(II)
complexes using novel ligands appended with homochiral
amides, although the observed diastereoselectivity of com-
plexation was very low (<10%).15
The first report16 of single enantiomers of bis(dipyr-
romethene) complexes came from Bro¨ring et al., who used
MPLC to separate the two helicates of 2,2′-bis(dipyr-
(7) Tang, K.; Green, M. M.; Cheon, K. S.; Selinger, J. V.; Garetz, B. A.
J. Am. Chem. Soc. 2003, 125, 7313-7323.
† To whom queries relating to the X-ray crystallographic data should be
directed.
(1) Paine, J. B., III In The Porphyrins; Dolphin, D., Ed.; Academic
Press: New York, 1978; Vol. I, Chapter 4.
(2) Taylor, E. C.; Jones, R. A. Pyrroles; John Wiley & Sons: New York,
1990.
(8) Chow, H.-F.; Wan, C.-W. J. Org. Chem. 2001, 66, 5042-5047.
(9) Gin, M. S.; Yokozawa, T.; Prince, R. B.; Moore, J. S. J. Am. Chem.
Soc. 1999, 121, 2643-2644.
(10) Woods, C. R.; Benaglia, M.; Cozzi, F.; Siegel, J. S. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1830-1833.
(11) Yashima, E.; Maeda, K.; Okamoto, Y. Nature 1999, 399, 449-
451.
(12) Yagi, S.; Morinaga, T.; Nomura, T.; Takagishi, T.; Mizutani, T.;
Kitagawa, S.; Ogoshi, H. J. Org. Chem. 2001, 66, 3848-3853.
(13) Boiadjiev, S. E.; Lightner, D. A. Tetrahedron: Asymmetry 2004,
15, 3301-3305.
(3) Dolphin, D.; Harris, R. L. N.; Huppatz, J. L.; Johnson, A. W.; Kay,
I. T. J. Chem. Soc. (C) 1966, 30-40.
(4) Sheldrick, W. S.; Engel, J. Chem. Commun. 1980, 5-6.
(5) Struckmeier, G.; Thewalt, U.; Fuhrhop, J.-H. J. Am. Chem. Soc. 1976,
98, 278-279.
(6) Thompson, A.; Dolphin, D. J. Org. Chem. 2000, 65, 7870-7877.
10.1021/ol052044o CCC: $30.25
© 2005 American Chemical Society
Published on Web 09/23/2005

romethene) nickel(II) complexes. The resolved enantiomers
showed complimentary Cotton effects in their CD spectra,
and the M and P helices were thus assigned. Although
dipyrromethenes bearing homochiral auxiliaries have been
used to prepare optically active fluorescent dipyrromethene-
BF2 (BODIPY) dyes,17,18 such ligands have not been used
in the formation of helicates, apart from our own report.15
Herein we report the first highly diastereoselective mono-
nuclear helicate-forming complexation reactions of bis-
(dipyrromethene)s incorporating homochiral binol and tartrate
motifs, which serve as both linkers and asymmetric tem-
plates.
Scheme 2. Diastereoselective Synthesis of 6 and 7
To examine the potential for diastereoselective mono-
nuclear bis(dipyrromethene) helicate formation, bis(dipyr-
romethene)s containing homochiral binol19-21 and tartrate
linkers were prepared (Scheme 1). Hydrolysis of methyl ester
Scheme 1. Synthesis of 4 and 5
and the use of mass spectrometry confirmed the formation
of mononuclear complexes, rather than dimers or oligomers.
According to 1H NMR spectroscopic analysis excellent
diastereoselectivities were observed for the complexation
reactions; only a single diastereoisomer of 6 had formed and
two diastereoisomers of 7 had formed in a 9:1 ratio
(determined by integration of the signals corresponding to
the diastereotopic CH2 group). These are the first examples
of helical mononuclear dipyrromethene complexes formed
in a stereoselective manner, and the first efficient diastereo-
selective dipyrromethene complexation reactions.
The two reaction mixtures containing 6 and 7 were
analyzed by chiral HPLC.23 Using a Pirkle column, Bro¨ring
has previously separated nickel(II) helicates of 2,2′-bis-
(dipyrromethene)s meso-substituted with aryl groups, ex-
ploiting stereocontrolled aryl-aryl interactions to enable
resolution of the two helical enantiomers. The dipyr-
romethenes reported herein are not meso-substituted, and
resolution of diastereoisomers was not observed when using
a wide range24 of Pirkle-type columns. As reported previ-
ously15 CHIRALPAK columns give satisfactory resolution
of dinuclear double-helicate bis(dipyrromethene) complexes.
It was gratifying to discover that excellent resolution was
observed for 6 and 7 with CHIRALPAK IA (amylose tris-
(3,5-dimethylphenylcarbamate) immobilized on 5 µm silica
gel). Thus, the reaction mixture containing 7 showed a
diastereomeric excess of 89% by chiral HPLC and that
containing 6 showed only trace quantities of the minor
diastereoisomer (Supporting Information), confirming our
conclusions drawn from NMR spectroscopy.
1,22 followed by coupling of 2 equiv of the resultant
carboxylic acid 2 with (R)-binol using DCC and DMAP gave
the corresponding (R)-binol-linked bis(pyrrole). Hydro-
genolysis of the benzyl esters, followed by treatment with 2
equiv of 4-ethyl-2-formyl-3,5-dimethylpyrrole (3) gave the
required bis(dipyrromethene) 4 in 72% over four steps.
Similarly, the (R,R)-tartrate-linked bis(dipyrromethene) 5 was
prepared in 73% over four steps.
Bis(dipyrromethene) hydrobromide salts 4 and 5 were
reacted with an excess of zinc acetate under standard
complexation conditions15 in the presence of sodium acetate
(Scheme 2). In both cases, excellent yields were obtained
(14) Mizutani, T.; Yagi, S.; Morinaga, T.; Nomura, T.; Takagishi, T.;
Kitagawa, S.; Ogoshi, H. J. Am. Chem. Soc. 1999, 121, 754-759.
(15) Wood, T. E.; Dalgleish, N. D.; Power, E. D.; Thompson, A.; Chen,
X.; Okamoto, Y. J. Am. Chem. Soc. 2005, 127, 5740-5741.
(16) Bro¨ring, M.; Brandt, C. D.; Lex, J.; Humpf, H.-U.; Bley-Escrich,
J.; Gisselbrecht, J.-P. Eur. J. Inorg. Chem. 2001.
Figure 1 shows the CD spectra of the ligand 4 and complex
6. As expected, the binol moiety dominates the CD spectra
in the <250 nm region, and the dipyrromethene conjugate
absorbs in the 400-600 nm region. The signs of the Cotton
effects at 470 and 510 nm confirm the M helix to be the
diastereoisomer formed.16 The CD spectrum of the mixture
(17) Beer, G.; Daub, J.; Rurack, K. Chem. Commun. 2001, 1138-1139.
(18) Gossauer, A.; Nydegger, F.; Kiss, T.; Sleziak, R.; Stoeckli-Evans,
H. J. Am. Chem. Soc. 2004, 126, 1772-1780.
(19) Lu¨tzen, A.; Hapke, M.; Griep-Raming, J.; Haase, D.; Saak, W.
Angew. Chem., Int. Ed. 2002, 41, 2086-2089.
(23) Chiralpak IA column (25 × 4.6 mm2), CHCl3:MeOH (98:2), 0.5
mL/min.
(24) Whelk-O 1, ULMO, DACH, â-Gem, R-Burke 2, Pirkle 1-J,
Phenylglycine, Leucine.
(20) Cui, Y.; Ngo, H. L.; Lin, W. Chem. Commun. 2003, 1388-1389.
(21) Jiang, H.; Hu, A.; Lin, W. Chem. Commun. 2003, 96-97.
(22) Paine, J. B., III; Dolphin, D. J. Org. Chem. 1985, 50, 5598-5604.
4774
Org. Lett., Vol. 7, No. 21, 2005

Figure 1. CD spectra for ligand 4 and zinc complex 6.
containing 7 (89% de) shows that the M helix of 7 dominates,
as a consequence of the (R,R)-tartrate asymmetric linker
(Supporting Information). For both series, the ligands and
the complexes exhibit significant molar ellipticity, with the
same sense, and the values for the complexes are much
greater than those for the ligands. It is assumed that the
activity exhibited by the ligands arises from a preferred
helical conformation as the asymmetric linkers interact with
the dipyrromethene moieties; this preferred conformation is
then locked in place upon complexation. The molar ellipticity
determined for the essentially pure M helix 6 will be useful
in estimating the diastereomeric excess of future mononuclear
bis(dipyrromethene) complexes by analysis of CD spectra.
Further verification of the helical sense and structure of 6
was provided by an X-ray structure (Figure 2a and Support-
ing Information) of a crystal grown from a solution of
chloroform layered with methanol. Although refinement was
unsatisfactory, the absolute configuration of R-binol was
confirmed and M helicity was observed for the dipyr-
romethene complex. Conformational analysis of the M and
P helices of 625 predicted the M helix to be 25 kJ mol-1
more stable than the corresponding P helix, supporting the
observed >99% diastereoselectivity in favor of the M helix.
The energy-minimized structure is shown in Figure 2b and
reveals a distorted tetrahedral zinc(II) center, presumably
necessary to accommodate planarity in both the binol and
dipyrromethene conjugated systems; this is also observed in
the X-ray structure.
Figure 2. (a) ORTEP diagram of 6 (hydrogen atoms omitted). (b)
Minimized structure of 6 (hydrogen atoms omitted).
licates. The synthesis is amenable to scale-up and all starting
materials are readily available. The molar ellipticity for a
helically pure mononuclear dipyrromethene complex has
been established, and chiral HPLC conditions suitable for
the resolution of mononuclear dipyrromethene complexes
have been determined. Our current research is directed
toward examining the scope of the binol and tartrate skeletons
as asymmetric linkers in other dipyrromethene complexes,
and extending the work to include oligomeric and polymeric
helicates.
Acknowledgment. Support for this research was provided
by the Natural Sciences and Engineering Research Council
(NSERC) of Canada, Dalhousie University, the Canada
Foundation for Innovation and the Nova Scotia Research and
Innovation Trust. We thank Mr. C. S. Beshara and Ms. T.
E. Wood for help with the computational work and collection
of the CD data, respectively.
In summary we have developed the first efficient diaste-
reoselective complexation of dipyrromethenes, forming
mononuclear bis(dipyrromethene) helicates. The asymmetry
is induced by a homochiral auxiliary that acts as both linker
and stereochemical template. The observed diastereoselec-
tivity is excellent with the binol-linked bis(dipyrromethene)
giving rise to highly diastereomerically pure dipyrromethene
helicate. This is the first report of a synthesis of highly
diastereomerically, and optically, pure dipyrromethene he-
Supporting Information Available: Preparative proce-
dures and characterization data for 2 and 4-7. This material
is available free of charge via the Internet at http://pubs.acs.org.
(25) Accelrys MS Modeling 3.0 geometric optimization with GGA-
BYLP/dzdp.
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