Asymmetric synthesis of mono- and dinuclear bis(dipyrrinato) complexes

Article abstract of DOI:10.1021/jo070569j

(Chemical Equation Presented) The diastereoselective syntheses of Zn(II) bis(dipyrrinato) helicates is reported, involving ligands templated by the incorporation of homochiral binol within the linker joining the two dipyrrinato units. The most diastereose

Full text of DOI:10.1021/jo070569j

Asymmetric Synthesis of Mono- and Dinuclear Bis(dipyrrinato)
Complexes
Adeeb Al-Sheikh Ali,† Ronald E. Benson,‡ Sascha Blumentritt,§ T. Stanley Cameron,†
Anthony Linden,§ David Wolstenholme,†,§ and Alison Thompson*,†
Department of Chemistry, Dalhousie UniVersity, Halifax, NoVa Scotia, B3H 4J3, Canada, Rigaku Americas
Corp, 9009 New Trails DriVe, The Woodlands, Texas 77381, and Institute of Organic Chemistry,
UniVersity of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
alison.thompson@dal.ca
ReceiVed March 23, 2007
The diastereoselective syntheses of Zn(II) bis(dipyrrinato) helicates is reported, involving ligands templated
by the incorporation of homochiral binol within the linker joining the two dipyrrinato units. The most
diastereoselective formation of dinuclear bis(dipyrrinato) helicates to date is reported. The formation of
either mononuclear or dinuclear helicates can be tuned by varying the length of the linker between the
dipyrrinato units and by varying the complexation procedure. The neutral dipyrrinato helicates were
readily analyzed by HPLC to ascertain diastereoselectivity, and circular dichroism studies revealed the
helical nature of the complexes. The molar ellipticities of the helicates produced by diastereoselective
complexation are very large in the visible region and typically correspond to binol moieties in the UV
region. Extensive X-ray crystallographic investigations further confirmed the helicity of the mononuclear
Zn(II) helicates and identified significant interlayer displacement and bending within crystals.
Introduction
Metal-ion assisted self-assembly is a useful strategy for the
preparation of helical architectures, and polybipyridyl ligands
have been used extensively for this purpose.1-3 Being neutral,
bipyridyl ligands generate complexes bearing the charge of the
metal ion to which they are coordinated. In contrast, dipyrrins
(dipyrromethenes)4 (Figure 1) give monoanionic, planar, fully
FIGURE 1. Skeletal dipyrrin and 2,2′-bis(dipyrrin).
conjugated bidentate ligands for chelation with metal ions5,6 and
with +BR2. Indeed, +BF2 complexes of dipyrrins constitute the
fluorescent BODIPY dyes extensively used as probes and
sensors.7 Neutral complexes of dipyrrins can often be purified
by flash chromatography and analyzed by HPLC.8-11 Dipyrrins,
* To whom correspondence should be addressed. Fax: 1-902-494-1310.
Tel: 1-902-494-6421.
† Dalhousie University.
‡ Rigaku Americas Corp.
§ University of Zurich.
(5) Yang, L.; Zhang, Y.; Yang, G.; Chen, Q.; Ma, J. S. Dyes Pigm. 2004,
62, 27-33.
(6) Halper, S. R.; Cohen, S. M. Inorg. Chem. 2005, 44, 486-488.
(7) Haughland, R. P. Handbook of Fluorescent Probes and Research
Chemicals, 10th ed.; Molecular Probes: Eugene, OR, 2006.
(8) Wood, T. E.; Ross, A. C.; Dalgleish, N. D.; Power, E. D.; Thompson,
A.; Chen, X.; Okamoto, Y. J. Org. Chem. 2005, 70, 9967-9974.
(1) Lehn, J.-M. Supramolecular Chemistry Concepts and PerspectiVes;
VCH: Weinheim, Germany, 1995.
(2) Lou, B.-Y.; Wang, R.-H.; Yuan, D.-Q.; Wu, B.-L.; Jiang, F.-L.; Hong,
M.-C. Inorg. Chem. Commun. 2005, 8, 971-974.
(3) Cui, Y.; Ngo, H. L.; Lin, W. Chem. Commun. 2003, 1388-1389.
(4) Wood, T. E.; Thompson, A. Chem. ReV. 2007, 107, 1831-1861.
10.1021/jo070569j CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/27/2007
J. Org. Chem. 2007, 72, 4947-4952
4947

Ali et al.
FIGURE 2. Templated synthesis of Zn(II) bis(dipyrrinato) complexes.
including highly functionalized derivatives, are readily prepared
from the corresponding pyrrole(s) and can usually be stored
indefinitely as their crystalline hydrobromide salts.12
linker to act as a chiral template for complexation; following a
preliminary communication,9 full results of using binol as a
homochiral templating unit are hereby reported.
The nuclearity and pitch of helicates formed using 1,1′- and
2,2′-bis(dipyrrin)s4 is dependent upon the length and nature of
the linker joining the two dipyrrinato units, as well as the
coordination geometry requirements of the metal ion.13 Bro¨ring
separated nickel(II) 2,2′-bis(dipyrrinato) helicates using MPLC,
thereby demonstrating the stereochemical stability of the heli-
cates.11 Appending chirality onto the bis(dipyrrin) potentially
gives rise to diastereoisomeric helicates and thus the opportunity
for asymmetric complexation. We previously reported the first
synthesis of dinuclear zinc(II) bis(dipyrrinato) helicates featuring
bis(dipyrrins)s bearing pendent homochiral amides and esters.8,14
The CD-spectra of the reaction mixtures for complexation
showed measurable ellipticities, indicating that the complexation
had occurred diastereoselectivity. However, the extent of
diastereoselectivity was very low (<10%), as determined using
NMR spectroscopy. The inclusion of a homochiral moiety within
the linker joining two dipyrrin units provides potential for the
Results and Discussion
To examine the potential for templated diastereoselective
complexation of bis(dipyrrin)s, a homochiral binol moiety was
incorporated into the linker joining two dipyrrin units, and three
such ligands were synthesized with varying linker length (Figure
2). Hydrolysis of the Knorr-type pyrrole carboxylates 1-3,
followed by coupling of the resultant carboxylic acids 4-6 with
(R)-binol gave the dipyrroles 7-9. Although coupling in the
presence of DCC and DMAP gave good yields of 8 and 9, the
purification of the bipyrroles was extremely tedious, owing to
the presence of dicyclohexylurea as byproduct, and required
repeated flash chromatography. An alternative coupling proce-
dure involving TFAA15 gave excellent yields and required only
a simple isolation procedure; consequently, this coupling strategy
was used for the preparation of 7. Hydrogenative debenzylation
of 7-9, followed by acid-catalyzed decarboxylation, gave the
corresponding R-free dipyrroles which were condensed in-situ
with 4-ethyl-2-formyl-3,5-dimethyl-pyrrole (10) to furnish the
required bis(dipyrrin)s as their hydrobromide salts 11-13. The
enantiomeric bis(dipyrrin) (14) of the ethanoate derivative 12
was prepared using (S)-binol.
(9) Al-Sheikh-Ali, A.; Cameron, K. S.; Cameron, T. S.; Robertson, K.
N.; Thompson, A. Org. Lett. 2005, 7, 4773-4775.
(10) Thompson, A.; Rettig, S. J.; Dolphin, D. Chem. Commun. 1999,
631-632.
(11) Bro¨ring, M.; Brandt, C. D.; Lex, J.; Humpf, H.-U.; Bley-Escrich,
J.; Gisselbrecht, J.-P. Eur. J. Inorg. Chem. 2001, 2549-2556.
(12) Paine, J. B., III. In The Porphyrins; Dolphin, D., Ed.; Academic
Press: New York, 1978; Vol. I, Chapter 4.
(13) Thompson, A.; Dolphin, D. J. Org. Chem. 2000, 65, 7870-7877.
(14) Wood, T. E.; Dalgleish, N. D.; Power, E. D.; Thompson, A.; Chen,
X.; Okamoto, Y. J. Am. Chem. Soc. 2005, 127, 5740-5741.
(15) Micheli, F.; Di, Fabio, R.; Cavanni, P.; Rimland, J. M.; Capelli, A.
M.; Chiamulera, C.; Corsi, M.; Corti, C.; Donati, D.; Feriani, A.; Ferraguti,
F.; Maffeis, M.; Missio, A.; Ratti, E.; Paio, A.; Pachera, R.; Quartaroli,
M.; Reggiani, A.; Sabbatini, F. M.; Trist, D. G.; Ugolini, A.; Vitulli, G.
Bioorg. Med. Chem. 2003, 11, 171-183.
4948 J. Org. Chem., Vol. 72, No. 13, 2007

Mono- and Dinuclear Bis(dipyrrinato) Complexes
FIGURE 4. Molar ellipticity for Zn(II) helicates of 12 (R-binol
derived) and 14 (S-binol derived), CH3OH/CHCl3 (98:2), λ474nm
ꢀ 124000 L mol-1 dm-1; [Θ]511nm -4.5 × 106 deg cm2 dmol-1 for the
S-derived complex.
ellipticity at 501 nm, was assigned as the M-helix and similarly
15b was assigned as the P-helix.8,9,11,17 This work represents
the most diastereoselective complexation reported so far for the
synthesis of dinuclear bis(dipyrrinato) double helicates (dr )
31:69, de ) 38%).
The ethanoate-linked bis(dipyrrin) 12 gave only a single
isomer (16) upon coordination to Zn(II) (Figure 2), as deter-
mined by NMR spectroscopy and HPLC.9 Interestingly, the mass
spectrum for this complex indicated a mononuclear structure,
Zn[bis(dipyrrinato)], and so increasing the length of the linker
by two atom units (11 cf. 12) dramatically altered the outcome
of complexation in terms of both the nuclearity of the product
and the diastereoselectivity, thereby highlighting the reliance
of product outcome on ligand structure. Analysis using CD
showed that 16 and the Zn(II) complex prepared from the
enantiomeric ligand (14, incorporating (S)-binol) exhibited, as
expected for pseudoenantiomeric helicates, equal and opposite
molar ellipticities (Figure 4). By correlation,8,9,11,17 the complex
derived from (R)-binol was assigned as the M-helicate (later
confirmed by X-ray crystallography), and the complex derived
from (S)-binol was assigned as the P-helicate. The Co(II)
complex of 12 was also formed as a single diastereoisomeric
M-helicate according to mass spectrometry, HPLC, and CD.
These complexations are the most diastereoselective (>99.5%)
reported for the synthesis of dipyrrinato helicates. Furthermore,
the molar ellipticities of the pure mononuclear helicates are
remarkably high in the visible region with the molar ellipticities
for the binol unit being consistent in the UV range.
To further study the effect upon complexation of increasing
the linker length between the two dipyrrin units, the propanoate
derivative (13) was reacted with Zn(OAc)2 (Figure 2). As for
all the complexation reactions, the corresponding complexes
were obtained in excellent yield. Analysis of the reaction mixture
by chiral HPLC revealed two major isomers in a ratio of 33:
67. After separation, the first-eluted isomer (17a) was deter-
mined by mass spectrometry to be a mononuclear bis-
(dipyrrinato) complex. By correlation to the pure M-helical
Zn(II) complex 16 and previous reports,8,9,11,17 CD analysis
(Figure 5) confirmed that the monomer 17a adopted M-helicity.
Initially, the use of mass spectrometry (ESI+, EI+, and
MALDI) did not determine a molecular ion for 17b and instead
only the free-base of ligand 13 was detected. Presumably, the
ionization conditions caused decomplexation since CD, UV-
FIGURE 3. (A) HPLC trace with resolved 15a and 15b, CHIRALPAK
IA, CH3OH/CH3CN (60:40), 1 mL min-1, ambient temperature. (B)
Superimposed molar ellipticity of 15a and 15b, CH3OH/CHCl3 (98:
2): λ489nm 15a, ꢀ 440000 L mol-1 dm-1; [Θ]490nm 15a, 3.7 × 106 deg
cm2 dmol-1; λ490nm 15b, ꢀ 460000 L mol-1 dm-1; [Θ]497nm 15b, -3.8
× 106 deg cm2 dmol-1
.
Cognizant that coordination of unsymmetrical bis(dipyrrin)s
with tetrahedral metal ions gives helicates, and with the goal
of investigating the effects of the planar chiral binol moiety
upon the diastereoselectivity of complexation, ligands 11-13
were reacted with Zn(OAc)2 according to standard conditions
(Figure 2).14 HPLC and NMR spectroscopy were used to analyze
the crude reaction mixtures, and mass spectrometry enabled the
identification of monomeric and dimeric oligomers. Although
helicates bearing point-chiral appendages are formally diaste-
reoisomeric, separation of neither oligomers nor diastereoiso-
mers was possible by flash chromatography on silica or alumina.
However, as the gross helicity of the bis(dipyrrinato) complexes
renders the isomers pseudoenantiomeric, a chiral column
(CHIRALPAK IA) and HPLC proved to be most effective for
the resolution of the diastereoisomers and also allowed resolution
of monomeric and dimeric oligomers.
HPLC analysis of the crude reaction mixture from the Zn(II)
complexation of methanoate derivative 11 indicated the presence
of two dipyrrinato complex isomers (15a and 15b, as eluted)
in a ratio of 31:69 (Figure 3A). Separation of the resolved
isomers by preparative chiral HPLC and subsequent mass
spectrometry confirmed the formation of two diastereoisomeric
dinuclear complexes, Zn2[bis(dipyrrinato)]2. The separated di-
astereoisomers, both of which were fully characterized, were
found to exhibit approximately opposite ellipsoidal circular
dichrioism (CD) spectra (Figure 3B), as anticipated for pseu-
doenantiomeric helicates whereby the helical chirality stems
from the dipyrrinato units and not from the point-chiral
auxiliary.16 Diastereoisomer 15a, which exhibited a positive
(16) Barcena, H. S.; Holmes, A. E.; Zahn, S.; Canary, J. W. Org. Lett.
2003, 5, 709-711.
(17) Boiadjiev, S. E.; Lightner, D. A. Tetrahedron Asymm. 1999, 10,
2535-2550.
J. Org. Chem, Vol. 72, No. 13, 2007 4949

Ali et al.
of the complexation reaction mixture also led to an increase in
the formation of the mononuclear product (entries 2 and 3).
The results shown in Table 1 were used in the design of a
route to pure mononuclear helicate 17a. Indeed, when a dilute
solution of the purified dinuclear complex 17b was exposed to
an acidic solution (1 M HCl in methanol), HPLC analysis
confirmed that the free-base ligand was formed as a result of
decomplexation. The in-situ addition of triethylamine to the
solution containing free-base gave a complex which possessed
an identical retention time to the mononuclear complex observed
for the purified mononuclear complex 17a and which exhibited
a molecular ion (ESI+) corresponding to the mononuclear
complex. Furthermore, the recomplexed material exhibited CD
behavior identical to that of purified 17a. Thus, the dinuclear
complex was completely converted to the mononuclear complex
via such decomplexation/recomplexation under dilute conditions.
FIGURE 5. Molar ellipticity for purified complexes mononuclear 17a
and dinuclear 17b, CH3OH/CHCl3 (98:2): λ501nm 17a, ꢀ 93500 L mol-1
dm-1; [Θ]509nm, 1.3 × 106 deg cm2 dmol-1; λ503nm 17b, ꢀ 278400 L
The mononuclear Zn(II) bis(dipyrrinato) complex of 12 was
analyzed by X-ray crystallography. By layering a chloroform
solution of 16 with methanol (1:5), single crystals suitable for
X-ray diffraction studies were obtained. The preliminary
structure of 16 has been previously reported.9 At that time the
data collection on a series of crystals gave ambiguous results.
While all provided a subcell close to that reported here, many
crystals also satisfied either (or both of) a much larger cell with
many missing reflections and/or a cell where two angles were
clearly 90° but the third angle was close to 90° but significantly
different from it: these are classic symptoms for a twinned
crystal. The crystals themselves, generally thin plates, were very
fragile, and when manipulated in some directions they shattered
into a multitude of small crystals. However, the original crystals
were surprisingly plastic, simply bending when manipulated in
another direction. Furthermore, the bent crystals could be
straightened with apparently no loss to the external crystal form.
The systematic absences for the subcell with the data for the
preliminary structure suggested either space group P212121,
P21212, P2221, or (if monoclinic) P21. The absences for two of
the axial zones thus depended on a judgment call on whether
the 2n + 1 reflections were really all absent. Interestingly the
structure could be solved in all four space groups and refined
(with some restraints and the removal of a small number of
“miss-measured” reflections) to R factors in the low teens. In
all cases the molecular structure was clearly visible: ap-
proximately the same structure for each space group (two unique
molecules for P21), but the correct structure in the correct space
was not properly identified; we report here the resolution of
these problems.
mol-1 dm-1; [Θ]507nm 17b, -1.8 × 105 deg cm2 dmol-1
.
TABLE 1. Factors Affecting Mononuclear to Dinuclear (17a/17b)
Helicate Ratios
concentration Zn(II) concentration 13
entry
M
M
Zn(II)/L 17a/17b
1
2
3
0.09
0.01
0.01
0.01
9:1
1:1
1:1
1:2
3.2:1
4:1
8.0 × 10-4
8.0 × 10-4
vis spectroscopy, and NMR spectroscopy all indicated the
presence of bis(dipyrrinato) complex(es), rather than free-base.
The weak aryl-metal complexation between silver ions and
dipyrrins has previously been useful for chiral lanthanide shift
NMR analysis of bis(dipyrrinato) helicates.18 To enhance the
ionization and mass spectrometric detection of 17b, silver ions
in the form of silver trifluoroacetate were used to enhance
cationization19 (1:1 17b/AgCO2CF3 solution in methanol). The
ESI+ detection of the Ag+ adduct indicated 17b to be the
dinuclear Zn(II) complex of ligand 13, and this method of
cationization is proving to be a generally useful method for the
ESI+ analysis of dipyrrinato complexes in our laboratory.
Overall, complexation of 13 led to a mixture of mononuclear
and dinuclear complexes, 17a and 17b, in a 1:2 ratio, respec-
tively. The mononuclear isomer 17a was formed distereomeri-
cally pure, as determined by HPLC and NMR spectroscopy,
whereas dinuclear 17b was formed as a mixture of diastereoi-
somers that were not totally resolvable. The molar ellipticities
for 17a and 17b are shown in Figure 5. Remarkably, the
incorporation of a further two atom unit within the linker (12
cf. 13) results in a mixture of mononuclear and dinuclear
complexes of 13 versus a single mononuclear complex of 12,
and further highlights the acute reliance of oligomeric formation
on bis(dipyrrin) ligand structure.
The data were next collected on an imaging plate RAXIS
RAPID. The cylindrical geometry and wide aperture of this
system allowed the rotation geometry of the crystal to be
examined in detail. It then became clear that the larger cells,
previously detected, were not the result of twinning but rather
the consequence of slight displacements of portions of a single
crystal, with the displacements occurring preferentially in certain
zones. These data also suggested that the angles, previously
observed only to be close to 90°, could be the result of certain
reflections being elongated by slight displacements in the crystal
and thus the centers of some reflections were slightly displaced
from their true positions.
To enhance the formation of one oligomeric complex of 13
over the other, the reaction concentration and stoichiometry ratio
were varied in 1:1 MeOH/CHCl3, and HPLC analysis was used
to assess the product outcome (Table 1) as the mononuclear
and dinuclear isomers were well resolved. Decreasing the
stoichiometry of Zn(II)/13 from 9:1 to 1:1 led to a reversal in
the selectivity and predominance of the mononuclear product
17a (entries 1 and 2). Furthermore, decreasing the concentration
Further crystal samples of 16 were examined, this time taking
care to select only small, well-formed crystals that had no
previous history of manipulation. Several crystals had to be
selected until one was found that gave a clear cell, with little
(18) Thompson, A.; Dolphin, D. Org. Lett. 2000, 2, 1315-1318.
(19) Delcorte, A.; Bertrand, P. Anal. Chem. 2005, 77, 2107-2115.
4950 J. Org. Chem., Vol. 72, No. 13, 2007

Mono- and Dinuclear Bis(dipyrrinato) Complexes
FIGURE 6. ORTEP for 16 and corresponding packing diagram for the unit cell (50% probability ellipsoids).
evidence of displacements having occurred. The structure from
this crystal solved quickly and tidily in space group P212121
and refined to R ) 4.6% without restraints or any other
manipulation of the reflection data. The structure, solved in P21
and then examined by PLATON,20 reported 98% in P212121.
The absolute configuration of 16 was clearly determined as the
M-helix with a Flack parameter of 0.012(3), consistent with the
configuration assigned using CD data and conformational
analysis.9
An examination of the completed structure (Figure 6) reveals
the source of the difficulties that had been originally encoun-
tered. A packing diagram of the unit cell shows that the
molecules are arranged in such a way that, although there are
interactions between molecules in a layer, there is a wide gap
between the layers where there is nothing but H‚‚‚H contacts
to hold the layers in place. This is the classic requirement for
crystals that bend,21 and equally the condition that can cause
portions of a crystal to displace on being cut or stressed with
the point of a needle; whether the crystal undergoes bending or
displacement depends upon the direction of the stress placed
upon it. With this knowledge, complexes of bis(dipyrrin)s will
be handled with extreme care during future X-ray crystal-
lographic analyses thus minimizing bending and displacement
(slipping of layers).
complexation, and the oligomeric selectivity can be tuned by
variation of concentration and stoichiometry. Both CD and
HPLC were critical to the analysis of all of the asymmetric
complexation reactions, and these techniques are applicable to
the analysis of dipyrrinato complexes by virtue of the strong
chromophoric units within the neutral complexes. Extensive
X-ray crystallographic investigations confirmed the helicity of
the mononuclear Zn(II) helicates and provided insight into
methods that should be used to minimize bending and displace-
ment within crystals of bis(dipyrrin) complexes.
Experimental
Di[benzyl-4,4′-[(R)-binolmethanoate-3,5-dimethyl]-1H-pyrrole-
2-carboxylate] (7). According to a modification of a reported
procedure,15 to a suspension of carboxylic acid 415 (819 mg, 3.0
mmol) in dry toluene (25 mL) under nitrogen was added trifluo-
roacetic anhydride (765 mg, 3.6 mmol). The resultant mixture was
stirred at room temperature until dissolution of the suspended solute
occurred. (R)-Binol (430 mg, 1.5 mmol) was added as a solid, and
the solution was stirred for 24 h before being diluted with ethyl
acetate (25 mL). The mixture was washed with 2 M NaOH (2 ×
25 mL) and brine (2 × 25 mL). The organic fraction was dried
over Na2SO4 and then concentrated in vacuo. The resultant crude
product was purified by flash column chromatography eluting with
30% ethyl acetate in hexane to give, upon concentration, the title
product as a white powder (1.06 g, 89%); mp 107-109 °C. UV-
vis λmax/nm, 276 (ꢀ 64400); [Θ]235, -1.89 × 105; δH (500 MHz;
CDCl3) 9.12 (2H, br s), 7.92 (2H, d, J 9.0), 7.86 (2H, d, J 8.0),
7.51 (2H, d, J 9.0), 7.39 (2H, t, J 8.0), 7.22-7.33 (14H, m), 5.19
(4H, s), 2.16 (6H, s), 1.83 (6H, s); δC (125 MHz; CDCl3) 162.9,
161.3, 147.0, 140.4, 136.1, 133.9, 132.5, 131.4, 129.0, 128.7, 128.3,
128.1, 128.0, 126.7, 126.2, 125.6, 124.1, 122.7, 117.6, 112.5, 66.0,
13.8, 11.6; m/z (ESI+) 819.2 (M + Na)+.
Conclusions
The most diastereoselective syntheses of helical mononuclear
Zn(II) bis(dipyrrinato) complexes are reported, using ligands
templated by the incorporation of binol within the linker.
Increasing the overall length of the linker leads to mononuclear
Zn(II) bis(dipyrrinato) helicates with excellent (>99%) diaste-
reoselectivity and the sense of helicity is assigned using circular
dichroism and confirmed by X-ray crystallography. Further
increase of the length of the linker results in mixtures of
mononuclear and dinuclear helicates formed by asymmetric
3,3′-[(R)-Binolmethanoate]-bis[2,4,dimethyl-5-[(4-ethyl-3,5-
dimethyl-1H-pyrrol-2-ylidene)methyl]]-, 1H Pyrrole Dihydro-
bromide (11). To dipyrrole 7 (319 mg, 0.4 mmol) and 10% Pd on
activated carbon (20 mg) under nitrogen was added THF (20 mL).
The reaction mixture was exposed to hydrogen at 1 atm and stirred
continuously for 15 h. The reaction mixture was filtered through
Celite which was then washed with THF (5 mL) and MeOH (5
mL). Removal of the solvents in vacuo from the combined organic
(20) Spek, A. L. J. Appl. Cryst. 2003, 36, 7-13.
(21) Reddy, C. M.; Kirchner, M. T.; Gundakaram, R. C.; Padmanabhan,
K. A.; Desiraju, G. R. Chem.sEur. J. 2006, 12, 2222-2234.
J. Org. Chem, Vol. 72, No. 13, 2007 4951

Ali et al.
fractions gave the dicarboxylic acid which was immediately
decarboxylated by stirring for 1 h in trifluoroacetic acid (20 mL)
at room temperature. To the resultant solution, was added CH2Cl2
(25 mL), and the solution was then washed with saturated Na2CO3
(2 × 25 mL), added slowly in portions, followed by washing with
brine (2 × 25 mL). The organic fraction was dried over Na2SO4,
and removal of the organic solvent in vacuo gave the R-free
dipyrrole. Without further purification, the R-free dipyrrole was
dissolved in THF (30 mL) and 4-ethyl-2-formyl-3,5-dimethylpyrrole
(10) (121 mg, 0.80 mmol), and three drops of concentrated HBr
(48%) were added to the mixture. The reaction mixture was stirred
at 40 °C for 1.5 h. Removal of the solvent in vacuo, followed by
dissolution of the residue in CH2Cl2 (40 mL), drying over MgSO4,
and removal of the solvent in vacuo gave the crude product.
Trituration of the crude solid with diethyl ether gave the title
compound as a red/brown powder (358 mg, 94%); mp (dec) >
172 °C. UV-vis λmax/nm, 497 (ꢀ 125100); [Θ]484, -7.79 × 105;
δH (500 MHz; CDCl3) 13.49 (2H, br s), 12.94 (2H, br s), 8.04 (2H,
d, J 9.0), 7.98 (2H, d, J 8.0), 7.50-7.55 (4H, m), 7.34-7.36 (4H,
m), 7.08 (2H, s), 2.73 (6H, s), 2.45 (4H, q, J 7.5), 2.35 (6H, s),
2.29 (6H, s), 2.13 (6H, s), 1.12 (6H, t, J 7.5); δC (125 MHz; CDCl3)
161.7, 160.8, 155.5, 146.5, 146.3, 144.5, 133.6, 133.1, 131.5, 129.4,
128.5, 128.2, 127.0, 126.1, 125.9, 124.5, 123.8, 122.2, 120.1, 116.3,
17.2, 14.3, 14.1, 13.3, 11.6, 10.1; m/z (ESI+) 795.2 (MH - 2HBr)+.
Zinc Bis[3,3′-[(R)-binolmethanoate]-bis[2,4,dimethyl-5-[(4-
ethyl-3,5-dimethyl-1H-pyrrol-2-ylidene)methyl]-1H-pyrrolato]
(15). To a solution of bis(dipyrrin) hydrobromide salt 11 (382 mg,
0.40 mmol) in CHCl3 (15 mL) was added a solution of Zn(OAc)2‚
2H2O (812 mg, 3.7 mmol) and NaOAc‚3H2O (504 mg, 3.7 mmol)
in CH3OH (15 mL). The reaction mixture was stirred at 40 °C for
2.5 h. Removal of solvent in vacuo, was followed by dissolution
of the residue in CH2Cl2 (20 mL), washing with H2O (2 × 10 mL),
and drying the organic fraction over MgSO4. Removal of the solvent
in vacuo gave the crude product as a film. Trituration of the crude
film with hexane gave the title compound as a red/brown powder
in a mixture of two diastereoisomeric dinuclear complexes 15a and
15b in a 31:69 ratio, respectively, according to chiral HPLC (332
mg, 87%). 15a: mp (dec) > 255 °C; UV-vis λmax/nm, 489 (ꢀ
438800); [Θ]490, 3.65 × 106; δH (500 MHz, CDCl3) 7.77 (4H, d, J
8.5), 7.45 (2H, d, J 8.5), 7.33-7.35 (4H, m), 7.19-7.21 (2H, m),
7.00 (2H, s), 2.40 (6H, s) 2.30 (4H, q, J 7.5), 2.25 (6H, s), 1.69
(6H, s), 1.42 (6H, s), 1.01 (6H, t, J 7.5); δC (126 MHz, CDCl3)
164.3, 163.6, 156.3, 147.7, 140.5, 139.1, 134.3, 134.0, 133.6, 131.3,
129.0, 127.8, 126.5, 125.3, 122.8, 121.5, 115.3, 18.0, 16.7, 15.0,
14.8, 11.8, 10.2; m/z (ESI+) 1741.4 (M+Na)+. 15b: mp (dec) >
271 °C; UV-vis λmax/nm, 490 (ꢀ 463500); [Θ]497, -3.84 × 106;
δH (500 MHz, CDCl3) 7.98 (2H, d, J 9.0), 7.94 (2H, d, J 8.0), 7.65
(2H, d, J 9.0), 7.43-7.46 (4H, m), 7.28 (2H, d, J 3.5), 6.82 (2H,
s), 2.27 (4H, q, J 7.5), 2.09 (6H, s), 2.08 (6H, s), 1.73 (6H, s), 1.41
(6H, s), 0.94 (6H, t, J 8.0); δC (126 MHz, CDCl3) 163.6, 163.3,
158.5, 147.7, 141.7, 140.3, 139.0, 134.2, 134.0, 133.0, 131.4, 128.8,
128.1, 126.5, 126.4, 125.3, 124.2, 123.4, 122.4, 115.3, 18.0, 16.9,
14.9, 14.8, 11.0, 9.9; m/z (ESI+) 1739.3 (M+Na)+.
Zinc Bis[3,3′-(R)-binolpropanoate]-bis[2,4,dimethyl-5-[(4-
ethyl-3,5-dimethyl-1H-pyrrol-2-ylidene)methyl]-1H-pyrrolato]
(17). Following the general procedure as for the preparation of 15,
to a solution of bis(dipyrrin) 13 (319 mg, 0.30 mmol) in CHCl3
(15 mL) was added a solution of Zn(OAc)2‚2H2O (615 mg, 2.80
mmol) and NaOAc‚3H2O (381 mg, 2.80 mmol) in CH3OH (15 mL).
Workup as before gave the title compound as a red/brown powder
(262 mg, 86%) in a 33:67 mixture of mononuclear and dinuclear
complexes 17a and 17b, respectively, according to chiral HPLC.
17a: UV-vis λmax/nm, 501 (ꢀ 93500); [Θ]509, 1.32 × 106; δH (500
MHz, CDCl3) 7.89 (4H, d, J 8.5), 7.42 (2H, t, J 8.0), 7.20-7.29
(4H, m), 7.08 (2H, d, J 9.0), 7.01 (2H, s), 2.66-2.76 (4H, m),
2.35 (4H, q, J 7.5), 2.25 (6H, s), 2.24 (6H, s), 2.13-2.18 (4H, m),
1.93 (6H, s), 1.53 (6H, s), 1.02 (6H, t, J 7.5); δC (125 MHz, CDCl3)
171.4, 156.8, 156.0, 146.9, 137.1, 137.0, 135.8, 135.2, 133.2, 131.3,
129.8, 129.3, 127.9, 126.6, 126.0, 125.6, 124.3, 123.3, 121.9, 120.8
33.4, 20.5, 18.0, 15.0, 14.9, 14.8, 10.0, 9.9; m/z (ESI+) 914.3
(M+2H)+. 17b: UV-vis λmax/nm, 503 (ꢀ 278400); [Θ]507, -1.8
× 105; m/z (ESI+ using AgCO2CF3) 1937.6 (M+Ag+6H)+.
Acknowledgment. Support for this research was provided
by the Natural Sciences and Engineering Research Council
(NSERC) of Canada, Dalhousie University, the Canada Founda-
tion for Innovation and the Nova Scotia Research and Innovation
Trust. We thank Mr. K. S. Cameron for early synthetic work
relating to the preparation of 12 and 13, and Mr. X. Feng and
Dr. J. S. Grossert for work and discussions regarding mass
spectrometry.
Supporting Information Available: Synthetic procedures and
characterization data for new compounds. CCDC 622546 contains
the supplementary crystallographic data for this paper. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO070569J
4952 J. Org. Chem., Vol. 72, No. 13, 2007