A diastereoselective process induced in a curved aromatic molecule: oxidation of thioether-substituted subphthalocyanines

Article abstract of DOI:10.1016/j.tetlet.2008.11.126

Different sulfoxide-substituted subphthalocyanines have been synthesized by oxidation reaction of the corresponding thioether precursors. We have observed for the first time that when the oxidation takes place close to the macrocyclic core, the intrinsically chiral subphthalocyanine can induce a high degree of diastereoselectivity in this process.

Full text of DOI:10.1016/j.tetlet.2008.11.126

Tetrahedron Letters 50 (2009) 860–862
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Tetrahedron Letters
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A diastereoselective process induced in a curved aromatic molecule:
oxidation of thioether-substituted subphthalocyanines
*
David González-Rodríguez, Tomás Torres
Universidad Autónoma de Madrid, Departamento de Química Orgánica (C-I), Facultad de Ciencias, Cantoblanco, 28049-Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Different sulfoxide-substituted subphthalocyanines have been synthesized by oxidation reaction of the
corresponding thioether precursors. We have observed for the first time that when the oxidation takes
place close to the macrocyclic core, the intrinsically chiral subphthalocyanine can induce a high degree
of diastereoselectivity in this process.
Received 29 October 2008
Accepted 24 November 2008
Available online 7 December 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Subphthalocyanines (SubPcs, Fig. 1a)1 are 14
p
-electron aro-
interesting chirooptical and liquid-crystalline properties, or to
use them as sensors for chiral substrates.
matic boron macrocycles that mainly differ from their higher
homologues, the phthalocyanines (Pcs),2 in that they present three
isoindole units arranged in a cone-shaped structure. These singular
three-dimensional chromophores are continuously finding poten-
tial uses in applied fields, such as nonlinear optics,3 energy and
electron transfer systems,4 light-emitting diodes,5 anion sensing,6
and supramolecular chemistry.7
As part of an ongoing research project aimed at obtaining high
amounts of enantiomerically pure SubPc products via diastereo-
meric resolution, we have studied the functionalization of these
macrocycles with chiral sulfoxide groups, widely employed in
asymmetric synthesis,13 at the peripheral positions of the macro-
cycle. To date, the incorporation of sulfoxide functionalities on
the SubPc macrocycle has not been reported. A probable reason
is that, quite often, the main problem encountered in the function-
alization of these singular molecules is their chemical instability,
which usually leads to decomposition via ring-opening. In addi-
tion, the harsh conditions required for their synthesis limit to a
great extent the kind of functional groups that can be introduced
in the precursor phthalonitriles.
SubPcs are generated by cyclotrimerization reaction of phthalo-
nitriles in the presence of a boron halide.8 When the precursor
phthalonitrile does not have
a C2v symmetry, a mixture of
C3- and C1-symmetric regioisomers is formed.9 Due to their curved,
rigid structure, each of these SubPc regioisomers is actually consti-
tuted by a racemic mixture of enantiomers, which have been
described by means of the helical descriptors M and P, regarding
the SubPc macrocycle as a superimposition of three chiral helices
going along the key X–B–N–C dihedral angles (Fig. 1b).
And in fact, our initial attempts to directly introduce sulfoxide
groups into the SubPc skeleton by condensation of 4-(p-tolylsulfi-
nyl)-phthalonitrile in the presence of BCl3 were, as expected,
unsuccessful. The reaction yielded, in contrast, the corresponding
Despite the great interest in intrinsically chiral,
p-conjugated
molecules in the areas of materials science and supramolecular
chemistry,10 the resolution and application of SubPcs in a pure chi-
ral form have not been developed to a great extent so far. SubPc
enantiomers have been separated in an analytical scale by chiral
HPLC11 and their circular dichroic response, having a mirror sym-
metry with respect to the baseline, has been recorded.12 In addi-
tion, chiral self-discrimination effects in racemic mixtures have
been recently observed. Concretely, in the presence of a palladium
complex, a tripyridyl-substituted SubPc enantiomer only recog-
nizes its opposite upon the formation of supramolecular M3L2
cages under thermodynamic control.7b There is still a lot of excite-
ment, however, in exploiting other aspects of SubPc chirality. For
instance, it would be very interesting to organize chiral SubPcs in
helical columns of a preferred handedness, which may show very
* Corresponding author. Tel.: +34 91 497 4151; fax: +34 91 497 3966.
E-mail address: tomas.torres@uam.es (T. Torres).
Figure 1. (a) Top and side view of the SubPc molecular structure. (b) SubPc regio-
and stereoisomers formed in the condensation of a 4-substituted phthalonitrile.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.11.126

D. González-Rodríguez, T. Torres / Tetrahedron Letters 50 (2009) 860–862
861
CN
CN
CN
CN
CN
CN
CN
CN
NC
NC
CN
CN
NC
NC
+
+
O
S
S
S
S
S
BCl3
BCl3
p-xylene
p-xylene
reflux
reflux
BCl3
p-xylene
reflux
BCl3
p-xylene
reflux
S
S
S
N
N
N
N
N
B
N
B
Cl
N
Cl
N
N
N
S
N
N
N
N
N
N
N
B
N
B
Cl
Cl
5
4
S
N
N
N
N
MCPBA (1.1 eqs.)
CH2Cl2, -78ºC
MCPBA (1.1 eqs.)
CH2Cl2, -78ºC
S
N
N
S
S
1
2
O
S
MCPBA (6.6 eqs.)
CH2Cl2, -78ºC
S
O
N
N
N
B
Cl
N
N
N
B
Cl
O
O
N
N
S
N
N
N
N
6a + 6b
7a + 7b
BCl3
N
N
N
B
NC
NC
p-xylene
Cl
Scheme 2. Synthesis of SubPcs 6 and 7 as a mixture of diastereoisomers (a and b).
N
N
reflux
S
O
S
O
O
in which the main component is the unsubstituted SubPc, followed
by compound 4 or 5. As a result, chromatographic separation of the
mixture is greatly facilitated at the expense of a higher loading of
phthalonitrile.15
O
N
O
S
O
3
The oxidation reaction of 4 and 5 in the presence of 1.1 equiv of
MCPBA led now to sulfoxide-SubPcs 6 and 7, respectively, in good
yields (ꢀ80%). A small amount of the corresponding sulfone-Sub-
Pcs was as well obtained. All compounds were purified and charac-
terized by NMR, LSI-MS, HR-MS, UV–vis, and IR techniques.
Figure 2 shows the aromatic region of the 1H NMR spectrum of
compounds 4 and 6. The formation of a new chiral center in the
molecule led to a 1:1 mixture of SubPc diastereoisomers (6a and
Scheme 1. Synthesis of SubPcs 1, 2, and 3.
trithioether-substituted SubPc (1, Scheme 1), the boron halide
playing the role of condensation template and reducing agent at
once.
Since alkyl- and aryl-thioether SubPcs can be easily obtained by
direct condensation of the respective phthalonitriles, we then
looked for efficient methods to carry out the oxidation of the sulfur
atoms that preserved the structure of the macrocycle. We found
that the use of m-chloroperbenzoic acid (MCPBA) in CH2Cl2 at
low temperatures was a good option. Oxidation was fast and virtu-
ally quantitative, while SubPc decomposition was not significant
providing the temperature was kept at À78 °C.
φ
χ
X
β
γ
α
N
N
N
B
Cl
N
δ
N
ε
N
χ
ε
SubPcs 1 and 2 were thus synthesized from 4-(p-tolylthio)pht-
halonitrile or 3-(p-tolylthio)phthalonitrile, respectively.14 The oxi-
dation of compound 1, having three thioether groups, in the
presence of 3 equiv of MCPBA was, however, quite difficult to stop
at the level of the trisulfoxide product. The reaction instead led to a
complex mixture of unsymmetrical SubPcs substituted with thioe-
ther, sulfoxide, and sulfone groups. On the other hand, complete
oxidation in the presence of an excess of MCPBA led to compound
3 in 59% yield (Scheme 1). This product can also be accessed by di-
rect condensation of 4-(p-tolylsulfonyl)-phthalonitrile in the pres-
ence of BCl3.3b
φ
4
δ
γ
α
β
ε
δ
χ
6
φ
α
γ
β
Therefore, the oxidation of unsymmetrically substituted SubPcs
4 and 5, equipped with a single thioether unit at the b- or a-posi-
tions of the macrocycle, respectively, was next examined (Scheme
2). These products were obtained by the mixed condensation reac-
tion of 4-(p-tolylthio)-phthalonitrile (for 4) or 3-(p-tolylthio)-pht-
halonitrile (for 5) and phthalonitrile in the presence of BCl3. The
use of a high excess (9 equiv) of phthalonitrile generated a mixture
9.00
8.50
8.00
7.50
(ppm)
Figure 2. Aromatic region of the 1H NMR spectra in CDCl3 of SubPcs 4 and the 1:1
mixture of diastereoisomers of SubPc 6 (6a and 6b).

862
D. González-Rodríguez, T. Torres / Tetrahedron Letters 50 (2009) 860–862
6b), manifested by a clear splitting of some of the aromatic proton
signals. This is specially evident in the protons that are in ortho-po-
of specific interactions between the MCPBA reagent and one of the
sides of the SubPc ring in the transition state.
sition to the sulfoxide group (
a
, b, and
v
in Fig. 2). Such a splitting
This is one of the few cases of diastereoselective reactions in-
duced by a curved aromatic substrate,16 and certainly the first
one in SubPc chemistry. The preliminary results obtained from
these experiments are encouraging for the utilization of asymmet-
ric oxidation procedures13 on peripherally or axially thioether-
substituted SubPcs. The separation of SubPc diastereoisomers
bearing an enantiomerically pure sulfoxide group would lead, after
elimination of the stereogenic center, to the desired enantiomeric
macrocycles. These optically active chromophores may show very
valuable properties to be applied in supramolecular chemistry and
molecular materials science.
in SubPc diastereoisomers has also been observed in SubPc-fullero-
pyrrolidine dyads.4a Although we could separate these two diaste-
reoisomers by HPLC in an analytical scale, any attempt to isolate
them by column chromatography in higher amounts was fruitless.
On the other hand, when we carried out the oxidation reaction
of compound 5, bearing the sulfoxide group at the SubPc
tion, we observed a totally different behavior. In contrast to com-
pound 4, the reaction of led to 95:5 mixture of
a posi-
5
a
diastereoisomers, as determined by 1H NMR and HPLC analysis.
Moreover, in this case, the two diastereoisomers could be sepa-
rated by standard column chromatography, yielding compounds
7a and 7b in 76% and 4% yields, respectively. Figure 3 shows the
aromatic region of the 1H NMR spectra of the mixture of sulfox-
ide-SubPcs formed in the oxidation reaction of 5, as well as of
the isolated diastereomeric products 7a and 7b.
The proximity of the thioether group to the core of the chiral
macrocycle in 5, when compared to SubPc 4, is likely to be respon-
sible for the diastereoselectivity observed in this oxidation process.
Molecular models, however, did not help in establishing a prefer-
ential attack mode of the oxidizing agent that could account for
such selectivity. It may be that at such low temperatures, the phe-
nylsulfide moiety in 5 adopts a well-defined conformation that is
then subject to attack from only one of the sides of the macrocycle.
Another possible explanation for this effect would be the existence
Acknowledgments
Funding from MEC (CTQ2008-00418/BQU, CONSOLIDER-INGE-
NIO 2010 CDS2007-00010 NANOCIENCIA MOLECULAR, and ESF-MEC
MAT2006-28180-E, SOHYDS), COST Action D35, and Comunidad
de Madrid (S-0505/PPQ/000225) is acknowledged.
Supplementary data
Supplementary data (synthetic procedures and characterization
data of compounds C3-1, C1-1, C3-2, C1-2, 3, 4, 5, 6, 7a, and 7b) asso-
ciated with this paper can be found, in the online version, at
doi:10.1016/j.tetlet.2008.11.126.
References and notes
φ
β
α
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835–853; (b) Torres, T. Angew. Chem., Int. Ed. 2006, 45, 2834–2837.
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Brasselet, S.; Ledoux, I.; Zyss, J. J. Am. Chem. Soc. 1996, 118, 2746–2747; (b) del
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χ
γ
X
N
N
N
B
Cl
δ
N
N
ε
N
CHCl3
ε
χ + β
5
φ
δ
α
γ
4. SubPcs have been employed as electron donors: (a) González-Rodríguez, D.;
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Eur. J. 2005, 11, 3881–3893; or as electron acceptors: (c) González-Rodríguez,
D.; Torres, T.; Olmstead, M. M.; Rivera, J.; Herranz, M. A.; Echegoyen, L.;
Atienza-Castellanos, C.; Guldi, D. M. J. Am. Chem. Soc. 2006, 128, 10680–10681.
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ε
(7a) + ε(7b)
CHCl3
ε
(7a) + ε(7b) + γ(7a)
α(7a)
7a + 7b
χ(7a)
β(7a)
φ(7a)
χ(7b)
β(7b)
γ(7b)
φ(7b)
α(7b)
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E.; Martínez-Díaz, M. V.; Torres, T.; Coronado, E. Adv. Funct. Mater. 2006, 16,
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CHCl3
7a
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K.; Persoons, A. Chem. Commun. 1999, 17, 1661–1662; (b) Claessens, C. G.;
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ε
χ
δ
φ
β
γ
α
7b
χ
ε
CHCl3
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Claessens, C. G.; Torres, T. Eur. J. Org. Chem. 2000, 1603–1607.
δ
φ
β
γ
α
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14. The C3 and C1 regioisomers of 1 and 2 (C3-1, C1-1, C3-2 and C1-2), could be
isolated and were characterized independently (see the Supplementary data).
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Phthalocyanines., in press.
9.00
8.50
8.00
7.50
7.00
(ppm)
Figure 3. Aromatic region of the 1H NMR spectra in CDCl3 of SubPcs 5, the 95:5
mixture of diastereoisomers of SubPc 7 (7a + 7b) as isolated from the reaction
mixture, and compounds 7a and 7b after separation by column chromatography.
16. More is known, however, on stereoselecitve processes in helicene chemistry:
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