Photolabile calixarene-based rosette

Article abstract of DOI:10.1139/v03-057

A model calix[4]arene-based rosette carrying two alternating photocleavable dithianyl-hydroxy-methyl moieties and two benzophenonecarboxylates was synthesized and shown to be capable of photoinduced fragmentation, with efficiency comparable to that of the

Full text of DOI:10.1139/v03-057

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Photolabile calixare ne -bas e d ros e tte
Za iguo Li, Huy Chiu, a nd Andre i G. Kuta te la dze
Abstract: A model calix[4]arene-based rosette carrying two alternating photocleavable dithianyl-hydroxy-methyl moi-
eties and two benzophenonecarboxylates was synthesized and shown to be capable of photoinduced fragmentation, with
efficiency comparable to that of the externally sensitized parent dithiane–benzaldehyde adducts.
Key words: photoinduced electron transfer, photofragmentation, calixarene, dithiane–carbonyl adducts.
Résumé : On a effectué la synthèse d’une rosette modèle à base de calix[4]arène portant deux portions alternées de di-
thianyl-hydroxy-méthyle photoclivables et de deux benzophénonecarboxylates; on a démontré qu’il est possible d’en
provoquer une fragmentation photoinduite avec une efficacité comparable à celle des adduits parents dithiane–benzaldé-
hyde sensibilités d’une façon externe.
Mots clés : transfert d’électron photoinduit, photofragmentation, calixarène, adduits dithiane–carbonyle.
[
Traduit par la Rédaction] Li et al. 810
Introduc tion
Calixarenes modified at their upper or lower rim are often
used as scaffolds for modular assembly of complex macro-
molecules. The relative rigidity of the calixarenic macro-
cycle makes it a spacer of choice for positioning various
substituents and (or) molecular blocks in a daisy-wheel-like
fashion. Specific examples range from ion-selective chela-
tors and ionophores (1) to tethered polypeptides capable of
protein surface recognition (2) to recognition-based sensing
of other peptides (3), etc. We suggest that an attractive func-
tional feature for such modular designs would be to assem-
ble them by interconnecting the core scaffold and the
auxiliary peripheral modules via photolabile tethers. This in
essence is the approach that we have been developing based
on the recently discovered photofragmentation reaction of
α-hydroxyalkyl dithianes and related compounds in the pres-
ence of an electron transfer sensitizer, such as benzophenone
Mechanistic aspects of similar fragmentations in cation–
radicals containing other heteroatoms were studied by
Arnold, Whitten, Maslak, and co-workers (6).
We use such dithiane–carbonyl adducts as photolabile
latches” that can hold together various molecular blocks,
“
and are capable of releasing them upon photoirradiation (7).
(
4). These compounds are readily available through nearly
quantitative lithiodithiane additions to carbonyl compounds
a reaction that was developed three decades ago by Corey
—
and Seebach (5), and that over the years has been imple-
mented in numerous successful synthetic procedures.
In this communication, we report the synthesis of a model
calixarene-based photocleavable rosette outfitted with an in-
ternal sensitizer, and its photoinduced fragmentation.
Unsubstituted dithiane is used as a simple “model” of a
macromolecular block that potentially can be attached to the
calixarenic scaffold via dithianes substituted at position 5,
for example 5-carboxy- or 5-hydroxymethyldithiane.
The photofragmentation is initiated by photoinduced elec-
tron transfer from the dithiane moiety to the excited triplet
benzophenone, followed by mesolytic cleavage in the gener-
ated cation–radical (4).
Received 10 January 2003. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 30 June 2003.
This paper is dedicated to Professor Don Arnold.
1
Z. Li, H. Chiu, and A.G. Kutateladze. Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208-
2
436, U.S.A.
1Corresponding author (e-mail: akutatel@du.edu).
Can. J. Chem. 81: 807–810 (2003)
doi: 10.1139/V03-057
© 2003 NRC Canada

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Can. J. Chem. Vol. 81, 2003
Scheme 1. (a) CHCl OCH –SnCl –CHCl , 46%; (b) NaBH –EtOH 86%; (c) CHCl OCH –TiCl –CHCl , 41%; (d) excess lithiated
2
3
4
3
4
2
3
4
3
dithiane, THF, –78°C to r.t., 42%; (e) PhC(O)PhCOCl, Et N, CH Cl , 20 h (see text).
3
2
2
The overall synthetic scheme is presented below
Scheme 1). Commercially available calix[4]arene was
tetraalkylated with 2-ethoxyethylbromide to give 1 and then
bis-formylated according to the procedure by Arduini et al.
8) yielding 2. The dialdehyde 2 was reduced with sodium
1–4, are represented by two sets of doublets each in the
compound 5 (and 7).
2
(
An alternative rationale for the observed doubling of the
benzylic peaks is that 5 is a single diastereomer, but the
crowded steric environment in it prevents free rotation of the
dithianyl groups and they are caught in an unsymmetrical
conformation, resulting in magnetically nonequivalent pro-
tons. Formation of only one diastereomer is, however, un-
likely. We heated the sample of 5 in deuterated chloroform
to 55°C and did not observe any coalescence of the benzylic
signals in NMR. We, therefore, interpret the observed NMR
(
borohydride and the formylation was repeated. The C -sym-
2
metric dialdehyde–diol 4 was reacted with excess lithiated
dithiane to furnish bis-adduct 5 (42%).
Addition of dithianyl anion to dialdehyde 4 was expected
to produce a pair of diastereomers. Given the large spatial
separation of the chiral centers, we did not expect any
diastereoselectivity and the NMR spectrum of bis-adduct 5
seems to corroborate this conclusion. As is shown in Fig. 1,
the proton signal for the primary benzylic alcohols, which is
a singlet in 4, is represented by two separate peaks in 5 (4.17
spectrum as
a 1:1 mixture of diastereomers. Both
diastereomers are suitable for the assembly of the target
photolabile rosettes. In this study we employed benzophe-
none-4-carboxylic acid as a tethered internal sensitizer. It
was first converted into p-benzoylbenzoyl chloride via reac-
tion with oxalyl chloride in dichloromethane and then cou-
and 4.15 ppm). Also, the calixarenic methylenes, Ar-CH -Ar
2
(
both sets of four “in” and four “out”), which are doublets in
2
1
5
6
6
,17-Dihydroxymethyl-25, 26, 27, 28-tetrakis(2-ethoxyethoxy)calix[4]arene (3): H NMR data (400MHz, CDCl ): 6.89 (d, J = 8.0 Hz, 4H),
3
.76 (t, J = 8.0 Hz, 2H), 6.40 (s, 4H), 4.51 (d, J = 13.2 Hz, 4H), 4.24 (t, J = 6.4 Hz, 4H), 4.16 (s, 4H), 4.00 (t, J = 5.6 Hz, 4H), 3.89 (t, J =
.4 Hz, 4H), 3.81 (t, J = 5.6 Hz, 4H), 3.59–3.49 (m, 8H), 3.14 (d, J = 13.6 Hz, 4H), 1.98 (s, 2H), 1.24–1.16 (m, 12H). 5,17-Diformyl-11,23-
dihydroxymethyl-25,26,27,28-tetrakis(2-ethoxyethoxy)calix[4]arene (4): 9.66 (s, 2H), 7.24 (s, 4H), 6.61 (s, 4H), 4.57 (d, J = 13.6 Hz, 4H),
.27 (t, J = 6.4 Hz, 4H), 4.24 (s, 4H), 4.09 (t, J = 6.4 Hz, 4H), 3.83–3.77 (m, 8H), 3.56–3.46 (m, 8H), 3.24 (d, J = 13.6 Hz, 4H), 1.22–1.14
4
(m, 12H). Bis-adduct 5: 7.23 (s, 2H), 7.15 (s, 2H), 6.66–6.62 (m, 4H), 4.84 (d, J = 7.3 Hz, 2H), 4.54 and 4.51 (2d, J = 12.4 Hz, 4H), 4.36
(t, J = 6.8 Hz, 4H), 4.16 (d, J = 7.3 Hz, 2H), 4.06 (t, J = 6.6 Hz, 4H), 3.97–3.92 (m, 4H), 3.77–3.72 (m, 4H), 3.61–3.50 (m, 8H), 3.31–3.27
(m, 4H), 3.21 and 3.17 (2d, J = 12.4 Hz, 4H), 3.00–2.71 (m, 8H), 2.13–1.90 (m, 4H), 1.22 (m, 12H). Monobenzoylated compound 6: 8.21
(d, J = 8.1 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 8.8 Hz, 2H), 7.65 (t, J = 7.3 Hz, 1H), 7.52 (t, J = 7.3 Hz, 2H), 7.35 (d, J =
2
4
4
8
6
4
6
2
.2 Hz, 1H), 7.29 (d, J = 2.2 Hz, 1H), 7.20 (d, J = 2.2 Hz, 1H), 7.06 (d, J = 2.2 Hz, 1H), 6.39–6.28 (m, 4H), 6.18 (d, J = 8.1 Hz, 1H),
.76–4.70 (m, 2H), 4.50–4.43 (m, 4H), 4.36 (d, J = 7.3 Hz, 1H), 4.27–4.20 (m, 4H), 3.92–3.70 (m, 16H), 3.56–3.46 (m, 8H), 3.18–3.09 (m,
H), 3.01–2.77 (m, 8H), 1.82–1.72 (m, 2H), 1.18–1.04 (m, 12H). Bis-benzoylated compound 7: 8.24 (d, J = 8.8 Hz, 4H), 7.87 (d, J =
.8 Hz, 4H), 7.8 (d, J = 8.8 Hz, 4H), 7.67 (t, J = 7.3 Hz, 2H), 7.54 (t, J = 7.3 Hz, 4H), 7.38 (d, J = 2.2 Hz, 2H), 7.32 (d, J = 2.2 Hz, 2H),
.37 (d, J = 2.2 Hz, 2H), 6.27 (d, J = 2.2 Hz, 2H), 6.21 (d, J = 8.1 Hz, 2H), 4.74 (d, J = 8.1 Hz, 2H), 4.48 and 4.44 (2d, J = 13.2 Hz, 4H),
.27 (m, 4H), 3.89–3.70 (m, 16H), 3.53 (m, 8H), 3.18 (d, J = 13.2 Hz, 4H), 3.05–2.81 (m, 8H), 1.80–1.75 (m, 2H), 1.18 (t, J = 7.3 Hz,
1
+
H), 1.10 (t, J = 7.3 Hz, 6H). MS (m/z): 1485.5 (MH ), 1433.1, 1402.5, 1297.6, 1189.6, 1123.7, 1069.5, 1015.7, 967.6, 951.4, 897.7, 977.7,
09.0, 119.0.
©
2003 NRC Canada

Li et al.
809
1
Fig. 1. Comparison of H NMR spectra (CDCl ) for 2, 4, and 5;
Fig. 2. Irradiation of 7 in CD CN.
3
3
signals of the protons belonging to ethoxyethoxy tails
(
CH CH OCH CH O -) are marked by asterisks.
3 2 2 2
with a medium pressure mercury lamp and Pyrex filter
1
(
300 nm cutoff) was monitored by H NMR by following
the disappearance of the benzylic dithianyl-CH-OH doublet.
As shown in Fig. 2, the relative intensity of the doublet de-
creases with irradiation. In our previous work, we also fol-
lowed the photofragmentation by NMR monitoring of the
release of aromatic aldehydes (4). In the present study, while
we see formyl singlets appearing in the NMR spectrum of
the irradiated 7, the aldehydes do not accumulate signifi-
cantly upon extended photolysis. Our rationale is that the
photoexcited benzophenone, being tethered in close proxim-
ity, oxidizes the liberated aldehyde. The overall efficiency of
the self-sensitized photofragmentation of rosette 7 is compa-
rable to that of a simple parent adduct of benzaldehyde and
dithiane (quantum yield of about 0.12).
pled with alcohol 5 in the presence of triethylamine. We
expected that the difference in reactivity between the pri-
mary benzylic and the more hindered secondary benzylic al-
cohols will ensure chemoselectivity. It appeared, however,
that the difference in reactivities was not sufficient to com-
1
pletely shut off acylation of the latter. Judging by H NMR,
benzoylation produced several products. We speculate that
acylation of the secondary alcohol groups may have trig-
gered dehydrative ring expansion producing seven-
membered dithiepines (9) and lowering the yield of the tar-
get rosette 7.
To rule out the involvement of calixarenic framework in
sensitization of the dithiane–carbonyl fragmentation, we car-
ried out a control experiment by irradiating tetra-alcohol 5,
which lacks the benzophenone-based sensitizing units. Irra-
diation of 5 under similar conditions (medium pressure mer-
cury lamp, Pyrex filter) for 1 h produced no changes in the
1
H NMR spectrum of 5, ruling out self-sensitization by the
calixarene itself.
In summary, we have synthesized a model calixarene-
based photolabile rosette capable of self-sensitized
photofragmentation. Work is in progress in our laboratory to
assemble functional rosettes with 5-substituted dithianes car-
rying macromolecular modules, for example, modules
equipped with hydrogen bond-based elements of molecular
Direct dicyclohexylcarbodiimide-mediated coupling of 5
with benzoylbenzoic acid did not improve the yield of the
bis-adduct 7. The presence of the carbonyl group in the
sensitizer moiety precluded an alternative route to 7 via
benzoylation of the diol 4 with the subsequent addition of
dithianyl anion. Our attempt to implement this route pro-
duced a mixture of dithiane addition products to both formyl
groups and also to benzophenone carbonyls. Successful syn-
thesis of 7 was achieved via the acylation of 5 with p-
benzoylbenzoyl chloride under partial (45%) conversion
conditions. HPLC separation of the reaction mixture on a C-
3
recognition.
Ac knowle dgm e nts
Support of this research by the NIH (GM62773) is grate-
fully acknowledged.
1
8 reversed phase column (MeCN–H O, 1:1) produced
2
Re fe re nc e s
diester 7 (18% based on reacted 5) and monobenzoylated
adduct 6 (25%).
Having isolated the diastereomers 7, we then proceeded
with photochemical studies. Irradiation of 7 in acetonitrile
1
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Supplementary data may be purchased from the Depository of Unpublished Data, Document Delivery, CISTI, National Research Council
Canada, Ottawa, ON K1A 0S2, Canada (http://www.nrc.ca/cisti/irm/unpub_e.shtml for information on ordering electronically).
©
2003 NRC Canada

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