Photooxygenation catalysis with a polyol-decorated disc-shaped porphyrin sensitizer: Shell-recognition effects

Article abstract of DOI:10.1002/adsc.200800282

Polar meso-tetraarylporphyrins 2-4 were synthesized from tetrakis-4-hydroxyphenylporphyrin 1 as the central building block by consecutive base-induced reactions with glycidol. The decorating units form a polar hydrogen-bonded shell around the sensitizer c

Full text of DOI:10.1002/adsc.200800282

UPDATES
DOI: 10.1002/adsc.200800282
Photooxygenation Catalysis with a Polyol-Decorated Disc-Shaped
Porphyrin Sensitizer: Shell-Recognition Effects
Axel G. Griesbeck,a,* Mathias Schäfer,a and Johannes Uhliga
a
Department of Chemistry, University of Cologne, Greinstr. 4, 50939 Kçln, Germany
Fax : (+49)-221-470-5057; e-mail: griesbeck@uni-koeln.de
Received: May8, 2008; Revised: July12, 2008; Published online: August 25, 2008
Abstract: Polar meso-tetraarylporphyrins 2–4 were
synthesized from tetrakis-4-hydroxyphenylporphyr-
in 1 as the central building block byconsecutive
base-induced reactions with glycidol. The decorat-
ing units form a polar hydrogen-bonded shell
around the sensitizer core which is proposed as the
binding site for polar substrates in photocatalyzed
oxygenation reactions. As substrate, the polarity-
sensor mesitylol (5) was applied and the reaction
constrained in a polystyrene matrix. Increasing shell
dimensions lead to increased diastereoselectivities
for the allylic hydroperoxides 6 and thus clearly
demonstrate the concept of shell-induced substrate
stereoselectivityin singlet oxygen reactions.
occur repeatedlywithout photobleaching of the sensi-
tizer. On the other hand, 1O2 lifetimes are high
enough to establish long diffusive path lengths sepa-
rating the areas of sensitization and reaction bysever-
al hundreds of nanometers. Even in a living cell, the
1
lifetime of O2 is about 3 msec which allows extensive
traveling through cell compartments.[12]
Photocatalysts that are designed to influence also
the stereochemical course of a photooxygenation, for
example, byintroduction of stereogenic elements,
suffer from a diffusive path length that is much too
high for imprinting stereochemical information on the
substrate. A solution can be the chiral template idea,
recentlyalso described for photochemical applica-
tions, combining light-absorbing unit with substrate-
binding motifs.[13] Hydrogen-bonding networks are the
most efficient glues because theyare weak enough to
release the products after reaction but strong enough
bycooperative effects to bind substrates in proper ge-
ometries. In our ongoing project on the synthesis of
new antimalarial peroxides, we have recentlydevel-
Keywords: diastereoselectivity; ene reaction; photo-
oxygenation; porphyrine catalyst; singlet oxygen
Singlet oxygen (1Dg-1O2) is the reactive oxidant in cat- oped a photochemical method for the photooxygena-
alytic type II photooxygenation and is formed by tion of allylic alcohols in polymer matrices.[14] This
energytransfer either from an electronicallyexcited
sensitizer molecule or byvarious chemical methods.
These reactions are highlyselective and show all ki-
method was applied for the synthesis of new genera-
tions of spirobicyclic[15] and bicyclic[16] 1,2,4-trioxanes
and was also studied with respect to changes in the
[1]
netic properties of pericyclic reactions,[2] with the photooxygenation diastereoselectivities.[17] Because of
most important reaction modes: ene reaction,[3] [4+ the apparent hydrogen-bonding interaction of 1O2
2][4] and [2+2] cycloaddition,[5] as well as heteroatom with allylic alcohols, the photooxygenation is highly
oxidation.[6] These modes represent efficient synthetic dependent on the environment of the substrate and
routes to a broad varietyof oxyfunctionalized prod-
shows solvent-solute interactions as well as substrate
ucts. Singlet oxygen is most conveniently generated in aggregation and competitive substrate-product aggre-
solution phase byphotochemical sensitization from
appropriate dyestuffs with high chemical stability and
gation.[18]
The following trends have been observed for the
singlet oxygen quantum yields.[7] Concerning green 1O2 reaction with chiral allylic alcohols: (a) non-hy-
chemistry concepts,[8] photooxygenation is the most drogen-bonding solvents give rise to the highest dia-
promising oxidation route with complete atom econo- stereoselectivities, (b) low conversions lead to high
my[9] when both oxygen atoms are incorporated in the diastereoselectivities indicating substrate-product ag-
final products,[10] as such the archetype reaction for gregation with increasing conversion, and (c) low sub-
[11]
solar chemistryapplications.
The disadvantage of strate concentrations also favor high diastereoselectiv-
1O2 as a reactant is its moderate lifetime: 2–3 msec in ities indicating substrate aggregation in non-polar sol-
water and several msec in non-polar halogenated sol- vents. These trends make chiral allylic alcohols excel-
vents. Thus, the generation of the excited state has to lent sensors for the solvent environment and for the
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Photooxygenation Catalysis with a Polyol-Decorated Disc-Shaped Porphyrin Sensitizer
UPDATES
Scheme 1. Porphyrin core 1 and hydroxylated derivatives 2 and 3.
interaction with other hydrogen-bonding substrate Table 1. Diastereoselectivities and conversions (in brackets)
for 5 photooxygenation (syn:anti) after 1 h of irradiation.
and product molecules, respectively. If the sensitizer
itself has a strong hydrogen-bonding capacity and the
1O2 ene reaction occurs preferentiallyin the vicinity
of the photocatalyst, the stereoselectivity is expected
to differ from solution phase experiments and serves
as an indication of the reaction area. For these experi-
ments, a non-polar solvent environment is crucial to
avoid competing hydrogen-bonding. The polystyrene
matrix was therefore considered as suitable because
the sensitizers can be covalentlyimmobilized and the
substrate environment mimics non-polar solvents such
as toluene.
Substrate
amount:
0.64 mmolgÀ1 1.2 mmolgÀ1 2.5 mmolgÀ1
14-HPP (1)
Monomer (2)
Dimer (3)
2.0:1 (47%) 2.1:1 (34%) 1.8:1 (26%)
2.5:1 (48%) 2.3:1 (34%) 2.2:1 (28%)
2.7:1 (44%)
2.2:1 (35%) 2.2:1 (26%)
Polyglycerol (4) 3.3:1 (47%) 3.0:1 (36%) 2.6:1 (18%)
Table 2. Diastereoselectivities and conversions (in brackets)
for 5 photooxygenation (syn:anti) after 3.5 h of irradiation.
We thus envisaged a sensitizer system that com-
bines high singlet oxygen quantum yields, a hydrogen-
bonding shell and an anchor for covalent binding to
the polystyrene bead matrix. The sensitizer core is tet-
rakis-4-hydroxyphenylporphyrin 1 (Scheme 1) with a
literature singlet oxygen quantum yield (determined
for ethanol solution) of FD =0.58.[19] In the solution
phase (benzene), photooxygenation of the polarity
sensor 2,4-dimethylbut-2-en-4-ol (5, mesitylol) gives a
2:1 dr with the syn-diastereoisomer syn-6 favored due
Substrate
amount:
0.64 mmolgÀ1 1.2 mmolgÀ1 2.5 mmolgÀ1
14-HPP (1)
Monomer (2)
Dimer (3)
2.2:1 (93%) 2.2:1 (73%) 2.2:1 (68%)
2.6:1 (87%) 2.6:1 (72%) 1.9:1 (65%)
2.5:1 (82%) 2.6:1 (74%) 2.3:1 (64%)
Polyglycerol (4) 3.5:1 (83%) 3.2:1 (69%) 2.8:1 (60%)
to hydrogen-bonding interaction with the reacting sin- beads, an appreciable increase in diastereoselectivity
glet oxygen molecule (Scheme 2).[20] Not much was observed.
changed when this sensitizer was bound in a polystyr-
As can be see from Table 1 and Table 2, substrate
ene matrix (Table 1 and Table 2). Subsequently, the concentrations were critical and the highest dr was
porphyrine 1 was treated with five equivalents of gly- observed for the lowest concentrations of 5 in the po-
cidol in the presence of triethylamine. Depending on lymer beads. The conversion, however, showed no
the base concentration, the mono- and disubstituted substantial influence on the diastereoisomeric ratios.
porphyrins 2 and 3, respectively, were isolated in Following a patent procedure,[21] substrate 1 was treat-
moderate yields. When embedded in polystyrene ed with an excess of glycidol and sodium hydride.
This process results in a mixture of polyol-decorated
porphyrins as indicated by the MALDI mass spec-
trum (see Experimental Section). In a broad distribu-
tion centered on penta- and hexamers, oligomers with
up to 25 glycidol units could be identified. This mix-
ture was deprotonated again and reacted with chloro-
methylated polystyrene beads to give the PS-bond
Scheme 2. Singlet oxygen reaction with mesitylol.
porphyrin 4 (Scheme 3). Photooxygenation with this
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Axel G. Griesbeck et al.
UPDATES
Scheme 3. Synthesis of the polyol-decorated porphyrin (n=20 shown).
sensitizer is possible several times without loss of ac-
tivityor changes in diastereoselectivity.
Substrate-sensitizer ratios of 500–1000 were calcu-
lated from the loading degree of the polystyrene
beads (ca. 5% in weight). With the sensitizer system
4, diastereoselectivities as high as 78:23 were detect-
ed, that is, selectivities are considerablyhigher (up to
65%) for coordinating, polyol-decorated porphyrins
in comparison with the tetrahydroxylated porphyrine
sensitizer 1. Consequently, singlet oxygen generated
bycollision energytransfer at the porphyrin site, rec-
Scheme 4. Singlet oxygen reaction with allylic alcohols:
effect of an intramolecular hydrogen bond (CCl4).
ognizes hydrogen-bonded substrates in the exterior of
the sensitizer when incorporated in a polymer net-
work. Even high conversions or high substrate con-
centrations did not alter this effect, indicating that the selective localization of a sensitizer in heterogeneous
binding sites at the sensitizer are not occupied by materials.
product molecules with progressing reaction.
What is the reason that the diastereoselectivityof
the ene reaction increases with increasing shell inter- Experimental Section
actions with the sensitizer? At first hand, one might
Chloromethylated polystyrene beads (1% divinylbenzene
copolymer, 100–200 mesh) were purchased from Acros Or-
ganics.
interpret this effect as contra-intuitive because the
syn-selectivitydecreases in protic solvents due to
competing hydrogen-bond interactions with the sol-
vent molecules. We have, however, discovered that
one additional hydrogen bond donor/acceptor as real-
ized in an unsaturated 1,3-diol, does indeed increase
Synthesis of Tetrakis-4-hydroxyphenylporphyrin (1)[22]
Freshlydistilled pryrole (12.5 g, 186 mmol) was slowly
added to 4-hydroxybenzaldehyde (22.7 g, 186 mmol) in
425 mL of refluxing propionic acid. After 30 min of vigorous
stirring the solvent was removed byvacuum distillation. The
resulting black residue was purified byflash column chroma-
tography(chloroform/ethanol, 20:1). The product was ob-
the syn-selectivityof the
1O2 ene reaction
(Scheme 4).[16] Thus, the stereoselectivitytrend as ob-
served for the polyol-substituted sensitizers is in ex-
cellent accord with the conception of a shell-induced
substrate binding and activation of allylic alcohols.
Additionally, these effects could also be useful for the tained as a purple powder; yield: 3.0 g (4.42 mmol, 9.5%).
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Photooxygenation Catalysis with a Polyol-Decorated Disc-Shaped Porphyrin Sensitizer
UPDATES
Figure 1. UV-MALDI-TOF spectrum of the polyol-porpyrin mixture 4.
1H NMR (acetone-d6, 300 MHz): d=8.93 (br, OH) 8.07 (d,
Synthesis of Polyglycerol-Bound Porphyrin (4)
8H, 2,6-phenyl-H, J=8.4 Hz), 7.30 (d, 8H, 3,5-phenyl-H,
J=8.4 Hz), 2.98 (s, 8H, b-pyrrole); IR: n=3317 (OH), 2918
(CH), 1606 (C=C), 1508 (C=C), 1170 (CO), 800 cmÀ1 (CH);
ESI-MS (HR): m/z=679.16 (100%) [MÀH+], 680.16 (66%),
681.16 (33%).
Tetrakis-4-hydroxyphenylporphyrin 1 (380 mg, 0.256 mmol)
in 12 mL dryTHF were added to sodium hydride (60% in
mineral oil, 54 mg, 2.24 mmol). The solution was heated to
658C and rac-glycidol (2.27 g, 30.3 mmol) in 5 mL of dime-
thoxyethane were added over 12 h via a syringe pump. After
evaporation of the solvent, the residue was dissolved in
methanol and recrystallized from acetone, then dried for
10 h at 50 mbar and 708C. The product was obtained as a
viscous, purple oil; yield:900 mg. 1H NMR (CD3OD,
300 MHz): d=7.90 (d, 8H, 2,6-phenyl-H, J=7.8 Hz), 7.06
(d, 8H, 3,5-phenyl-H, J=7.2 Hz), 4.45–2.70 (m, CH; CH2; b-
pyrrole); IR: n=3391 (OH), 2919–2873 (CH), 1558 (C=C),
1113–1071 cmÀ1 (CO).
UV-MALDI-TOF mass spectra were recorded in positive
polarity on an Applied Biosystems Voyager STR (Applied
Biosystems, Framingham, MA, USA) instrument equipped
with an N2-UV-laser (337 nm), delayed extraction and re-
flectron technology. MS analysis of the sample was per-
formed utilizing a saturated solution of a-cyano-4-hydroxy-
cinnamic acid (HCCA) in TFA 0.1%-ACN 80/20 as matrix,
bythe classic dried drop method: 1–2 mL of a sample/matrix
solution mixture (1:1, v/v) was deposited onto a stainless-
steel MALDI sample plate (Applied Biosystems, Framing-
ham, MA, USA) and left to dryat room temperature.
MALDI-mass spectra, resulting from the sum of 400 laser
shots, were acquired in the reflectron mode after external
calibration of the mass accuracy( ꢀ150 ppm) with a pep-
tide/protein mixture (Figure 1).
Synthesis of the Mono-glycerol Substituted Porphyrin
(2)
Tetrakis-4-hydroxyphenylporphyrin 1 (30 mg, 0.044 mmol)
and rac-glycidol (17 mg, 0.22 mmol) were dissolved in 10 mL
of dryethanol. After addition of triethlyamine (47 mg,
0.46 mmol) the mixture was refluxed for 4 h. Evaporation of
the solvent and flash column chromatographyafforded of a
purple powder; yield: 11 mg (0.015 mmol, 33%). 1H NMR
(CD3OD, 300 MHz): d=7.82 (d, 8H, 2,6-phenyl-H, J=
6.0 Hz), 7.90 (d, 8H, 3,5-phenyl-H, J=6.9 Hz), 4.20–3.35 (m,
C-H, C-H2), 3.28 (s, 8H, b-pyrrole); IR: n=3331 (OH),
2944 (CH), 1600 (C=C), 1508 (C=C), 1174 (CO), 802 cmÀ1
(CH); ESI-MS (HR): m/z=753.20 (100%) [MÀH+]: 754.20
(44%); mp >2508C.
Disubstituted porphyrin 3 was found as a side product.
Synthesis of the Di-glycerol Substituted Porphyrin (3)
Tetrakis-4-hydroxyphenylporphyrin 1 (51 mg, 0.075 mmol)
and rac-glycidol (27.8 mg, 0.38 mmol) were dissolved in
10 mL of dryethanol. After addition of triethlyamine
(47 mg, 0.46 mmol) the mixture was refluxed for 4 h. Evapo-
ration of the solvent and flash column chromatographyaf-
forded a purple powder; yield: 13 mg (0.015 mmol, 21%).
1H NMR (CD3OD, 300 MHz): d=7.72 (d, 8H, 2,6-phenyl-
H, J=7.8 Hz), 7.09 (d, 8H, 3,5-phenyl-H, J=7.8 Hz), 4.13–
3.30 (m, C-H, C-H2), 3.27 (s, 8H, b-pyrrole); IR: n=3331
(OH), 2944 (CH), 1600 (C=C), 1508 (C=C), 1174 (CO),
802 cmÀ1 (C-H); ESI-MS (HR): m/z=827.22 (100%)
[MÀH+], 828.22 (52%); mp >2508C.
Synthesis of Polymer Beads with Covalently Bound
Porphyrins 2 and 3
Chloromethylated polystyrene beads (2.10 g, 1.4–1.7 mmol
Cl/g, 1% divinylbenzene copolymer, 100–200 mesh) were
swollen in 38 mL of dryDMF for 20 min. The flask was
heated to 638C and a solution of 0.015 mmol of porphyrins
2 or 3, respectively, potassium carbonate (0.35 g, 2.53 mmol)
and 18-crown-6 (0.035 mg) in 10 mL of DMF, was added.
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Axel G. Griesbeck et al.
UPDATES
The mixture was stirred for 20 h at 638C. After cooling to
room temperature the resin was thoroughlywashed with
water, ethanol and ethyl acetate and dried for 3 h (50 mbar,
708C).
Rabeck, Singlet Oxygen Reactions with Organic Com-
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Synthesis of Polymer Beads with Covalently Bound
Porphyrin 4
Porphyrin 4 (25 mg) was dissolved in 10 mL of dryDMF
and deprotonated with sodium hydride (5 mg, 0.21 mmol).
After 1 h, chloromethylated polystyrene beads (2.50 g, mmol
Cl/g, 1% divinylbenzene copolymer, 100–200 mesh) in
10 mL of dryDMF were added and the mixture was stirred
for 3 d at 808C. After cooling to room temperature the resin
was thoroughlywashed with water, ethanol and ethyl ace-
tate and dried for 3 h (50 mbar, 708C).
General Procedure for the Photooxygenation of
Mesitylol (5) in Polystyrene Beads
A slurry of 2 g of polystyrene beads with a solution of mesi-
tylol in 20 mL of dichloromethane was dispersed on a Petri
dish (Ø 19 cm). The excess solvent was evaporated byleav-
ing the Petri dish for a few minutes in a well ventilated
hood. The sandysolid which was obtained was irradiated in
the looselycovered Petri dish bya sodium street lamp or a
halogen lamp without external cooling and without external
oxygen purging. The polymer beads were subsequently
rinsed with 3”20 mL of ether and filtered. After careful
evaporation of the solvent (no hydroperoxide decomposition
was observed when the temperature was kept <408C), the
crude product was analyzed by 1H NMR spectroscopy. As
the significant 1H NMR (300 MHz, CDCl3) signals were
used: syn-diastereoisomer: d=0.89 (t, 3H, J=7.42 Hz, 3H,
CH2CH3), 1.17–1.52 (m, 2H, CH2CH3), 1.65 (s, 3H, CH3),
3.52 (ddd, 1H, J=8.53, 8.53, 3.24 Hz, CH-OH), 4.12 (d, 1H,
J=8.53 Hz, CH-OOH), 4.97 (m, 2H, =CH2); anti-diastereo-
isomer: d=0.90 (t, 3H, J=7.42 Hz, 3H, CH2CH3), 1.17–1.52
(m, 2H, CH2CH3), 1.73 (s, 3H, CH3), 3.65 (m, 1H, CH-
OH), 4.27 (d, 1H, J=4.55 Hz, CH-OOH), 5.00 (m, 2H, =
CH2). The residual polystyrene beads could be used for fur-
ther photooxygenations without loss of activity for at least
six times.
[12] S. Hatz, J. D. C. Lambert, P. R. Ogilby, Photochem.
Photobiol. Sci. 2007, 6, 1106–1116.
[13] B. Grosch, T. Bach, in: Chiral Photochemistry, Molecu-
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Acknowledgements
[17] A. G. Griesbeck, T. T. El-Idreesy, A. Bartoschek, Adv.
Synth. Catal. 2004, 346, 245–251.
[18] A. G. Griesbeck, A. Bartoschek, J. Neudçrfl, C. Miara,
Photochem. Photobiol. 2006, 82, 1233–1240.
Financial support from the Deutsche Forschungsgemeinschaft
(DFG) is greatly acknowledged.
[19] B. Roeder, D. Naether, T. Lewald, M. Braune, C.
Nowak, W. Freyer, Biophys. Chem. 1990, 35, 303–312.
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