Thiaporphyrin-mediated photocatalysis using red light

Article abstract of DOI:10.1039/c6ra11374e

Penetration of light through biological tissue improves in the near-IR windows beyond 650 nm. In an effort to explore the chemical reactivity accessible using this low-energy radiation, this study reveals catalysts and reactions that are experimentally viable with red light. Thiophene-containing porphyrin compounds are capable of catalytic, photo-reductive dehalogenation on an array of α-halo ketone model substrates with low catalyst loadings (0.1 mol%), in the presence of low energy, red light (>645 nm).

Full text of DOI:10.1039/c6ra11374e

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Thiaporphyrin-mediated photocatalysis using red
light†
Cite this: RSC Adv., 2016, 6, 59269
JinGyu Lee,‡ James W. Papatzimas,‡ Ashley D. Bromby, Evgueni Gorobets
and Darren J. Derksen*
Received 2nd May 2016
Accepted 14th June 2016
DOI: 10.1039/c6ra11374e
www.rsc.org/advances
Penetration of light through biological tissue improves in the near-IR
windows beyond 650 nm. In an effort to explore the chemical reac-
tivity accessible using this low-energy radiation, this study reveals
catalysts and reactions that are experimentally viable with red light.
Thiophene-containing porphyrin compounds are capable of catalytic,
photo-reductive dehalogenation on an array of a-halo ketone model
substrates with low catalyst loadings (0.1 mol%), in the presence of low
energy, red light (>645 nm).
Photo-mediated reactions have reemerged in synthetic chem-
1
istry as powerful tools to form and break chemical bonds. With
major advances in the eld, most light-mediated synthetic
chemistry utilizes high energy blue or green light (375–570 nm).
Recent developments in proximity-directed chemistry and
photochemical release or activation of bioactive molecules,
have validated the approach of using light to probe and interact
2,3
with biological systems. The most commonly used photo-
catalysts in the eld are ruthenium and iridium based poly-
pyridyl complexes which absorb photons in the blue region of
4–6
7
the visible spectrum (Fig. 1). Organic dyes such as eosin Y
and rose bengal, which absorb in the green region, have also
been reported in literature to be used as photocatalysts and
8,9
show signicant promise for synthetic applications. Aer
identication of the synthetically tunable, thiophene-
containing porphyrin scaffold, we decided to explore the pho-
toreductive properties of meso-5,10,15,20-tetraphenyl-21-
monothiaporphyrin (S1TPP), and 5,10,15,20-tetraphenyl-21,23-
dithiaporphyrin (S2TPP) due to their absorbance properties at
wavelengths beyond 650 nm and moderate excited state
1
0–13
reduction potentials (ꢀ0.586 to ꢀ0.741 eV).
Recent reports
have also shown that S2TPP-related compounds, together with
oxygen, have potential as light-activatable drug delivery systems
Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary,
Alberta, T2N 1N4, Canada. E-mail: dderksen@ucalgary.ca
8
†
1
‡
Electronic supplementary information (ESI) available. See DOI:
0.1039/c6ra11374e
Fig. 1 Absorption properties of commonly used photocatalysts.
These authors contributed equally.
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14
using ‘photo-unclick’ chemistry. Based on our interest in irradiation (25% yield) that remained unchanged aer an
exploring low-energy light reactivity within biological microen- additional 17 hours in the dark (data not shown). Using the
vironments, it was necessary to complete a model study on the same model system, the addition of 5 eq. of TEMPO resulted in
reductive, bond-cleaving reactions that can occur using consumption of the Hantzsch ester and complete recovery of
thiophene-containing porphyrins.
bromoacetophenone aer 1 h. These results are not consistent
We selected dehalogenation as a model system for exploring with a radical chain reaction but instead support a typical
the use of red light for metal-free, photoreductive catalysis photo-catalytic mechanism mediated by a hydrogen atom
1e
(
3 2
Table 1). It was observed that alone, Ru(bpy) Cl had very low transfer agent (Scheme 1). Note that the dehalogenation
reactivity under long wavelength light (entry 1). Combining model reaction of bromoacetophenone is complete within 1 h
Hantzsch ester (HEH) and Ru(bpy) Cl provided a modest (73%) under the standard reaction conditions and is unaffected
3
2
increase in yield (entry 2) above the reactivity of HEH without by the addition of 1 equivalent of water (74%). With the intent of
15
catalyst (entry 3). The addition of N,N-diisopropylethylamine reaching a balance between practicality and product yield, we
DIPEA) ensured consistent pH levels in the optimization reac- selected a standard reaction time of 18 h to ensure low levels of
(
tions. Omission of catalyst and HEH resulted in a very low level substrate reactivity were not overlooked. Building on these
of background dehalogenation (entry 4). In the absence of preliminary results, we investigated the substrate scope on an
catalyst and base, the background reactivity of HEH was array of a-functionalized carbonyl-containing compounds
observed (entry 5). We immediately observed improved deha- (Table 2). The inuence of steric hindrance on dehalogenation
logenation reactivity for S1TPP and S2TPP beyond reactions efficiency for the thiophene-containing catalysts was evident
using Ru(bpy) Cl at 0.1 mol% loading (entry 6,7). DIPEA plays based on decreasing isolated yields due to lower conversion and
3
2
a role in effective photocatalysis as reactions with only catalyst reduced reaction rates (entries 1–6). This analysis also revealed
and HEH resulted in a decrease in yield (entry 8, 9). In combi- a trend that when S2TPP was used as the catalyst, isolated yields
nation with HEH, and base, yields of thiophene-mediated red were consistently lower than S1TPP (40–60% vs. 75–90%
light dehalogenation improved dramatically (entry 10, 11). respectively). These differences in reactivity are attributed to the
10
Alternative bases triethyl- and tributyl amine were less effective stronger reduction potential, and marginally better solubility
than DIPEA (entry 12, 13) while the biomimetic NADH analog, 1- properties, of S1TPP. With reliably better yields, S1TPP was
benzyl-1,4-dihydronicotinamide (BNAH), was the only alternate selected for further evaluation. Other halogens were also eval-
hydrogen atom source that provided effective reactivity – formic uated for reactivity under the optimized red-light conditions
acid was ineffective in the reaction conditions (entry 14,15). To (entry 7, 8). Although chloroacetophenone showed some reac-
explore the possibility of a radical chain reaction-type mecha- tivity in the red-light optimized conditions, the rate of reaction
nism, the reaction yield for bromoacetophenone under stan- and corresponding conversion are considerably lower than for
dard conditions was determined aer 5 minutes of red-light bromoacetophenone. Similarly, the more labile iodoacetophe-
none reacted quantitatively, clearly demonstrating the effect of
substrate bond-strength on the catalytic reactivity. No reactivity
Table 1 Catalyst and reaction optimization
was observed on analogous ester or amide-derived substrates
entry 9, 10). Notably, under the standard reaction conditions,
(
b
Entry
Catalyst
Base
H-Atom source
Yield [%]
1
2
3
4
5
6
7
8
9
Ru(bpy)
Ru(bpy)
No catalyst
No catalyst
No catalyst
S1TPP
S2TPP
S1TPP
S2TPPa
S1TPPa
S2TPP
3
Cl
Cl
2
DIPEA
DIPEA
DIPEA
DIPEA
None
DIPEA
DIPEA
None
None
HEH
HEH
None
HEH
None
None
HEH
HEH
HEH
HEH
HEH
HEH
3
18
13
3
a
3
2
21
26
25
13
10
75
72
45
45
2
None
DIPEA
DIPEA
10
11
12
13
14
15
S1TPP
S1TPP
S1TPP
S1TPP
Et
Bu
3
N
3
N
DIPEA
DIPEA
2
HCO H
BNAH
58
a
Standard conditions: 0.1 mol% catalyst, 1.1 eq. Hantzsch ester (HEH),
eq. DIPEA, DMF, 18 h, rt. Yield determined through analysis with
b
2
GC-MS.
Scheme 1 Proposed mechanism adapted from MacMillan and cow-
orkers. HEH ¼ Hantzsch ester, SET ¼ single electron transfer.
1e
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Table 2 Study of reaction scope for isolated yields on 1 mmol scale
Entry Substrate
Product
% yield Entry Substrate
Product
% yield Entry Substrate
Product
% yield
86
1
90
78
7
8
12
13
14
2
3
Quant
85
76
80
92
75
60
60
9
10
11
NR
NR
15
16
17
b
4
b
c
5
16
b
6
40
12
40
18
98
a
16
b
c
Yield of puried product on 1 mmol scale.
S2TPP used as catalyst. Yield determined through GC-MS analysis due to volatility of product. NR ¼
0
no reaction, adam ¼ adamantyl, biphenyl ¼ 1-(1,1 -biphenyl)-4-yl.
alkyl halo-ketones (entry 11, 12), also displayed modest photochemically altering chemical bonds using light beyond
conversion to the corresponding methyl ketones. There appears 645 nm, deep into the red wavelengths of light. Further inves-
to be no inherent correlation between electronic effects of tigations toward expanding the substrate scope, and exploring
substituents as the overall yield is comparable for electron chemoselectivity of the modied thiophene-containing
donating or withdrawing substituents (entry 13, 14). Aryl- porphyrins are currently underway.
bromides and nitriles remain compatible with the reaction
conditions (entry 15, 16). The position of aryl functional groups
and the effect of extended conjugation on reactivity were also
Acknowledgements
explored (entry 17, 18). No by-products were detected during the
The authors wish to thank the Alberta Children's Hospital
course of our investigations, highlighting the advantage of
Research Institute, the Alberta Children's Hospital Foundation,
using low energy photons for chemoselective bond cleavage. We
the Charbonneau Cancer Institute and University of Calgary for
have shown that thiophene-containing porphyrin catalysts are
their support of this research. Thanks to Mr Wade White and
capable of directly catalyzing a modest scope of photo-reductive
Mr Jian Jun Li in the University of Calgary, Department of
dehalogenation reactions using low energy red light above 645
Chemistry Instrumentation Lab. The authors would also like to
nm. In contrast to many other photocatalytic dehalogenation
thank Dr Todd Sutherland and Dr Belinda Heyne for helpful
reactions, this method does not require expensive transition
discussions in the development of this work.
metal catalysts for these dehalogenations to occur. Given the
success of red-light mediated methods emerging in the recent
literature, the further exploration of thiophene-based porphy- Notes and references
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ꢂ
ꢂ
reported at rt remained at a temperature of 22 C ꢃ 2 C
over the course of the reaction.
59272 | RSC Adv., 2016, 6, 59269–59272
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