Organic dye photocatalyzed α-oxyamination through irradiation with visible light

Article abstract of DOI:10.1039/b924609f

Rose Bengal, an organic dye, was used as a visible light photocatalyst to investigate novel α-oxyamination reactions between 1,3-dicarbonyl compounds and a free radical (TEMPO). Compounds that are difficult to obtain such as quaternary fluorinated compounds were synthesized using this method. This visible light photocatalytic reaction can also be performed in water.

Full text of DOI:10.1039/b924609f

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Organic dye photocatalyzed a-oxyamination through irradiation with
visible light†‡
Hongjun Liu, Wei Feng, Choon Wee Kee, Yujun Zhao, Dasheng Leow, Yuanhang Pan and Choon-Hong Tan*
Received 23rd November 2009, Accepted 30th March 2010
First published as an Advance Article on the web 23rd April 2010
DOI: 10.1039/b924609f
Rose Bengal, an organic dye, was used as a visible light
photocatalyst to investigate novel a-oxyamination reactions
between 1,3-dicarbonyl compounds and a free radical
(TEMPO). Compounds that are difficult to obtain such as
quaternary fluorinated compounds were synthesized using
this method. This visible light photocatalytic reaction can
also be performed in water.
The call for sustainable development has led to increasing
interest in green chemistry and minimizing energy consumption
is an important aim of green chemistry.1 The use of abundant
sunlight as a clean source of energy in synthetic organic
photochemistry dates back to the beginning of 20th century.
However, this strategy has been widely ignored for a long time.2
One fundamental obstacle is the lack of photoactive compounds
Fig. 1 Structures of photocatalysts.
absorbing in the emission maxima of the spectral distribution
asymmetric alkylation reaction.5 Subsequently, Yoon and co-
of the sunlight reaching Earth’s surface. Another obstacle is
workers utilized the same photocatalyst in both intramolecular
the requirement for specialized photoreactors to generate high-
and intermolecular of [2+2] enone cycloadditions.6 A tin-free
intensity UV light or to concentrate natural sunlight.3 Thus,
it is particularly important to develop efficient visible light
photocatalysts for synthetic transformations.
The ability of Ru(bpy)3Cl2 (tris(2,2¢-bipyridine)-ruthenium(II)
chloride, Fig. 1) to mediate electron transfer allows it to
be a one-electron photoredox catalyst.4 It has recently been
reductive dehalogenation reaction was reported by Stephenson
et al. using a combination of Ru(bpy)3Cl2 and formic acid as the
hydrogen atom source.7 MacMillan et al. has also shown that an
iridium complex is an efficient photocatalyst in enantioselective
trifluoromethylation of aldehydes.8
Conversely, organic dyes, which are more environmen-
shown by several groups to be an excellent photocatalyst
tally friendly, cheaper and easier to prepare, present a vi-
in several reactions that are irradiated by visible light. An
able alternative to inorganic photocatalysts. In fact, several
important concept developed in these works is the use of
industrial pilot studies had been conducted with organic
inexpensive household fluorescent bulbs as the photon source,
dyes as photocatalyst.9,10 For example, the photosensitized
thereby circumventing one obstacle in the use of sunlight – its
oxygenation (or Schenck ene reaction) of citronellol and
variable irradiation strength and time. Nicewicz and MacMillan
1,5-dihydroxynaphthalene were studied using Rose Bengal
demonstrated that Ru(byp)3Cl2, when used in combination
(Fig. 1).10a Concentrated sunlight from special solar collectors
with an imidazolidinone organocatalyst, promotes a direct
was needed in the development of these solar-chemical reactions.
Organic dyes as photocatalysts can also be used in conjunction
with ultraviolet light from 419 nm Rayonet lamps.11 We are
interested in the development of new reactions using organic
dyes as photocatalyst in the presence of an inexpensive and
convenient source of photon – household fluorescent bulbs.
a-Oxyamination of aldehydes is a powerful transforma-
tion in organic synthesis.12 This radical-mediated reaction
involved cationic radical intermediates which were generated
by either transition-metal oxidants (Fe3+)12a or electrochemi-
cal oxidation.12b a-Oxyamination between 1,3-dicarbonyl com-
pounds and the free radical, 2,2,6,6-tetramethylpiperidine-1-
oxyl (TEMPO) has only been reported using a two step
method.13 Herein, we report a metal-free and environmentally
friendly a-oxyamination reaction with organic dyes as visible
light photocatalysts.
Department of Chemistry, 3 Science Drive 3, National University of
Singapore, Singapore 117543. E-mail: chmtanch@nus.edu.sg
† Electronic supplementary information (ESI) available: [General pro-
cedures for organic dye photocatalyzed a-oxyamination, spectroscopic
data and results of computational studies]. See DOI: 10.1039/b924609f
‡ General experimental protocol for organic dye photocatalyzed a-
oxyamination through irradiated with visible light: To a clear vial, 2
TEMPO (7.8 mg, 0.05 mmol), Rose Bengal (2.5 mg, 0.00025 mmol), a
stirring bar and distilled CH3CN (0.5 mL) were added in this sequence.
After stirring at room temperature for a while, ethyl benzoylacetate
1a (9.0mL, 0.05 mmol) was added to the mixture in one portion.
Subsequently, the vial was put under an 11 W household fluorescent
bulb. After the reaction was completed in 24 h, the reaction mixture
was concentrated and loaded onto a short silica gel column, followed by
flash chromatography. Product 3a (16.8 mg) was obtained as colorless
oil in 97% yield.
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Table 1 a-Oxyamination reactions between b-ketoeseter 1a and
TEMPO
Table 2 Substrate scope of visible light irradiated a-oxyamination
reactions
Entry
1
Ar
3
Time/h
Yield/%a
Entry
Dye
Solvent
Conv./%a
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
Ph
3a
3b
3c
3d
3e
3f
24
40
28
5
18
19
97
95
84
64
64
67
1
2
3
4
5
6
7
8
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Basic Blue 9
Rhodamine B
TPP
CH2Cl2
THF
26
30
0
100
9
34
4
7
4-MeOPh
3-MePh
3-NO2Ph
4-ClPh
4-FPh
Toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
a Isolated yield.
NKX-2553
Ru[(bpy)3]2+
None
9
10
11
7
0
0
Rose Bengalb
Table 3 Visible light photosyntheses of quaternary fluoro compounds
a Conversion was determined by 1HNMR. b Reaction was performed in
dark.
In our preliminary study, we utilized an 11 W household
fluorescent light bulb as the visible light source, which operates
within a wide spectral window (~400 to 700 nm). However,
fluorescent light bulb provided a line-like spectral distribution,
different from that of sunlight. Rose Bengal (RB), which has
a strong absorption band in the range of 500–600 nm,14 was
efficient in catalyzing the a-oxyamination reaction between b-
ketoester 1a and TEMPO 2 to give the product 3a (Table 1).
During the optimization process, we found that solvents have a
great effect on the reactivity of this reaction (Table 1, entries
1–4). Acetonitrile was shown to be the best solvent for the
photocatalysis reaction (Table 1, entry 4).
Further investigations were conducted using other organic
dyes like Basic Blue 9, Rhodamine B and meso-tetraphe-
nylporphine (TPP) (Fig. 1 and Table 1, entries 5–7). In most
examples, only low conversions were observed. A polyene
dye 2-cyano-5-(4-dimethylaminophenyl)penta-2,4-dienoic acid
(NKX-2553) (Fig. 1),15 which was demonstrated to be an effi-
cient dye for dye-sensitized solar cells, also gave low conversion
(Table 1, entry 8). Surprisingly, the common organometallic
photocatalyst, Ru(byp)3Cl2, gave a low conversion of 7%
(Table 1, entry 9). In the absence of either the photocatalyst or
light source, no product was obtained (Table 1, entry 10 and 11).
Subsequently, the substrate scope of the a-oxyamination
reactions was examined. Complete reactions were observed and
excellent isolated yields were obtained for the coupling products
3a–c (Table 2, entry 1–3). A strong electron donating group
on the aromatic ring will lead to slower reaction rate (Table 2,
entry 2). In contrast, a faster reaction was observed for a strong
electron deficient aromatic b-ketoester 1d (Table 2, entry 4).
However, only 64% yield was obtained due to the decomposition
of the product 3d. Alkyl ketone esters did not give any products.
There is a strong demand for fluorinated compounds as
they are often used as leads and building blocks in medicinal
chemistry.16 The preparation of quaternary fluorinated com-
pounds is particularly difficult and interesting. As far as we
know, a general method for the synthesis of a-fluorinated a-
Entry
4
Ar
5
Time/h
Yield/%a
1
2
3
4
5
4a
4b
4c
4d
4e
Ph
5a
5b
5c
5d
5e
30
40
18
27
19
88
88
95
91
90
4-MeOPh
3-NO2Ph
4-ClPh
4-FPh
a Isolated yield.
hydroxy acid derivatives is not available. We recently reported
guanidine-catalyzed formation of highly enantioselective and
diasteroselective chiral quaternary C–F bond through conjugate
addition and Mannich reactions using a-fluoro-b-ketoesters
as the fluorocarbon nucleophiles.17 Using similar fluorocarbon
nucleophiles, a-fluoro-b-ketoesters 4a–e, a series of quaternary
a-fluorinated a-hydroxy acid derivatives 5a–e were synthesized
with high yields using this new methodology (Table 3). The
reaction rates of the electron deficient aromatic a-fluoro-b-
ketoesters were faster than that of the electron rich ones. To
our best knowledge, this is the first report on the synthesis of
a-fluorinated a-hydroxy acid derivatives.
With the optimized condition, we screened other substrates
for this photocatalytic a-oxyamination reaction. 1,3-Diketone
6 was efficiently converted to the corresponding adduct 7 with
67% yield (Scheme 1). Similarly, the nitro-ketone compound 8
exhibited an extremely fast reaction and gave adduct 9 with 72%
yield (Scheme 1).
Interest in aqueous photochemistry generally revolved around
these main themes: the photodegradation of aromatic com-
pounds in the atmosphere, photocatalysis as a method to
treat hazardous wastewater and more recently, photocatalytic
splitting of water.18 However, this can also potentially be an
interesting technique for the selective and clean transformation
of organic chemicals. So far the only example for aqueous
photosynthesis of compounds utilized ultraviolet light. Excellent
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(RB) accepted a photon from the visible light to form RB*; as
a reductant, it transferred an electron to the substrate 1 via a
single electron transfer process (SET). Rose Bengal was recycled
via another SET process from the electron rich intermediate 11.
The radical 12 was coupled with free radical TEMPO to give the
product 3.
Using DFT calculations performed at M06-2X level of theory
using Gaussian 09 program, we found that the electron affinity
(EA) of aromatic b-ketoesters 1 was positive. The anion 10
can exist sufficiently long enough and the SET process was
favorable.19b In contrast, the EA of alphatic b-ketoesters was
negative in the SET process, suggesting alphatic keto-ester is
not suitable for the a-oxyamination reaction which matches the
experimental results. In addition, the LUMO’s energy level of
alphatic b-ketoesters was much higher than that of aromatic
keto-ester. We are currently still investigating the detailed
mechanism of this reaction.
Scheme 1 Applications of photocatalysis of a-oxyamination reactions.
yield of adduct 3a was obtained when the experiment was
conducted in water (Scheme 2) and the reaction was essentially
similar to the example in CH3CN (Table 2, entry 1).
In conclusion, we have developed an organic dye, Rose Bengal,
photocatalyzed C–O coupling reaction through the irradiation
of visible light. This method was applied to the synthesis of
a variety of a-hydroxy acid derivatives with excellent yields
and also to the synthesis of quaternary a-fluorinated a-hydroxy
acid derivatives. We have also successfully demonstrated that
this photocatalytic reaction can be conducted in water in the
presence of visible light.
Scheme 2 Visible light mediated a-oxyamination in water.
As a demonstration of the scalability of this visible light driven
photocatalytic process, we performed the a-oxyamination using
the ambient sunlight on the roof of our laboratory building and
obtained 150 mg of 3a (Scheme 3). The same experiment was
also conducted under laboratory condition using fluorescent
light bulb with the same result.
Acknowledgements
This work is supported by ARF grant (R-143-000-337-112),
research scholarships (to H. L., D. L. and Y. P.) from the
National University of Singapore. We thank the Medicinal
Chemistry Program for their financial support.
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As Rose Bengal is well known as a singlet oxygen sensitizer, we
conducted control experiments in a glove box to verify the role of
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