Metal-free photocatalytic radical trifluoromethylation utilizing methylene blue and visible light irradiation

Article abstract of DOI:10.1021/cs5005823

The use of organofluorine compounds, especially those with an incorporated trifluoromethyl moiety, has increased dramatically in both the pharmaceutical and agrochemical industry. It has therefore become imperative to develop a mild and efficient synthetic technique for the inclusion of trifluoromethyl groups. Herein, we report the first use of methylene blue as a photosensitizer for the catalytic radical trifluoro- and hydrotrifluoromethylation of electron-rich heterocycles as well as terminal alkenes and alkynes under visible light irradiation. These reactions proceed with moderate to good yields at low catalyst concentrations; short irradiation times; and most importantly, without the need for potentially toxic transition-metal catalysts. In this work, considerable emphasis was also placed on understanding the kinetics of the mechanistically key steps through the use of laser flash photolysis techniques to more efficiently optimize the reaction conditions.

Full text of DOI:10.1021/cs5005823

Research Article
pubs.acs.org/acscatalysis
Metal-Free Photocatalytic Radical Trifluoromethylation Utilizing
Methylene Blue and Visible Light Irradiation
Spencer P. Pitre, Christopher D. McTiernan, Hossein Ismaili, and Juan C. Scaiano*
Department of Chemistry and Centre for Catalysis Research and Innovation, University of Ottawa, 10 Marie Curie, Ottawa K1N
6N5, Canada
S
* Supporting Information
ABSTRACT: The use of organofluorine compounds, espe-
cially those with an incorporated trifluoromethyl moiety, has
increased dramatically in both the pharmaceutical and
agrochemical industry. It has therefore become imperative to
develop a mild and efficient synthetic technique for the
inclusion of trifluoromethyl groups. Herein, we report the first
use of methylene blue as a photosensitizer for the catalytic
radical trifluoro- and hydrotrifluoromethylation of electron-
rich heterocycles as well as terminal alkenes and alkynes under
visible light irradiation. These reactions proceed with moderate to good yields at low catalyst concentrations; short irradiation
times; and most importantly, without the need for potentially toxic transition-metal catalysts. In this work, considerable emphasis
was also placed on understanding the kinetics of the mechanistically key steps through the use of laser flash photolysis techniques
to more efficiently optimize the reaction conditions.
KEYWORDS: trifluoromethylation, metal-free, methylene blue, photoredox catalysis, laser flash photolysis
INTRODUCTION
■
Over the years, the impact of organofluorine compounds on
both the pharmaceutical and agrochemical industries has grown
exponentially.1,2 In particular, the trifluoromethyl (CF3) group
is becoming one of the most structurally important moieties in
these fields. Incorporation of fluorine atoms, in particular CF3
moieties, can lead to an increase in bioavailability, lipophilicity,
metabolic stability, and hydrolytic stability in compounds in
comparison with their nonfluorinated counterparts.3 Consider-
ing that organofluorine compounds are virtually absent in
nature, developing a mild, efficient synthetic method for the
inclusion of a CF3 group is of utmost importance.
In the past five years, the development of methods for the
direct replacement of C−H bonds with C−CF3 bonds has
attracted a great deal of attention.4 For example, MacMillan and
co-workers have developed a highly efficient photocatalytic
technique for the trifluoromethylation of a variety of different
substrates based on ruthenium and iridium complexes using
various CF3 precursors.5−8 Employing a similar system, Cho
and co-workers have also demonstrated the trifluoromethyla-
tion of a variety of electron-rich heterocycles (see Figure 1A).9
Figure 1. Trifluoromethylation of electron-rich heterocycles and
Ruthenium complexes along with Umemoto’s reagent have also
been recently shown to catalyze the hydrotrifluoromethylation
of a broad scope of unactivated terminal alkenes and alkynes
(see Figure 1B).10 A major limitation of these methods is the
use of precious metals as photocatalysts, which can exhibit high
toxicity and thus limit their further applications in the
pharmaceutical and agrochemical industries. Alternatively to
these photochemical methods, these transformations can be
achieved with the use of other transition-metal catalysts.11 For
unactivated alkenes.5,9,10,12,13
example, Buchwald and Wang have independently developed
efficient methods for the trifluoromethylation of unactivated
Received: April 30, 2014
Revised: June 12, 2014
Published: June 13, 2014
© 2014 American Chemical Society
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alkenes employing different copper(I) catalysts and Togni’s
Reagent as the CF3 source (see Figure 1C) and have provided
experimental evidence that free CF3 radicals were involved in
these transformations.12,13 However, these transformations
typically require a high concentration of the copper(I) catalyst
(10−15 mol %), and the method developed by Wang and co-
workers also requires the input of heat into the system to
obtain high reaction efficiency.
In light of the disadvantages associated with these transition-
metal catalyzed methods, there has been a recent push to
develop a novel transition-metal-free catalytic system for these
trifluoromethylation transformations.14−20 However, the use of
metal-free systems in this field still remains rather under-
developed. On the basis of our previous results for the oxidative
hydroxylation of arylboronic acids using methylene blue (MB)
as photosensitizer,21 we decided to test MB as a photosensitizer
for the radical trifluoromethylation of various substrates. MB is
a member of the thiazine dye family and, as previously
demonstrated, has a triplet state that is readily quenched by
aliphatic amines to form a semireduced MB radical and an
amine-radical cation (Scheme 1). In this case, both the
RESULTS AND DISCUSSION
■
Because of the electrophilic nature of the CF3 radical, we chose
to begin our studies of radical trifluoromethylation employing
MB as a photocatalyst for the trifluoromethylation of electron-
rich substrates using 3-methylindole (3MI) as our model
substrate. Recently, Cho and co-workers reported the
trifluoromethylation of 3-methylindole with Ru(bpy)3Cl2 as
the photosensitizer and CF3I as the CF3 radical source.9 One
limitation of this method, however, is the use of CF3I, which is
a gas. This makes it difficult to know the exact concentration
present in the reaction mixture, making it difficult to optimize
the kinetics of key reaction steps, something we emphasize in
this contribution. With this in mind, we decided to employ
electrophilic CF3 reagents, such as Togni’s hypervalent-iodine
compounds and Umemoto’s reagent, for the trifluoromethyla-
tion of 3-methylindole.
First, the role of the amine “electron-donor” was examined.
The trifluoromethylation of 3-methylindole was attempted with
MB and Togni’s reagent (II) (see reaction 1 and Table 1) using
Scheme 1. General Scheme for Photoredox Transformations
Catalyzed by a Methylene Blue/Amine Photocatalytic
System
Table 1. Substrate Screening for the Trifluoromethylation of
3-Methylindole
triethylamine (TEA), N,N-diisopropylethylamine (DIPEA),
and N,N,N′,N′-tetramethylenediamine (TMEDA, reaction 1)
as the electron donors. We were pleased to observe the
trifluoromethylated product in every case; however, when
TMEDA was used as the electron donor, the highest yield was
obtained (see S3 in the Supporting Information (SI)). This
was, however, no surprise; we had found earlier that TMEDA
has the highest rate constant for the quenching of MB’s triplet
state of the three amines chosen, which produces the
semireduced MB radical, and an amine-radical cation.21
We then proceeded to screen which electrophilic CF3 source
would provide the most efficient generation of CF3 radicals. We
had initially hypothesized that Umemoto’s reagent (Table 1,
left) would be the most efficient source of CF3 radicals because
it has a much lower reduction potential than both analogues of
Togni’s reagent (Table 1).23 However, after 24 h of irradiation,
we observed that the reaction with Togni’s reagent (I) was the
most efficient at 77% yield, whereas the reaction with
Umemoto’s reagent was the least efficient of the three sources.
Although this puzzled us initially, a detailed look at the kinetics
for the triplet quenching of MB provided us with an answer.
semireduced MB and the amine-radical cation, which readily
deprotonates to form an α-aminoalkyl radical under basic
conditions, are capable of reducing numerous organic
substrates.21,22 With this knowledge, we aimed to develop a
mild trifluoromethylation method based on a system in which
MB and the α-aminoalkyl radicals could be used to reduce
several electrophilic CF3 sources and thereby produce the
required CF3 radicals (see Figure 1D).
Herein, we report the first use of MB as a photocatalyst,
coupled with Togni’s reagent as the CF3 source, for the radical
trifluoromethylation of electron-rich heterocycles, as well as the
hydrotrifluoromethylation of terminal alkenes and alkynes
under visible light irradiation. In this work, considerable
emphasis was placed on understanding the kinetics of the
mechanistically relevant steps using laser flash photolysis
techniques to more efficiently optimize our reaction conditions.
Rate constants for these steps have also been determined.
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Rather than provide extensive details for all the rates measured,
we describe briefly below the type of measurements carried out
by laser flash photolysis, and all other details (for other
systems) are part of the Supporting Information.
interpretation would not be possible without an in-depth
kinetic analysis.
With the optimal substrates in hand, we then focused on
optimizing the reaction conditions. As seen in Table 2, the rate
Figure 2 shows the data used to determine the rate constant
for TMEDA quenching of triplet MB. Because of the overlap in
Table 2. Optimization of Reaction Conditions
MB, mM TMEDA, mM
solvent
atm
air
time, h isolated yield
0.3
0.3
0.6
1.2
2
60
60
CH3CN
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
12
6
25%
air
23%
120
120
200
200
200
air
9
44%
air
6
59%
air
6
59%
3
Figure 2. Kinetic analysis of the reaction between MB and TMEDA.
2
argon
argon
argon
argon
6
70%
Because of overlap between signals corresponding to the triplet and
6
trace
35%
3
reduced form of MB, the rate of MB quenching was measured by
2
2
6
monitoring the recovery of ground state MB at 650 nm. (A) Decay
traces measured at 650 nm in the presence of 0 mM (black) and 0.13
mM (red) TMEDA after laser pulse excitation (308 nm, 10 mJ) of
MB. Traces were normalized to account for permanent bleaching of
a
200
6
no reaction
a
Reaction performed in the dark.
3
the sample. (B) Kinetic plot showing the rate of MB quenching as a
of the reaction was found to increase when the solvent was
switched from CH3CN to DMF. The reaction rate also
increased proportionally when increasing the concentration of
MB. Finally, removing O2 from the reaction (3MB kq = 2.46 ×
109 M−1 s−1)21 resulted in an 11% increase in yield as a result of
the removal of this competing triplet quenching process.
Control experiments also showed that both MB and visible
light irradiation are required for the trifluoromethylation of 3-
methylindole. Interestingly, trifluoromethylation was observed
in the absence of TMEDA, yielding 35% of the trifluoromethy-
function of [TMEDA]. The slope of this plot corresponds to the
bimolecular rate constant for this reaction (3.41 × 108 M−1 s−1).
signals for triplet MB and its reduced form, we measured the
rate by monitoring the recovery of the ground state band from
MB at 650 nm following 308 nm laser excitation. The two
traces shown correspond to the lowest (0 mM) and highest
(0.13 mM) concentrations of TMEDA in the kinetic plot of
panel B. From the slope in panel B, one derives the bimolecular
quenching rate constant.
A procedure similar to that illustrated in Figure 2 was
employed to determine various rate constants. As shown in
Table 1, we also investigated the quenching constants (kq) for
all substrates and products in our model reaction. For this
reaction to proceed efficiently, TMEDA must out-compete the
other substrates for quenching of MB’s triplet state so as to
generate the active catalytic components.
We found that Umemoto’s reagent quenches the triplet of
MB 2 orders of magnitude faster than Togni’s reagent (I),
which probably accounts for the large difference in reactivity
observed. To put this into perspective, we can formulate the
following equation to determine the percentage of TMEDA
quenching MB’s triplet state at initial reaction conditions.
lated indole. Upon further investigation, it was discovered that a
ox
single electron transfer from 3-methylindole (E = 1.12 V vs
1/2
SCE)24 to the triplet state of MB (E = 0.011 V vs SCE for
red
1/2
ground-state MB)25 is a thermodynamically favorable process
when the triplet state energy of MB (33 kcal/mol)26 is taken
into account. The high triplet-quenching constant (4.1 × 108
M−1 s−1) also makes it a kinetically favorable process upon
removal of TMEDA. Therefore, upon removal of TMEDA,
3
electron-transfer occurs to MB from 3-methylindole, resulting
in an oxidized indole and the semireduced form of MB. Because
we do not isolate any other products after the reaction, we
hypothesize that the oxidized indole could be reduced back to
its original form by the trace amounts of amine impurities in
the solvent.27 In addition, we have previously observed that
21
3
these amine impurities can also reduce MB. This could
explain why the percent yield is roughly half of that measured
when our sacrificial amine is present in the reaction mixture.
With these final optimized conditions, we proceeded with the
radical trifluoromethylation of various electron-rich hetero-
cycles (Table 3) utilizing the same optimized conditions for the
trifluoromethylation of 3-methylindole. The trifluoromethyla-
tion of various substituted indoles proceeded with high
efficiency. No trifluoromethylation of the aromatic portion of
the indole substrates was observed. The trifluoromethylation of
pyrroles as well as a thiophene derivative also proceeded in
moderate yields.
%TMEDA quenching =
100% × kqTMEDA[TMEDA]
(τ0−1 + kqTMEDA[TMEDA] + kq3MI[3MI] + kqCF source[CFsource] + kqO2[O2])
3
3
By performing this calculation for both Umemoto’s reagent
and Togni’s reagent (I) for a CF3 source concentration of 45
mM, we determined that only 8% of the triplets are quenched
by TMEDA for the reaction containing Umemoto’s reagent, as
compared with 51% of the triplets for the reaction containing
Togni’s reagent (I). Therefore, even though Umemoto’s
reagent has a much lower reduction potential than the
hypervalent iodine compounds, it is still less efficient for
radical trifluoromethylation with MB because it inhibits the
quenching of the triplet by TMEDA. Note that this mechanistic
We then shifted our attention to the trifluoromethylation of
unactivated terminal alkenes. Currently, the methods available
for alkenyl trifluoromethylation are limited to narrow substrate
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Table 3. Trifluoromethylation of Electron-Rich Substrates
Table 4. Trifluoromethylation of 1-Dodecene
Conditions: 1-dodecene (95 mM), Togni’s Reagent (1.5 equiv), MB
(0.02 equiv), amine (2 equiv) in DMF were irradiated with two warm
white LEDs.
Notably, we were also able to complete the reaction in only 3 h
using DBU. More interestingly, despite this increase in reaction
3
efficiency, the MB quenching rate for DBU is actually a full
order of magnitude less than that of TMEDA. However, it is
important to note that these quenching constants take into
account all forms of 3MB quenching because not all quenching
events result in electron transfer. Therefore, although DBU
may have a lower overall kq compared with TMEDA, it is
observed through absorption spectra that DBU forms a charge-
transfer complex with MB, resulting in improved electron
transfer (see Figure S1 in SI). To further investigate the nature
of this charge-transfer complex, a Benesi−Hildebrand analysis
was performed. From this, it was determined that a complex is
formed with an association constant (KA) of 2.5 × 104 M−1 (see
section S6 in the SI).
Conditions: substrate (100 mM), Togni’s Reagent (1.5 equiv), MB
(0.02 equiv), TMEDA (2 equiv) in DMF were irradiated with two
warm white LEDs for 6 h.
On the basis of these results, we decided to test our system in
the hydrotrifluoromethylation of both a number of different
terminal alkenes and alkynes. Gouverneur and co-workers
reported a Ru(bpy)3Cl2 photoredox catalytic method for these
transformations.10 More recently, Nicewicz and co-workers also
developed an organocatalytic hydrotrifluoromethylation proce-
dure based on an acridinium photocatalyst along with
thiosalycilate or thiophenol as a substoichiometric H-donor.18
However, these methods require high catalyst concentrations
and long irradiation times. Pleasingly, our system was able to
catalyze many of these hydrotrifluoromethylation reactions for
both terminal alkenes and alkynes (Tables 5 and 6).
Importantly, our system required lower catalyst loading while
providing improved efficiency, as well as an improved E/Z ratio
for the hydrotrifluoromethyltion of terminal alkynes as
compared with the system developed by Gouverneur (Table
6).10
With efficient methods developed for both the trifluor-
omethylation of electron-rich heterocycles and for the hydro-
trifluoromethylation of terminal alkenes and alkynes, we then
decided to test the selectivity of our system by attempting the
trifluoromethylation of 1-allyl-3-methylindole (Scheme 2).
Because of the electrophilic nature of the CF3 radical, the
radical should preferentially add to the electron-rich double
bond of the alkene moiety over the terminal alkene moiety. Not
surprisingly, we also observed minor products corresponding to
the hydrotrifluoromethylation of the terminal alkene moiety,
similarly to a recent report by Chu and Qing.31 However, from
scopes and the requirement of prefunctionalized substrates and
transition-metal catalysts.1 Because of recent work by Cho and
co-workers in their development of a photoredox method for
the trifluoromethylation of unactivated alkenes,28 we decided to
investigate the potential of our system for similar processes. 1-
Dodecene was used as a model substrate, and the
trifluoromethylation reaction was attempted under our
predetermined optimized conditions. Interestingly, not only
did we observe the product corresponding to the CF3 radical
addition to the double bond, but we also observed that the
major product of the reaction corresponded to the addition of
both a CF3 radical and a hydrogen atom to the terminal double
bond (see Table 4). Although this originally came as a surprise,
multiple hydrogen sources are available in our reaction to
promote such a transformation. For instance, it has been
reported that oxidized amines are great hydrogen donors.29 It
has also been reported that the fully reduced form of MB, leuco-
MB, can act as a hydrogen source.30 In Cho’s reported
trifluoromethylation of terminal alkenes, 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) was used as the
sacrificial electron donor for the Ru2+ excited state.28 In an
attempt to push the selectivity toward only CF3 radical
addition, we performed the reaction replacing TMEDA as the
electron donor with DBU. Surprisingly, we observed the same
distribution of the final products as the previous reaction with
TMEDA; however, with an increased efficiency (Table 4).
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hydrotrifluoromethylation of the terminal alkene is desired or
not.
Table 5. Hydrotrifluoromethylation of Terminal Alkenes
Finally, to establish if our reactions proceed with the addition
of a CF3 radical to our substrates, we added 4-hydroxy TEMPO
to our reaction mixture to trap the CF3 radical (Figure 3).
Conditions: substrate (100 mM), Togni’s Reagent (1.5 equiv), MB
(0.02 equiv), DBU (2 equiv) in DMF were irradiated with two warm
white LEDs for 3 h.
Table 6. Hydrotrifluoromethylation of Terminal Alkynes
Figure 3. CF3 radical trapping by TEMPO (top) and proposed
mechanism for the formation of CF3 radicals (bottom).
When the reaction was performed with 2 equiv of TEMPO
with respect to Togni’s reagent (I), we observed the
trifluoromethylated TEMPO in 65% yield by 19F NMR, thus
confirming the formation of CF3 radicals. A possible
mechanism for the catalytic formation of CF3 radicals is
shown in Figure 3, where upon visible light irradiation, the
triplet state of MB can be quenched by either TMEDA or DBU
to form the semireduced MB radical and an α-amino radical.
Both of these species can in turn reduce Togni’s reagent,
resulting in the release of a CF3 radical and the formation of 2-
iodobenzoate.
CONCLUSION
■
We have demonstrated for the first time the use of methylene
blue as a photosensitizer for the catalytic generation of CF3
radicals. Using this system, we have demonstrated the
trifluoromethylation of electron-rich heterocycles, which
proceeded in moderate to good yield, as well as the
hydrotrifluoromethylation of terminal alkenes and alkynes,
which proceeded with high efficiency. Our method avoids the
use of potentially toxic and expensive transition-metal catalysts
while also providing improved reaction efficiency with lower
catalyst loadings.
Conditions: substrate (100 mM), Togni’s Reagent (1.5 equiv), MB
(0.02 equiv), DBU (2 equiv) in DMF were irradiated with two warm
white LEDs for 3 h.
a
Scheme 2. Trifluoromethylation of 1-Allyl-3-methylindole
Once again, an understanding of the rate constants of the
mechanistically key steps aided in the overall optimization and
improved efficiency of our reaction conditions.
EXPERIMENTAL SECTION
■
General Information. Substrates, methylene blue, triethyl-
amine (TEA), N,N-diisopropylethylamine (DIPEA),
N,N,N′,N′-tetramethylenediamine (TMEDA), 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU), and DMF were
purchased from commercial suppliers (Sigma-Aldrich, Alfa
Aesar, TCI America, and Fisher) and used with no further
purification unless otherwise noted. The light source, unless
otherwise noted, was two warm white 90 W LEDs, which were
a
Minor products could not be isolated for further characterization.
these results, it is clear that the addition to the more electron-
rich double bond happens before the addition to the terminal
alkene. Note that by changing the reaction conditions, one
could push the selectivity further, depending on whether the
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purchased from LedEngin. Flash column chromatography was
performed using 230−400 mesh silica gel. Preparatory thin
layer chromatography (PTLC) was performed using 1000-μm-
ACKNOWLEDGMENTS
■
This work was supported by the Natural Sciences and
Engineering Research Council of Canada, the Canadian
Foundation for Innovation, and the Canada Research Chairs
program.
1
thick glass baked TLC plates purchased from Silicycle. All H
and proton-decoupled 19F NMR spectra were recorded on a
1
Bruker Avance 400 spectrometer. Chemical shifts (δ) for H
NMR are reported in parts per million from the solvent
resonance as the internal standard (CDCl3: δ 7.26 ppm), and
all proton-decoupled 19F NMR were referenced versus CFCl3
in CDCl3.
REFERENCES
■
(1) Studer, A. Agnew. Chem. Int. Ed. 2012, 51 (36), 8950−8958.
(2) Wang, J.; San
́
chez-Rosello,
́
M.; Acena, J. L.; del Pozo, C.;
̃
Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem. Rev.
2013, 114 (4), 2432−2506.
General Procedure for the Trifluoromethylation of
Electron-Rich Heteroarenes. Heteroarene (0.3 mmol),
methylene blue (2.2 mg, 0.006 mmol), Togni’s Reagent (142
mg, 0.45 mmol), and DMF (3 mL) were added to a 10 mL
Schlenk tube. The reaction mixture was then degassed using
argon for 10−15 min, and TMEDA (90 μL, 0.6 mmol) was
added under argon. The reaction mixture was then irradiated
for 6 h. After irradiation, the mixture was extracted with ether
(×3) and washed with brine (×5), and the ether layer was dried
with MgSO4 before being concentrated with a rotovap. The
crude was purified by either flash column chromatography or
PTLC.
(3) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc.
Rev. 2008, 37 (2), 320−330.
(4) Koike, T.; Akita, M. Top. Catal. 2014, 57, 967−974.
(5) Nagib, D. A.; MacMillan, D. W. C. Nature 2011, 480, 224−228.
(6) Allen, A. E.; MacMillan, D. W. C. J. Am. Chem. Soc. 2010, 132
(14), 4986−4987.
(7) Nagib, D. A.; Scott, M. E.; MacMillan, D. W. C. J. Am. Chem. Soc.
2009, 131 (31), 10875−10877.
(8) Pham, P. V.; Nagib, D. A.; MacMillan, D. W. C. Angew. Chem.
2011, 123 (27), 6243−6246.
(9) Iqbal, N.; Choi, S.; Ko, E.; Cho, E. J. Tetrahedron Lett. 2012, 53
(15), 2005−2008.
(10) Mizuta, S.; Verhoog, S.; Engle, K. M.; Khotavivattana, T.;
General Procedure for the Trifluoromethylation of
Terminal Alkenes and Alkynes. Substrate (0.3 mmol),
methylene blue (2.2 mg, 0.006 mmol), Togni’s Reagent (142
mg, 0.45 mmol), and DMF (3 mL) were added to a 10 mL
Schlenk tube. The reaction mixture was degassed with argon,
and DBU (90 μL, 0.6 mmol) was added under argon. The
reaction mixture was then irradiated for 3 h. After irradiation,
the reaction mixture was diluted with ether (30 mL) and
washed with brine (×5), and the ether layer was dried with
MgSO4 before being concentrated with a rotovap. The crude
was purified by either flash column chromatography or PTLC.
General Procedure for the Triplet Quenching Experi-
ments of Methylene Blue. The triplet-quenching experi-
ments of MB were performed using an excimer laser (308 nm,
10 mJ/pulse) in a LFP-111 laser-flash photolysis (LFP) system
(Luzchem Inc., Ottawa, Canada) and 1 × 1 cm LFP-Luzchem
cuvettes or 1 × 1 cm flow system. Samples of MB were
prepared in solutions of 4:1 MeCN/H2O with a total volume of
3 mL and an absorbance of ∼0.1 at 308 nm. The samples were
degassed with N2 for 30 min prior to use. The substrates used
in the quenching studies were also prepared in solutions of 4:1
MeCN/H2O and degassed for the duration of the experiment.
Because of the overlap of the methylene blue triplet (420
nm) and the semireduced form (430 nm), it was necessary to
use the recovery of ground-state methylene blue (650 nm) to
measure the triplet quenching.
́
O’Duill, M.; Wheelhouse, K.; Rassias, G.; Medebielle, M.; Gouverneur,
V. J. Am. Chem. Soc. 2013, 135 (7), 2505−2508.
(11) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111 (8),
4475−4521.
(12) Parsons, A. T.; Buchwald, S. L. Agnew. Chem. Int. Ed. 2011, 50
(39), 9120−9123.
(13) Wang, X.; Ye, Y.; Zhang, S.; Feng, J.; Xu, Y.; Zhang, Y.; Wang, J.
J. Am. Chem. Soc. 2011, 133 (41), 16410−16413.
(14) Cui, L.; Matusaki, Y.; Tada, N.; Miura, T.; Uno, B.; Itoh, A. Adv.
Synth. Catal. 2013, 355 (11−12), 2203−2207.
(15) Fu, W.; Guo, W.; Zou, G.; Xu, C. J. Fluorine Chem. 2012, 140
(0), 88−94.
(16) Yang, Y.-D.; Iwamoto, K.; Tokunaga, E.; Shibata, N. Chem.
Commun. 2013, 49 (48), 5510−5512.
(17) Wu, X.; Chu, L.; Qing, F.-L. Tetrahedron Lett. 2013, 54 (3),
249−251.
(18) Wilger, D. J.; Gesmundo, N. J.; Nicewicz, D. A. Chem. Sci. 2013,
4 (8), 3160−3165.
(19) Cantillo, D.; de Frutos, O.; Rincon
O. Org. Lett. 2014, 16 (3), 896−899.
́
, J. A.; Mateos, C.; Kappe, C.
(20) Zhang, B.; Studer, A. Org. Lett. 2014, 16 (4), 1216−1219.
(21) Pitre, S. P.; McTiernan, C. D.; Ismaili, H.; Scaiano, J. C. J. Am.
Chem. Soc. 2013, 135 (36), 13286−13289.
(22) Ismaili, H.; Pitre, S. P.; Scaiano, J. C. Catal. Sci. Technol. 2013, 3
(4), 935−937.
(23) Yasu, Y.; Koike, T.; Akita, M. Agnew. Chem. Int. Ed. 2012, 51
(38), 9567−9571.
(24) Yin, B.; Wang, L.; Inagi, S.; Fuchigami, T. Tetrahedron 2010, 66
(34), 6820−6825.
(25) Rao, P. S.; Hayon, E. J. Am. Chem. Soc. 1974, 96 (5), 1287−
ASSOCIATED CONTENT
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1294.
S
* Supporting Information
(26) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of
Photochemistry. Mercel Decker Inc: New York, 1993.
(27) Juillard, J. Pure Appl. Chem. 1977, 49, 885−892.
(28) Iqbal, N.; Choi, S.; Kim, E.; Cho, E. J. J. Org. Chem. 2012, 77
(24), 11383−11387.
(29) Narayanam, J. M. R.; Tucker, J. W.; Stephenson, C. R. J. J. Am.
Chem. Soc. 2009, 131 (25), 8756−8757.
(30) Yamamoto, S.; Fujiyama, Y.; Shiozaki, M.; Sueishi, Y.;
Nishimura, N. J. Phys. Org. Chem. 1995, 8 (12), 805−809.
(31) Chu, L.; Qing, F.-L. J. Am. Chem. Soc. 2011, 134 (2), 1298−
1304.
Details on the synthesis of Togni’s reagent and other substrates,
laser flash photolysis data, quenching plots, and NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
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Corresponding Author
*E-mail: scaiano@photo.chem.uottawa.ca.
Notes
The authors declare no competing financial interest.
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dx.doi.org/10.1021/cs5005823 | ACS Catal. 2014, 4, 2530−2535