Iodine/Visible Light Photocatalysis for Activation of Alkynes for Electrophilic Cyclization Reactions

Article abstract of DOI:10.1021/acscatal.7b00799

Photocatalytic organic synthesis needs photocatalysts to initiate the reactions and to control the reaction paths. Available photocatalytic systems rely on electron transfer or energy transfer between the photoexcited catalysts and the substrates. We expl

Full text of DOI:10.1021/acscatal.7b00799

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Article
Iodine/Visible Light Photocatalysis for Activation
of Alkynes for Electrophilic Cyclization Reactions
Yuliang Liu, Bin Wang, Xiaofeng Qiao, Chen-Ho Tung, and Yifeng Wang
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Iodine/Visible Light Photocatalysis for Activation of Alkynes for
Electrophilic Cyclization Reactions
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Yuliang Liu, Bin Wang, Xiaofeng Qiao, Chen-Ho Tung and Yifeng Wang*
Key Lab of Colloid and Interface Science of the Education Ministry, Department of Chemistry and Chemical Engi-
neering, Shandong University, Ji’Nan 250100, P. R. China
Abstract: Photocatalytic organic synthesis needs photocatalysts to initiate the reactions and to control the reaction paths.
Available photocatalytic systems rely on electron transfer or energy transfer between the photo-excited catalysts and the
substrates. We explore a concept based on the photo-promoted catalyst coupling to the substrate and the photo-triggered
catalyst regeneration by elimination from the catalytic cycle. A catalytic amount of elementary I2 is applied as both a visi-
ble light photocatalyst and a π-Lewis acid, enabling the direct activation of alkyne C≡C bonds for electrophilic cyclization
reactions, one of the most important reactions of alkyne. Visible light is crucial for both the iodocyclization of the propar-
gyl amide and the deiodination of the intermediate. Singlet oxygen is found to play a key role in the regeneration of I2.
This system shows good functional group compatibility for the generation of substituted oxazole aldehydes and indole
aldehydes. Hence this study provides a readily accessible alternative catalytic system for the construction of heterocycle
aldehyde derivatives by sunlight photocatalysis.
Keywords: visible light; photoredox; photocatalysis; alkyne; iodine
1. INTRODUCTION
Recently, visible light photocatalysis has been vastly
explored as a conceptually related valuable method for
organic synthesis.1 This mild, efficient, economic and en-
vironmentally-friendly method has the potential to suc-
ceed in numerous organic transformations that need very
complex procedures or very harsh conditions (e.g., high
temperature, noble metal complexes, strong acids or ba-
ses, multistep, etc), or even were inaccessible, by the tra-
ditional synthetic protocols.1a, b, 2 The key of these photo-
catalysis is a redox-active compound as the photocatalyst,
such as coordination complexes like Ru(bpy)32+, conjugat-
ed organics3 like acridines,4 PDI5 and eosin Y,6 and inor-
Figure 1. The three typical paths of Ru(bpy)32+ photocatalysis
ganic semiconductors7 like CdS and TiO2. The photocata-
and the new photocatalytic model of this work. In the new
lyst is excited by incident photons to generate a charge-
separation state, and the subsequent single electron
transfer (SET) makes the substrate 1e-oxidized or 1e-
reduced which undergoes reaction cascades to give the
the photo-deiodination reaction gives the desired product
desired product (Figure 1A, paths I and II), while the pho-
addition–elimination model, the photocatalyst (i.e., I2) at its
excited state and the substrate react to form an intermediate
(iodination), and at the final stage of the cascade reactions
and the regenerated photocatalyst. The abbreviations are:
tocatalyst is regenerated by another SET with the inter-
Sub = substrate, RQ = reductive quencher, OQ = oxidative
mediates or the co-catalyst.1a, b, 2 Besides, energy transfer
quencher.
from the photo-excited catalyst to the substrate has also
been applied in photosynthesis (path III).8
We anticipate if a photocatalyst possesses a second
function of complexing with the substrate to control the
Comparing with photocatalysis, the transition-metal
reaction pathways – a combination of the advantages of
catalysis has long been applied in laboratory and in indus-
both photocatalysis and transition metal catalysis (Figure
trial applications for organic synthesis.9 Due to the ability
1B), the scope of photocatalysis will be greatly expanded.
of the transition metal complexes of complexing with the
Herein, we report elementary iodine is such a dual-
substrates through oxidative addition, the reaction path-
functional, efficient visible-light photocatalyst. Excited by
ways can be readily fine-tuned.
visible light of the solar spectrum, iodine can directly
couple with the C≡C triple bond, and at the final step of
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the reaction cascade, the photo-deiodination gives the ible light irradiation. However, while there have been few
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desired product and regenerates I2. The syntheses of oxa-
zole aldehydes and indole aldehydes from propargyl am-
ides are chosen as the model reaction.
reports on using I2 in photocatalytic reactions, they were
limited to UV-photocatalysis for selective formation of
aldehydes by oxidation of styrenes,16 benzyl alcohols17 and
amines,18 as well as for the degradation of organic pollu-
tants,19 and therein the photo-generated I∙ radicals were
proposed to be the active species and I2 was regenerated
by the oxidation of I- or I3- by ground state O2.
Since alkynes are a class of fundamental chemicals in
synthesis, the direct activation of C≡C for addition reac-
tions is very important and is one of the most important
applications of C≡C moieties. For this, the π-Lewis acidic
transition-metal complexes such as Au-, Pd- and Cu-
complexes, are widely employed in activation of alkynes
by forming π-complexes intermediates.9b, 10 Considering
activation of C≡C bonds by photocatalysis, it might be
challenging to adopt the SET paths (Figure 1A) to directly
activate C≡C bonds for synthetic purposes, presumably
due to their relatively high redox potentials which can
lead to highly unstable intermediates by SET. For example,
in a recent study, degradation of the C≡C moiety rather
In this work, we demonstrate that under visible light or
sunlight irradiation, a catalytic amount of I2 can realize
the highly efficient activation of alkyne amides for elec-
trophilic cyclization reactions. The mechanism involves a
light-promoted iodocyclization reaction of the propargyl
amide and a light-triggered deiodination of the iodide
intermediate, by which I2 is incorporated in the catalytic
cycling. Singlet oxygen is found to play a key role in the
regeneration of iodine. Hence this study not only provides
a low-cost, highly efficient, mild, eco-friendly and addi-
tive-free catalytic system for construction of oxazole al-
dehyde derivatives and indole aldehyde derivatives, but
also provides a dual-functional visible light photocatalytic
system in which I2 can serve as both a sensitizer/catalyst
and a π-Lewis acid.
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2+
than useful synthesis occurred in the Ru(bpy)3 photoca-
talysis.11 While rare examples proposed 1e-reduction acti-
vation of the C≡C bonds (the radical anion pathways;1b
Figure 1A, path II) for coupling reactions,6 in most studies
only the counterparts of the alkynes were activated.2 For
successful application of sunlight in activation of alkynes,
transition-metal catalysis has been coupled with photoca-
2. RESULTS AND DISCUSSION
12
talysis, such as dual Au/photoredox
,
dual
2.1 Outcome of the I2/visible light photocatalysis in
propargyl amide cyclization. Inspired by the general
Cu/photoredox13, in order to take the advantage of the π-
Lewis acidity of the transition metals.
interests of oxazoles in synthetic chemistry and the pro-
9a, 11, 14, 20
Due to the πꢀLewis acidity, I2 has been widely explored
in catalysis especially in the iodocyclization of alkynes via
a I+ mechanism for the synthesis of heterocyclic com-
pounds.14 The photophysical and photochemical process-
es of I2 have also long been studied. As early as in 1972,
Olmsted III and Karal15 reported that photoexcited I2
could sensitize the formation of singlet oxygen under vis-
pargylic amides
being versatile building precur-
sors to prepare them via an electrophilic 5-exo-dig cycliza-
tion approach,9b, 11, 14, 21 we began our research by choosing
N-(prop-2-yn-1-yl)benzamide (1; Figure 2) as the model
compound, to examine the outcome of yielding 2-(2-
phenyloxazol-5-yl)acetaldehyde (1b) using the I2/visible
light catalytic system.
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no cat, vis-light
I2, dark
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I2, vis-light
I2, sunlight
I2, 450 nm
I2, 395 nm
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I2 (5%), vis-light
I2(10%), vis-light
P25 (2 eq), 395 nm
a
Ru(bpy)32,+ 450 nm
0
20
40
60
80
100
Yield (%)
Figure 2. The products of 1 under various conditions. The other unspecified conditions: 20 mol% catalyst, 0.15 mmol 1, 2.0 mL of
DCE, 1 atm O2, ambient temperature (16 °C), 3-8 h. The yields were obtained by high-performance liquid chromatography
(HPLC). a Data adapted from ref. 11.
The reaction was carried out simply by combining the
substrate (0.15 mmol of 1) and a catalytic amount of io-
dine (e.g., 20 mol%) in a solvent (e.g., 1,2-dichloroethane,
DCE) under 1 atm O2 at ambient temperature (ca. 16 °C),
and visible light drives the reaction in a high efficiency,
e.g., yield of 1b > 90% after 2-hour irradiation (Figure 2).
The light source is a 300 W Xenon lamp equipped with a
400-nm longpass filter (light intensity = 174 mW cm-2) to
simulate the visible region of the solar irradiation. Defin-
ing the quantum efficiency as reacted 1 divided by
amount of photons reaching the reaction cross section,
herein the quantum efficiency of visible light reaches
0.55%. Motivated by the advantages of solar photocataly-
sis,1a we also checked the outcome of reaction 1 irradiated
by outdoor sunlight and, to our delight the solar synthesis
was of high efficiency. The yield of 1b reached 80% after
the 8-hour reaction and the quantum efficiency of sun-
light is as high as 2.4%. If the same reaction was carried
out using a 450 ± 10 nm blue LED, the yield of 1b was also
as high as 88% with a quantum efficiency of 0.5%. This
outcome approaches that using 395 ± 10 nm LED. Howev-
er, without light irradiation, for the same reaction (with
20 mol% I2) the conversion of 1 was as low as 10%, while
no 1b was yielded; instead, ca. 10% of 5-(iodomethylene)-
2-phenyl-4,5-dihydrooxazole (1a) was formed. Control
experiments also showed that, without I2, 1 remained in-
tact upon light irradiation. This is consistent with the
electronic absorption spectra (Figure 3) which show both
1 and 1a have negligible absorbance at λ > 350 nm, and I2
is the only visible-light absorber in this catalytic system.
Also, because O2 is the only source of carbonyl-O of 1b,
activation of O2 must be involved in the photocatalytic
reaction. Therefore, I2 is an efficient visible-light photo-
catalyst and it effectively activates O2 for oxygenation
reactions; a highly efficient solar photocatalytic system
has been established for activation of the alkyne for elec-
trophilic additions.
2.0
1a
1
1.5
I2
1.0
0.5
0.0
200
300
400
500
600
700
800
Wavelength (nm)
Figure 3. The UV-vis spectra of the DCE solutions of I2 (7.6
mM), 1 (0.28 M) and 1a (1.16 M).
Products of 1 by photocatalysis using TiO2/UV and
Ru(bpy)32+/visible light, the most popular heterogeneous
and homogeneous photocatalytic systems, respectively,
are compared with the current I2/visible light system.
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TiO2 and Ru(bpy)32+ are known to activate the substrates
the dark reaction was also studied (Figure 4B). The color
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by electron transfer processes (Figure 1). However, under
395 nm LED irradiation for TiO2, or under 450 nm irradia-
tion for Ru(bpy)3Cl2, 1 was mainly degraded to an alde-
hyde (1c), instead of yielding any cyclization product
(Figure 2). This might suggest that ET processes be rela-
tively challenging for activation of C≡C bonds for synthet-
ic purposes. Wang et al. recently used eosin Y/visible light
for activation of alkynes for S-nucleophiles addition for
the synthesis of α-vinyl sulfones.6 The authors proposed
that the reaction was initiated by 1e-reduction of the C≡C
bond by the photo-excited dye.6 To our knowledge, de-
spite the great dependency on the additives in such catal-
ysis, this is one of the very rare examples of using the ET
mechanism to activate the C≡C bonds in solar synthesis.
of the mixture reduced greatly after 20 min, indicating the
-
consumption of I2 and formation of I3 which was con-
firmed by UV-vis spectra. The dark reaction gave 1a as the
major product rather than any amount of the oxazole
aldehyde 1b. The yield of 1a reached a plateau of ca. 17%,
which is ca. half of the catalyst loading (note that 30
mol% of I2 was used in this case).
A 100
9
1b
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Due to its importance, reaction 1 has been studied time
catalysis,22
system,11
the
the
1a
and
again
using
Au(I)
20
PPh3AuNTf2/Fe(acac)2/peroxide
Pd(II)/Cu(II)/O2 system,23 the Hg(II) system,24 the
Hg(II)/Ce4+ system,24 and the hypervalent iodine (NIS)/O2
system,25 respectively, under relative harsh conditions.
Comparing to these catalytic systems, while the current
yield is comparable or even better, the advantage of the
I2/visible light photocatalysis is obvious, for example, it
adopts a cheap, readily available and eco-friendly photo-
catalyst, it works under very mild reaction conditions, it
uses costless sunlight and dioxygen as the reagents, and
moreover any additive is not necessary.
0
0
20
40
60
80
Time (min)
B
100
80
60
40
20
0
1
2.2 The photocatalytic tandem reaction. We noticed
that when the amount of I2 was less than 20 mol%, the
yield of 1b increased with the catalyst loading (Figure 2),
and meanwhile the purple color of the I2/DCE solution
diminished quickly in the beginning of the photocatalytic
reaction. With more than 20 mol% I2, the solution color
changed from purple to red but recovered at the reaction
late stage. The UV-vis spectrum of the discoloring solu-
tion (i.e., early stages of the reaction) indicates I3- was
formed (see Figure S2).
1a
1b
0
20
40
60
80
Time (min)
Figure 4. Reaction kinetic profiles of (A) the photocatalytic
and (B) the dark reactions. Conditions: 20 mol% I2 for A and
30 mol% I2 for B, O2, DCE, 395 nm LED, 16 °C.
Using HPLC, we found the photocatalytic reaction 1 in-
volves only one intermediate, i.e., an iodide complex 1a.
No other stable intermediate was identified by GC-MS
analyses, either. When 1a was subjected to the same reac-
tion conditions, it resulted solely in 1b in over 95% yield.
2.3 The photo-promoted iodocyclization reaction
of the propargyl amide. As mentioned above, in the
early stage of the photocatalytic reaction (e.g., within the
first 6 min), accumulation of the intermediate 1a domi-
nated the reaction (eq 3), no 1b was formed, and mean-
while I2 was converted to 1a and I3-. This is also true for
the same reaction carried out in the dark (Figure 4).
Hence, the absorbance change of I2 can be used as a quick
solution to track the reaction, and thereby the effect of
visible light in the 5-exo-dig iodocyclization of 1a (eq 3)
can be quantitatively evaluated. For this, a DCE solution
containing the substrate was carefully agitated by O2
bubbles (to ensure mixing and to maintain 1 atm O2), and
to this solution was quickly added the 20 mol% of I2 (in
DCE) to initiate the photocatalytic reaction or the dark
reaction. The kinetics was then monitored by UV-vis
spectroscopy at 500 nm at which I2 is the only light ab-
sorber of the reaction mixture. As shown in Figure 5, I2
was quickly converted during both the photocatalytic
reaction and the dark reaction. However, the data shows
-
UV-vis spectroscopic study ruled out formation of I3 in
this step (Figure S3). Hence, reaction 1 involves the tan-
dem iodocyclization of 1 followed by the deiodination of
1a (eq 2).
Detailed kinetic profile of the tandem reaction (eq 2)
was then obtained (Figure 4A). It was found out that as
the photocatalytic reaction proceeded, the key intermedi-
ate 1a was accumulated within the first 25 min and during
this period 1b was hardly formed. The highest yield of 1a
reached nearly 30%, which is 1.5 times of the amount of
initially added I2. Afterwards, 1a was gradually consumed
with the production of 1b. For comparison, the kinetics of
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0
that the photocatalytic reaction is faster than the dark
reaction, indicating that visible light promotes the iodo-
1
2
3
4
5
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cyclization reaction of 1. In addition, if the photocatalytic
reaction was carried out under Ar atmosphere, then the
conversion of I2 is faster than that under O2. This phe-
nomenon is consistent with the role of O2 in regeneration
of I2 and will be discussed later.
a
b
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Time (min)
Figure 6. Formation of I2 during the reaction of 1a: (a) 20
mol% I2, light; (b) no I2, light; (c) no I2, dark. Other condi-
tions: O2, DCE, 395 nm LED, 16 °C.
10
Besides, to verify the role of light as a reagent in the re-
action, the 1a/DCE solution was settled under 1 atm O2 at
ambient or elevated (80 °C) temperatures, and by ambi-
ent light irradiation or kept in the dark. It was found out
that conversion of 1a was nearly 0 in the dark reaction at
ambient temperature. Hu et al.25 recently reported that
the oxidative deiodination of 1a to give 1b can be achieved
O2, dark
O2, light
5
Ar, light
0
1
2
3
4
5
6
Time (min)
at 80 °C. Flynn et al.21c, also reported that the de-
d
iodination of an analogous vinyl iodide can be accom-
plished at elevated temperature. Consistent with their
reports, at 80 °C under ambient light irradiation, 1a was
nearly quantitatively converted to 1b (95% HPLC yield)
after 24 h reaction. However, when the same reaction was
performed in the dark, the conversion was low and less
than 15% 1b was yielded. We further examined the dark
reaction of eq 1 in which a stoichiometric amount of I2
was present. For this, 1 and 110 mol% I2 was reacted at
ambient temperature for 1 h, and then the mixture was
maintained 80 °C for 10 h. The substrate conversion
reached completion, however, this dark, thermal reaction
yielded mainly the aldehyde 1c (55% yield; the degrada-
tion product) and a little amount of the desired cycliza-
tion product 1b (6% yield). In all, the above control exper-
iments clearly indicate the essential role of light in the
formation of 1b.
Figure 5. Conversion of I2 under O2 (■) or under Ar (▲) at-
mosphere during irradiation, or under O2 atmosphere in the
dark (●). Conditions: 20 mol% I2, DCE, 395 nm LED, 16 °C.
2.4 The photocatalytic deiodination of the vinyl io-
dide. We now show the oxidative deiodination of the
vinyl iodide is a photocatalytic reaction with I2 as the pho-
tocatalyst (eq 4).
First, to verify the function of I2, we quantified the reac-
tion kinetics under light irradiation with or without add-
ed 20 mol% I2. Release of I2 from 1a was eyed as the solu-
tion turned purple. The UV-vis absorbance change of the
solution at 500 nm (Figure 6) shows that with or without
added I2, 1a could be nearly quantitatively converted to
1b and 0.5 eq of I2. However, without added I2, an obvious
induction period existed, during which the reaction solu-
tion gradually turned purple (accumulation of I2), show-
ing this is an autocatalytic reaction. With added 20 mol%
I2, the induction period disappeared, and hence the pho-
toexcited I2 must serve as the catalyst in this reaction (eq
4).
For the photocatalytic reaction with 20 mol% added I2,
the absorbance of I2 is thousands of times larger than the
concomitant species, i.e., 1a and 1b. Hence the autocata-
lytic reaction of 1a should be minor when I2 is present.
Therefore, in both the tandem reaction (eq 1) and the de-
iodination reaction (eq 4) with added I2, I2 is the actual
light absorber and the photocatalyst.
2.5 The engagement of singlet oxygen in the iodo-
cyclization and the deiodination reactions. It has
been established that visible light (390 – 700 nm) is suffi-
cient to excite an I2 molecule to its excited triplet state
(3I2*; eq 5),26 which can sensitize the ground-state dioxy-
gen to produce singlet oxygen (eq 6),15, 26 and can also
split into 2 equivalents of I∙ radicals (eq 7).26
1I2 + hν → 3I2*
(5)
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1
3I2* + 3O2 → I2 + 1O2
3I2* → I∙ + I∙
(6)
reactions were hardly affected (entry 10), and hence the
involvement of O2•− can be ruled out.
1
(7)
2
3
4
5
6
7
8
9
3
We consider that O2 is not directly responsible for the
oxidative regeneration of I2 from I3-. Otherwise, in the
dark reaction of Figure 4B, more iodide complex 1a
should have been produced; however, therein the low
atomic efficiency of I2 actually indicates the inability of
the dark reaction in regeneration of I2 from I3-, due to the
lack of an oxidizing reagent like 1O2. Further, the 1O2 scav-
Formation of singlet oxygen in the I2/visible light pho-
tocatalytic synthesis of 1b was investigated by the peroxi-
dation of α-terpinene.27 For this, reaction 1 and reaction 4
were independently carried out with added α-terpinene (1
equiv). The expected peroxidation product of α-terpinene
1
by O2, namely, ascaridole, was indeed identified using
GC-MS (Figure S4).27a
3
engers (entries 4-9) should not be able to quench O2-
To determine whether singlet oxygen plays a key role in
the photocatalytic reaction outcome and in the regenera-
tion of I2, a set of control experiments were carried out
(Table 1). Under the standard conditions, with only 20
mol% I2, both the conversion of 1 and the yield of 1b are
near to 100%, while the highest accumulated yield of 1a
could reach 1.5 times of the amount of the initially added
I2. However, without O2, the light-driven reaction was
greatly suppressed and became a stoichiometric reaction
(entries 2–3); therein light perhaps can only affect the
reaction rate, instead of contributing to the reaction out-
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involved reactions. Importantly, comparing the redox
potentials, because E°(I2/I-) = +0.536 V is more positive
than that of the 3O2/3O2- pair (-0.16 V), direct oxidation of
I- to I2 by ground state 3O2 is thermodynamically unfavor-
able by an abiotic, thermal, one-electron transfer
1
-
process.28 By contrast, the O2/1O2 pair has a positive
enough potential of +0.83 V for the oxidative regeneration
of I2.
2.6 Mechanism for the photocatalytic reaction.
With the above evidences and discussions, a mechanism
for the I2/visible light photocatalysis is proposed (Scheme
1). In this mechanism, I2 serves as the photo-absorber, the
singlet oxygen sensitizer and one of the reactants of the
iodocyclization reaction. The π-Lewis acidity of the pho-
to-excited iodine makes it readily activate the C≡C bonds
of 1 for the nucleophilic addition by the amide moiety.
Singlet oxygen plays the key role in the regeneration of I2
-
come. In both cases, I3 was detected. Hence, to enable
iodine as a catalyst in the light-driven reaction, oxygen is
essential in the regeneration of I2.
Table 1. Modification of experimental parameters abcd
entry change of
conditions
1 → 1a + 1b, 2h
conv / 1a /1b, %
100 / 0 / 92
15 / 8 / 0
1a → 1b, 0.5 h
conv / 1b, %
100 / 95
n.r.
-
by the oxidation of I3 and by the oxidative deiodination of
1a.
1
2
3
no change
dark
Ar
10 / 9 / 0
n.r.
4
5
6
7
8
9
10
carotene, light 13 / 8 / 0
carotene, dark 8 / 7 / 0
n.r.
n.r.
n.r.
n.r.
n.r.
n.r.
100 / 90
TEMPO, light
TEMPO, dark
TMP, light
30 / 11 / 0
25 /10 / 0
15 / 8 / 0
TMP, dark
SOD, light
17 / 6 / 0
100 / 0 / 87
a
Other unspecified conditions: 0.15 mmol substrate, 20
mol% I2, 2 mL DCE, 1 atm O2, 16 °C, 395 nm LED. b Two
equivalents of the scavengers were added. HPLC yields.
c
d
Scheme 1. The proposed mechanism
n.r. is short for “no reaction”.
The above mechanism explains why the highest accu-
mulated yield of 1a in the photocatalyzed reaction (of
Figure 4A) exceeds the amount of initially added I2. This
The effects of various scavengers were then investigat-
1
ed, including three O2 scavengers like carotene, 2,2,6,6-
tetramethyl-1-piperidinooxy
(TEMPO),
2,2,6,6-
-
•−
is due to the oxidation of I3 by singlet oxygen, which en-
tetramethyl-4-piperidone (TMP) and an O2 quencher,
superoxide dismutase (SOD). It was found out that with
hances the atomic-efficiency of I2 in the iodocyclization
reaction (the first step of the cascade reaction). Contribu-
1
each of the three O2 scavengers added (entries 4-9), con-
1
tion of dark reaction (by I2) in the formation of 1a is not
version of 1 to 1a under light irradiation was greatly sup-
pressed, and meanwhile the deiodination of 1a was com-
pletely quenched. Hence, contribution of photocatalysis
was indeed quenched. Therefore, singlet oxygen must be
an important active oxygen species in the photocatalytic
excluded, but regeneration of I2 by oxygen can be trig-
gered only by light irradiation.
2.7 Scope of the I2/visible light photocatalysis in the
electrophilic cyclization of alkyne amides. With the
success in highly efficient synthesis of 1b using the
I2/visible light photocatalysis and the mechanism revealed,
a variety of substituted propargyl amides were then inves-
tigated in this new photocatalytic system to examine the
substrate compatibility (Table 2). The substrates with
-
reaction. Further, it serves to oxidize I3 to regenerate I2 in
the iodocyclization reaction (eq 3) and to initiate the de-
iodination of 1a (eq 4). Consistent with this, when SOD
was adopted to selectively quench O2•−, the photocatalytic
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EWGs and EDGs at the benzene ring of 1 all furnished the
corresponding oxazole aldehydes in good to excellent
1
2
3
4
5
6
7
yields (1b-9b). Heteroaromatic substrates (10b, 11b) and
vinyl substituted propargyl amides (12b) also worked well.
The aliphatic substituted propargyl amides gave accepta-
ble yields (13b, 14b). For internal alkynes, the desired
product was poor (15b), making this simple strategy im-
practical.
8
9
Table 2. Reaction scope for syntheses of oxazole alde-
hydes abc
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
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a Conditions: 0.15 mmol substrate, 20 mol% I2, 2 mL DCE, 1
atm O2, 16 °C, 395 nm LED. b Isolated yields. c 4 h.
2.8 Gram scale reaction. To highlight the efficiency of
the I2/visible light system for practical application in the
activation of alkynes for the 5-exo-dig cyclization reac-
tions, we conducted the cyclization of 1 and 22 on gram
scale on a laboratory windowsill using sunlight as the only
source of irradiation. Interestingly, the outcome is even
better (Scheme 2) than the smaller scale reaction. With
1.0 g (6.4 mmol) of 1 the reaction achieved completion
after only ca. 20 h sunlight irradiation, providing an 86%
yield of 1b. The yield of 22b reached 62%, almost the same
as the smaller scale reaction using 395 nm LED irradiation
(Table 3).
a Conditions: 0.15 mmol substrate, 20 mol% I2, 2 mL DCE, 1
atm O2, 16 °C, visible light. b Isolated yields. c 4 h.
Scheme 2. Gram-scale synthesis of 1b and 22b using
I2/sunlight photocatalysis
In order to test the potential of the I2/visible light sys-
tem in more challenging reactions, the 5-exo-dig cycliza-
tion of 2-tosylaminophenylprop-1-yn-3-ols for the prepa-
ration of substituted indole aldehyde was then investigat-
ed (eq 8).29 Previous reports have demonstrated that such
transformation is very challenging for Au catalysis for
which transition-metal co-catalysts, Lewis acids, oxidants
and elevated temperature are usually essential for the
success.11, 29b For example, efficient syntheses of substitut-
ed indoles catalyzed by AuCl was performed in the pres-
ence of AgOTf, hexamethylphosphoramide and CaSO4
under reflux conditions.29b Efficient syntheses of substi-
tuted indole aldehydes were realized by using the dit-
BuXphosAu(CH3CN)SbF6/FeCl2 dual catalytic system.11
However, to our delight, the I2/visible light photocatalytic
system, which is carried out without any additive and
under very mild conditions, proves to be a practical pro-
tocol for this transformation (Table 3).
3. CONCLUSION
In conclusion, linked by I2/visible light activation of C≡
C triple bond followed by nucleophilic addition by elec-
tron-donating amide groups, we have exhibited I2 is an
efficient visible light photocatalyst for synthesis of oxa-
zole aldehyde and indole aldehyde derivatives. Light is
crucial for triggering these catalytic transformations un-
der mild conditions, using a catalytic amount of I2 and
without any additives. Elementary I2 serves as both a visi-
ble light photocatalyst and a π-Lewis acid during the pho-
tocatalysis. Singlet oxygen plays a pivotal role in I2 regen-
eration.
We anticipate that the novel photocatalytic path (Fig-
ure 1B) and the dual functions of I2 in visible light photo-
catalysis, will enable the simple, economic and eco-
friendly approach of a variety of syntheses which are chal-
lenging for other catalytic systems, especially those rele-
vant to C≡C activations which are currently being per-
formed mainly with transition metals under relatively
harsh conditions.
Table 3. Syntheses of indole aldehydes abc
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11. Peng, H.; Akhmedov, N. G.; Liang, Y.-F.; Jiao, N.; Shi, X. J.
Am. Chem. Soc. 2015, 137, 8912-8915.
12. Hopkinson, M. N.; Tlahuext-Aca, A.; Glorius, F. Acc.
Chem. Res. 2016, 49, 2261-2272.
ASSOCIATED CONTENT
AUTHOR INFORMATION
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2017, 19, 1016-1019.
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16. Itoh, A.; Kodama, T.; Masaki, Y.; Inagaki, S. Synlett. 2002,
3, 522-524.
Corresponding Author
*E-mail: yifeng@sdu.edu.cn
Notes
The authors declare no competing financial interest.
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Supporting Information
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Lett. 2006, 47, 8953-8957. (b) Itoh, A.; Kodama, T.; Masaki, Y.
Chem. Lett. 2001, 686-687.
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The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/xxxxxxxxxxx.
Detailed experimental procedures, supplementary data,
and characterization data of all the compounds (PDF)
19. Hu, M.; Wang, Y.; Xiong, Z.; Bi, D.; Zhang, Y.; Xu, Y.
Environ. Sci. Technol. 2012, 46, 9005-9011.
ACKNOWLEDGEMENTS
20. (a) Wang, B.; Chen, Y.; Zhou, L.; Wang, J.; Tung, C.-H.;
Xu, Z. J. Org. Chem. 2015, 80, 12718-12724. (b) Hashmi, A. S.
K.; Schuster, A. M.; Schmuck, M.; Rominger, F. Eur. J. Org.
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S.; Schuster, A.; Hengst, T.; Schetter, S.; Littmann, A.;
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Chem. Lett. 2013, 24, 957-961.
We thank the NSFC (Grants 21401117 and 21473104), the
Natural Science Foundation of Shandong Province (Grant
ZR2014BQ003), and Shandong University (Grant
104.205.2.5) for the financial support.
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the high resolution version of Figure 1
1736x1036mm (72 x 72 DPI)
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