Photooxidative cleavage of aromatic alkenes into aldehydes using catalytic iodine and molecular oxygen under visible light irradiation

Article abstract of DOI:10.1055/s-0033-1340735

We report a method for the photooxidative cleavage of aromatic alkenes to give aldehydes using molecular oxygen as the terminal oxidant, visible light, a catalytic amount of iodine and trifluoroacetic acid.

Full text of DOI:10.1055/s-0033-1340735

8
84▌
LETTER
lPettherotooxidative Cleavage of Aromatic Alkenes into Aldehydes Using Catalytic
Iodine and Molecular Oxygen under Visible Light Irradiation
Photooxidative Cleavage of Alkenes
a
a
a
a
b
a
Akitoshi Fujiya, Atsumasa Kariya, Tomoya Nobuta, Norihiro Tada, Tsuyoshi Miura, Akichika Itoh*
a
Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
Fax +81(58)2308108; E-mail: itoha@gifu-pu.ac.jp
b
Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received: 24.09.2013; Accepted after revision: 13.01.2014
and harmful UV light. In addition, they cannot be per-
formed under an air atmosphere and the substituent scope
of the substrates has not been investigated.
Abstract: We report a method for the photooxidative cleavage of
aromatic alkenes to give aldehydes using molecular oxygen as the
terminal oxidant, visible light, a catalytic amount of iodine and tri-
fluoroacetic acid.
We have developed various aerobic photooxidation pro-
cesses under an oxygen atmosphere using visible light ir-
Key words: alkenes, aerobic, photooxidation, iodine, aldehydes
1
5
radiation and inexpensive iodine or bromine sources as
catalysts.16 We previously reported the synthesis of the
corresponding carboxylic acids through aerobic photoox-
idative cleavage of styrenes using molecular iodine–
FSM-1617 or carbon tetrabromide (CBr4). However,
these methods also have some limitations, such as the use
of harmful UV light and molecular oxygen rather than air.
Furthermore, under these reaction conditions, carboxylic
acids were obtained, and only low yields of aldehydes
could be recovered. In continuation of our efforts to de-
velop an efficient protocol for the oxidative cleavage of
alkenes, we report herein the molecular iodine catalyzed
photooxidative cleavage of aromatic alkenes in the pres-
ence of air and visible light irradiation to give the corre-
sponding aldehydes (Scheme 1).
The carbon–carbon double bond is a key functional group
for transformation in organic synthesis, and various reac-
tions starting from alkenes have been developed. Among
them, cleavage of alkenes to give carbonyl compounds is
18
1
one of the most important examples. Ozonolysis is prob-
ably the best known method for the cleavage of alkenes.2
However, its utility is often limited by safety concerns;
there have been some reports of serious accidents due to
1
9
3
explosions. Alternatively, transition metal catalysts such
as osmium (Os), ruthenium (Ru), tungsten (W), iron (Fe),
vanadium (V), and palladium (Pd), have been used to
4
cleave carbon–carbon double bonds. Since these cata-
lysts have several drawbacks, such as high cost and detri-
mental environmental impact, the development of less
expensive and more environmentally benign methods are
very important. However, catalytic metal-free reactions,
air, hν (Vis)
O
I2 (0.1 equiv)
TFA (0.2 equiv)
R
5
H
such as those using a triarylamine electrocatalyst, tert-
2
R
MeOH–EtOAc, 20 h
6
R
butyl nitrite/oxygen/compressed carbon dioxide, and
iodomesitylene/m-chloroperoxybenzoic acid (MCPBA),
are limited.
7
Scheme 1 Photooxidative cleavage of aromatic alkenes into alde-
hydes
Light is an important factor in many reactions because it
leaves no residue, has neither shape nor weight, and is an
important component in the examination of environmen-
Table 1 shows the results of our investigation of the reac-
tion conditions for the photooxidative cleavage reaction.
The reaction conditions were examined with trans-4,4′-
di-tert-butylstilbene (1a) as a test substrate in the presence
of iodine sources and additives under air (open), with irra-
diation using four 22 W fluorescent lamps for 20 hours. In
a preliminary experiment using methanol as the solvent,
aldehyde 2a (2%) and the corresponding dimethylacetal
(63%) were obtained without an acidic work-up. Conse-
quently, work-up using aqueous hydrochloric acid (2 M)
extraction was employed, which resulted in the formation
of aldehyde 2a and its corresponding methyl ester.
Among the iodine sources examined, molecular iodine
gave good result (Table 1, entries 1–4). Of the solvents
employed, methanol gave a low yield of 2a because al-
kene 1a was insoluble in this solvent (Table 1, entry 6).
Thus, the combination of methanol and ethyl acetate,
which dissolved substrate 1a, was found to afford the de-
8
tally friendly processes. In addition, due to the increasing
demand for more environmentally benign syntheses, mo-
lecular oxygen, which is inexpensive and has greater atom
efficiency than other oxidants, has received considerable
9
attention as the ultimate oxidant. Thus, an aerobic photo-
oxidative carbon–carbon bond cleavage reaction is attrac-
tive, and various reactions which use stoichiometric
1
0
amounts of dimethoxybenzene, catalytic amounts of
,10-dicyanoanthracene (DCA),1 5,10,15-triphenyl-20-
1
9
(
1
2
4-hydroxyphenyl)-21H,23H-porphyrin (TPP-OH), and
1
3
14
metal catalysts (Pt, Mn ), have been reported. However,
these reactions require stoichiometric amounts of reagents
SYNLETT 2014, 25, 0884–0888
Advanced online publication: 10.02.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340735; Art ID: ST-2013-U0905-L
Georg Thieme Verlag Stuttgart · New York
©

LETTER
Photooxidative Cleavage of Alkenes
885
sired product most efficiently (Table 1, entries 4, 6 and 7). Table 2 presents the scope and limitations of the photoox-
Subsequently, a series of additives were evaluated, and idative cleavage reactions under the optimized reaction
trifluoroacetic acid (TFA) (0.2 equiv) provided the best conditions described above.20 Electron-rich trans-stil-
result (Table 1, entries 4 and 8–10). It was noted that io- benes 1a–1g, which have t-butyl, ethyl, and methyl
dine sources, trifluoroacetic acid, molecular oxygen, and groups on the benzene ring, and trans-stilbene (1h) gave
visible light irradiation were necessary, otherwise unre- good to high yields of the corresponding aldehydes (Table
acted substrates were recovered (Table 1, entries 5 and 2, entries 1–8). It should be noted that the presence of or-
1
1–13). When the reaction was carried out under an oxy- tho-methyl groups was tolerated in this reaction (Table 2,
gen atmosphere, over-oxidation of the aldehyde proceed- entries 5–7). However, electron-rich trans-stilbene 1i
ed to give methyl 4-tert-butylbenzoate (12%) and 4-tert- bearing methoxy groups on the benzene rings, electron-
butylbenzoic acid (32%) (Table 1, entry 14).
poor trans-stilbene 1j with bromines on the aromatic
rings, 4-tert-butylstyrene (1k), and cyclohexene (1l) were
poor substrates in this reaction (Table 2, entries 9–12).
Table 1 Optimization of the Reaction Conditionsa
t-Bu air, hν (Vis)
iodine source
additive
We performed control experiments in order to determine
the reaction mechanism. 3,5-Di-tert-butyl-4-hydroxytolu-
ene (BHT), which is a radical inhibitor, completely sup-
pressed the reaction. This result suggests that the
photooxidation proceeds via a radical mechanism
O
H
solvent, 20 h
t-Bu
t-Bu
1a
2a
(
Scheme 2, equation 1). On the other hand, when vicinal-
Entry I source Solvent
Additive
(equiv)
Yield
(%)
2
diol 3 was used as a substrate, only trace amounts of benz-
aldehyde were obtained and the majority of 3 was recov-
ered (Scheme 2, equation 2).
b
(
equiv)
(mL)
1
2
3
Cl (0.1) MeOH–EtOAc (1:2) TFA (0.2)
trace
50
4
NaI (0.1) MeOH–EtOAc (1:2)
TFA (0.2)
air, hν (Vis)
I2 (0.1 equiv)
TFA (0.2 equiv)
BHT (1 equiv)
CaI (0.1) MeOH–EtOAc (1:2) TFA (0.2)
76
2
O
4c I2 (0.1)
MeOH–EtOAc (1:2) TFA (0.2)
MeOH–EtOAc (1:2) TFA (0.2)
84 (84)
trace
trace
29
H
H
+
+
1h (83%) (1)
MeOH (3 mL), 20 h
5
6
7
8
9
0
1
–
1
h
2h (0%)
I2 (0.1)
MeOH (3)
EtOAc (3)
TFA (0.2)
TFA (0.2)
air, hν (Vis)
I2 (0.1 equiv)
TFA (0.2 equiv)
I2 (0.1)
OH
O
I2 (0.1)
MeOH–EtOAc (1:2) TFA (0.1)
36
3 (92%) (2)
MeOH (3 mL), 20 h
OH
I2 (0.1)
MeOH–EtOAc (1:2)
MeOH–EtOAc (1:2)
MeOH–EtOAc (1:2)
PTSA·H O (0.2) 65
2
3
2h (trace)
1
1
1
1
I2 (0.1)
I2 (0.1)
AcOH (0.2)
–
8
0
Scheme 2 A study of the reaction mechanism
2d I2 (0.1)
3e I2 (0.1)
MeOH–EtOAc (1:2) TFA (0.2)
MeOH–EtOAc (1:2) TFA (0.2)
MeOH–EtOAc (1:2) TFA (0.2)
0
Scheme 3 shows a plausible mechanism for this oxidative
cleavage reaction, which was proposed from the results
presented above. Initially, the alkene is iodo-methoxylat-
ed in the presence of trifluoroacetic acid to give 4, and
subsequent homolytic cleavage of the C–I bond occurs
under visible light irradiation to produce the benzyl radi-
cal species 5. In contrast, when an aliphatic alkene was
used as the substrate, the C–I bond probably cannot be
cleaved to form an unstable alkyl radical. Intermediate 5
traps molecular oxygen from air to afford hydroperoxide
0
1 f
4
36
I2 (0.1)
a
A solution of trans-4,4′-di-tert-butylstilbene (1a) (0.15 mmol), io-
dine source and additive in a dry solvent was stirred in a Pyrex test-
tube under air (open), and externally irradiated with four 22 W fluo-
rescent lamps for 20 h. Aqueous Na S O was added to the mixture,
2
2
3
which was extracted with EtOAc. The organic layer was washed with
brine and aqueous HCl (2 M).
b
1
Yields determined by H NMR spectroscopy. Yield of isolated prod-
7
via peroxy radical 6. Next, C–C bond cleavage occurs in
uct is in parenthesis. The product yields were calculated based on 0.3
mmol of corresponding aldehydes.
+
21,22
the presence of H to afford aldehyde 2 or acetal 10.
c
Methyl 4-tert-butylbenzoate (7%) was obtained as a by-product.
The reaction was carried out under N2.
The reaction was carried out in the dark.
The reaction was carried out under O . Methyl 4-tert-butylbenzoate
Acetal 10 is relatively stable under these reaction condi-
tions with iodine as the catalyst, in contrast to reactions
with bromine sources. Finally, acetal 10 is transformed
into aldehyde 2 during the acidic work-up with aqueous
hydrochloric acid. Furthermore, in situ generated hydro-
gen iodide is reoxidized to iodine under aerobic photoox-
idation conditions.
d
e
f
2
(
12%) and 4-tert-butylbenzoic acid (32%) were obtained as by-prod-
ucts.
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 884–888

8
86
A. Fujiya et al.
LETTER
Table 2 Scope and Limitationsa
air, hν (Vis)
I2 (0.1 equiv), TFA (0.2 equiv)
Ar
ArCHO
Ar
solvent
1
2
20 h
Entry
Substrate
Solvent (mL)
Yield (%)b
t-Bu
1
MeOH–EtOAc (1:2)
MeOH–EtOAc (2:1)
84
t-Bu
1
a
Et
2
79
Et
1
b
c
d
e
f
3c
MeOH–EtOAc (2:1)
79
1
1
1
1
4
MeOH (3)
30 (83)
5c
MeOH (3)
88
6
MeOH–EtOAc (1.5:1.5)
71
7
8
MeOH–EtOAc (4:6)
63
1
1
g
MeOH (3)
30 (67)
h
Synlett 2014, 25, 884–888
© Georg Thieme Verlag Stuttgart · New York

LETTER
Photooxidative Cleavage of Alkenes
887
Table 2 Scope and Limitationsa (continued)
air, hν (Vis)
I2 (0.1 equiv), TFA (0.2 equiv)
Ar
ArCHO
Ar
solvent
1
2
20 h
Entry
Substrate
Solvent (mL)
Yield (%)b
OMe
9
MeOH–EtOAc (1:2)
MeOH–EtOAc (1:2)
(12)
MeO
1
i
Br
1
1
0
0
Br
1
j
1
2
MeOH–EtOAc (1:2)
MeOH–EtOAc (1:2)
(2)
(0)
t-Bu
1
k
1
1
l
a
A solution of substrate 1 (0.15 mmol), I (0.1 equiv) and TFA (0.2 equiv) in a dry solvent was stirred in a Pyrex test-tube under air (open), and
2
externally irradiated with four 22 W fluorescent lamps for 20 h. Aqueous Na S O was added and the mixture extracted with EtOAc. The or-
2
2
3
ganic layer was washed with brine and aqueous HCl (2 M).
b
1
Yields determined by H NMR spectroscopy. Yields of isolated products are in parentheses. The product yields were calculated based on 0.3
mmol of the corresponding aldehydes.
c
I2 (0.05 equiv) was used.
H+
I2
MeOH
visible light from general purpose fluorescent lamps. The
application of this photooxidation to other reactions is
now in progress in our laboratory.
I
O2
hν
Ar
Ar
Ar
OMe
Ar
OMe
Ar
Ar
Ar
Ar
Ar
HI
HI
1
4
5
Acknowledgment
+
O
OH
OH2
This work was supported by a Grant-in-Aid for Young Scientists
O
O
H+
O
H+
(
B) (No. 24790015) from the Japan Society for the Promotion of
Ar
Ar
OMe
Ar
Ar
Science (JSPS).
H2O
OMe
OMe
6
7
8
H+
MeOH
References and Notes
O
+OMe
OMe
O
workup
aq HCl
+
(1) Comprehensive Organic Transformations: A Guide to
Functional Group Preparations; Larock, R. C., Ed.; Wiley-
VCH: New York, 1999, 2nd ed., 1213.
H
Ar
H
Ar
OMe
Ar
H
2
9
10
2
(
2) Bailey, P. S. Chem. Rev. 1958, 58, 925.
O2, hν
(
3) (a) Dorofeev, S. B.; Eletskii, A. V.; Smirnov, B. M. Dokl.
Akad. Nauk SSSR 1981, 257, 592. (b) Koike, K.; Inoue, G.;
Fukuda, T. J. Chem. Eng. Jpn. 1999, 32, 295. (c) Ogle, R. A.;
Schumacher, J. L. Process Saf. Prog. 1998, 17, 127.
HI
I2
Scheme 3 A plausible reaction mechanism
(
4) For recent examples, see: (a) Travis, B. R.; Narayan, R. S.;
Borhan, B. J. Am. Chem. Soc. 2002, 124, 3824. (b) Kumar,
A. V.; Prakash, R. V.; Sridhar, R.; Srinivas, B.; Rama, R. K.
Synlett 2009, 739. (c) Kogan, V.; Quintal, M. M.; Neumann,
R. Org. Lett. 2005, 7, 5039. (d) Ho, C.-M.; Yu, W.-Y.; Che,
C.-M. Angew. Chem. Int. Ed. 2004, 43, 3303. (e) Sato, K.;
Aoki, M.; Noyori, R. Science 1998, 281, 1646. (f) Rajabi, F.;
In conclusion, we have reported a photooxidative alkene
cleavage reaction under an air atmosphere using catalytic
molecular iodine, trifluoroacetic acid, and visible light ir-
radiation. This novel reaction is valuable because it uses
inexpensive and harmless molecular oxygen from air and
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 884–888

8
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A. Fujiya et al.
LETTER
Karimi, N.; Saidi, M. R.; Primo, A.; Varma, R. S.; Luque, R.
Adv. Synth. Catal. 2012, 354, 1707. (g) Anand, N.; Reddy,
K. H. P.; Rao, K. S. R.; Burri, D. R. Catal. Lett. 2011, 141,
Miura, T.; Itoh, A. Synlett 2010, 2335. (e) Nakayama, H.;
Itoh, A. Tetrahedron Lett. 2007, 48, 1131. (f) Nakayama, H.;
Itoh, A. Chem. Pharm. Bull. 2006, 54, 1620.
1
355. (h) Wang, A.; Jiang, H. J. Org. Chem. 2010, 75, 2321.
(16) (a) Nobuta, T.; Fujiya, A.; Hirashima, S.; Tada, N.; Miura,
T.; Itoh, A. Tetrahedron Lett. 2012, 53, 5306. (b) Hirashima,
S.; Nobuta, T.; Tada, N.; Miura, T.; Itoh, A. Org. Lett. 2011,
13, 2576.
(17) Itoh, A.; Kodama, T.; Masaki, Y.; Inagaki, S. Synlett 2002,
522.
(
(
(
5) Wu, X.; Davis, A. P.; Fry, A. J. Org. Lett. 2007, 9, 5633.
6) Miao, C.-X.; Yu, B.; He, L.-N. Green Chem. 2011, 13, 541.
7) Miyamoto, K.; Sei, Y.; Yamaguchi, K.; Ochiai, M. J. Am.
Chem. Soc. 2009, 131, 1382.
8) (a) Photochemistry of Organic Compounds: From Concepts
to Practice; Klán, P.; Wirz, J., Eds.; John Wiley & Sons:
New York, 2009. (b) Hoffmann, N. Chem. Rev. 2008, 108,
(
(18) Hirashima, S.; Kudo, Y.; Nobuta, T.; Tada, N.; Itoh, A.
Tetrahedron Lett. 2009, 50, 4328.
1
052.
(19) Conversions of alkenes into aldehydes in the presence of
iodine under aerobic photooxidative conditions have been
reported previously, see: (a) Hewgill, F. R. Aust. J. Chem.
1994, 47, 461. (b) Liu, L.; Yang, B.; Katz, T. J.; Poindexter,
N. K. J. Org. Chem. 1991, 56, 3769.
(
9) For recent reviews, see: (a) Punniyamurthy, T.; Velusamy,
S.; Iqbal, J. Chem. Rev. 2005, 105, 2329. (b) Mallat, T.;
Baiker, A. Chem. Rev. 2004, 104, 3037. (c) Stahl, S. S.
Angew. Chem. Int. Ed. 2004, 43, 3400. (d) Piera, J.;
Backvall, J.-E. Angew. Chem. Int. Ed. 2008, 47, 3506.
(20) Photooxidation; Typical Procedure
(
(
10) Bhalerao, U.; Sridhar, M. Tetrahedron Lett. 1993, 34, 4341.
11) (a) Yuan, Z.; Zheng, S.; Zeng, Y.; Chen, J.; Han, Y.; Li, Y.;
Li, Y. New J. Chem. 2010, 34, 718. (b) Fu, X.-G.; Zhang, L.-
P.; Wu, L.-Z.; Tung, C.-H. J. Photosci. 2003, 10, 175. (c) Li,
H.-R.; Wu, L.-Z.; Tung, C.-H. Tetrahedron 2000, 56, 7437.
12) Murthy, R. S.; Bio, M.; You, Y. Tetrahedron Lett. 2009, 50,
A solution of trans-4,4′-di-tert-butylstilbene (1a) (0.15
mmol), I (0.015 mmol), and TFA (0.03 mmol) in dry
2
MeOH–EtOAc (1:2 mL) was stirred in a Pyrex test-tube
under air (open), and externally irradiated with four 22 W
fluorescent lamps for 20 h. The mixture was quenched with
aq Na S O solution and extracted with EtOAc (3 × 5 mL).
(
(
2
2
3
1041.
The combined organic layer was washed with brine (20 mL)
13) (a) Feng, K.; Peng, M.-L.; Wang, D.-H.; Zhang, L.-P.; Tung,
C.-H.; Wu, L.-Z. Dalton Trans. 2009, 9794. (b) Feng, K.;
Zhang, R.-Y.; Wu, L.-Z.; Tu, B.; Peng, M.-L.; Zhang, L.-P.;
Zhao, D.; Tung, C.-H. J. Am. Chem. Soc. 2006, 128, 14685.
14) Baucherel, X.; Uziel, J.; Juge, S. J. Org. Chem. 2001, 66,
and aq HCl (2 M, 2 × 20 mL), dried over MgSO and
4
concentrated in vacuo. Purification of the crude residue by
column chromatography (hexane–EtOAc, 50:1) provided 4-
tert-butylbenzaldehyde (2a) (41.1 mg, 84%).
(
(
(21) For heterolytic carbon–carbon bond cleavage reactions of
hydroperoxides in methanol, see: Utaka, M.; Fujita, Y.;
Takeda, A. Chem. Lett. 1982, 1607.
(22) Homolytic carbon–carbon bond cleavage reactions of
hydroperoxides cannot be ruled out, see: Gu, X.; Zhang, W.;
Salomon, R. G. J. Org. Chem. 2012, 77, 1554.
4504.
15) (a) Nobuta, T.; Fujiya, A.; Tada, N.; Miura, T.; Itoh, A.
Synlett 2012, 23, 2975. (b) Tada, N.; Ishigami, T.; Cui, L.;
Ban, K.; Miura, T.; Itoh, A. Tetrahedron Lett. 2013, 54, 256.
(c) Kanai, N.; Nakayama, H.; Tada, N.; Itoh, A. Org. Lett.
2010, 12, 1948. (d) Nobuta, T.; Hirashima, S.; Tada, N.;
Synlett 2014, 25, 884–888
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