Catalytic aerobic photooxidative cleavage of carbon-carbon triple bonds using carbon tetrabromide

Article abstract of DOI:10.1055/s-0032-1318308

We developed the aerobic photooxidative cleavage of carbon-carbon triple bonds to carboxylic acids in the presence of catalytic amounts of carbon tetrabromide under photoirradiation with a high-pressure mercury lamp. Georg Thieme Verlag Stuttgart · New York..

Full text of DOI:10.1055/s-0032-1318308

LETTER
▌607
lCettaertalytic Aerobic Photooxidative Cleavage of Carbon–Carbon Triple Bonds
Using Carbon Tetrabromide
Aerobic Photooxidative Cleavage of C–C Triple Bonds
Tomoaki Yamaguchi, Tomoya Nobuta, Yasuhisa Kudo, Shin-ichi Hirashima, Norihiro Tada, Tsuyoshi Miura,
Akichika Itoh*
Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
Fax +81(58)2308108; E-mail: itoha@gifu-pu.ac.jp
Received: 07.01.2013; Accepted after revision: 01.02.2013
We have been studying the aerobic photooxidation of var-
ious substrates and have already reported the oxidative
Abstract: We developed the aerobic photooxidative cleavage of
carbon–carbon triple bonds to carboxylic acids in the presence of
catalytic amounts of carbon tetrabromide under photoirradiation
with a high-pressure mercury lamp.
9
cleavage of carbon–carbon double bonds with catalytic
1
0
amounts of a bromine source under photoirradiation.
In
the course of further studying this reaction, we found that
the oxidative cleavage of the carbon–carbon triple bonds
occurred in the presence of catalytic amounts of carbon
Key words: photooxidation, aerobic, carbon tetrabromide, carbon–
carbon triple bond, carboxylic acid
tetrabromide (CBr ) and water under aerobic photoirradi-
4
ation conditions (Scheme 1). We report herein a detailed
study of this photooxidative cleavage of alkynes.
The oxidative cleavage of a carbon–carbon triple bond to
the corresponding carboxylic acid is an important trans-
formation of functional groups in organic synthesis. In
1
O2, hν
CBr4 (cat.)
general, ozonolysis has been used for this purpose; how-
ever, ozone is toxic and requires the use of special equip-
ment to generate it. Thus, many oxidative cleavage
reactions using heavy-metal catalysts such as ruthenium,
osmium, iron, and indium in combination with stoichio-
metric amounts of oxygen donors such as TBHP, oxone,
O
O
R1
R2
+
H2O, EtOAc
R1
R2
OH
HO
Scheme 1 Aerobic oxidative cleavage of alkynes
2
To explore this approach, we selected phenylacetylene
1a) as the test substrate to optimize the reaction condi-
H O , and NaIO have been reported to date. In addition,
2
2
4
(
few metal-free reactions have been reported. Electron-de-
ficient acetylene can be cleaved using H O in the pres-
tions (Table 1). First, we screened the bromine sources
and solvents in the presence of molecular oxygen under
photoirradiation from a 400 W mercury lamp (Table 1, en-
tries 1–19). Benzoic acid (2a) was produced most effi-
2
2
3
ence of MeONa. Furthermore, stoichiometric amounts of
hypervalent iodine reagent C F I(OCOCF ) have been
used for this reaction. Recently, Ochiai’s group reported
the catalytic oxidative cleavage of carbon–carbon triple
6
5
3 2
4
ciently albeit in moderate yields when using CBr as
4
catalyst and ethyl acetate as solvent (Table 1, entry 1).
Next, the addition of trifluoroacetic acid (TFA) and potas-
sium carbonate (K CO ) was examined, and the yield in-
bonds using catalytic amounts of iodomesitylene and
MCPBA as the terminal oxidant.5
2
3
Owing to the increasing demand for more environmental-
ly benign synthesis, molecular oxygen has received much
attention as the ultimate oxidant, because it is photosyn-
thesized by plants, produces little waste, is inexpensive,
creased to 81% with the addition of K CO (Table 1,
2
3
entries 20 and 21). Interestingly, addition of water (150
μL) afforded the same yield of 2a (Table 1, entry 23). No
2a was obtained when a fluorescent lamp was used in-
6
and exhibits higher atom efficiency than other oxidants.
stead of a Hg lamp (Table 1, entry 25). The fact that 2a
However, autoxidation of carbon–carbon triple bonds is
slow even under high temperature and gives the corre-
was not obtained without CBr , photoirradiation, or mo-
4
lecular oxygen shows how critical these ingredients are
for this reaction (Table 1, entries 26–28).
7
sponding carboxylic acids in low yield. Recently, Jiang’s
group reported the palladium-catalyzed cleavage of car-
bon–carbon triple bonds to the corresponding esters using
Table 2 shows the results of scope and limitations of the
oxidative cleavage of alkynes under the above-mentioned
8
molecular oxygen as the terminal oxidant. To the best of
1
1
reaction conditions. Generally, the corresponding car-
boxylic acids are obtained in good to high yields regard-
less of the electron-donating or electron-withdrawing
group on the benzene ring (Table 2, entries 1–7). In addi-
tion, the ethynyl group is more easily oxidized to carbox-
ylic acid than the methyl group, and 4-methylbenzoic acid
was obtained in 52% yield (Table 2, entry 3). Further-
more, internal alkynes 1h, 1i, and 1j were also oxidized to
our knowledge, there is no catalytic oxidative cleavage re-
action of carbon–carbon triple bonds under metal-free
conditions using molecular oxygen as the terminal oxi-
dant.
SYNLETT 2013, 24, 0607–0610
2a in moderate to good yields (Table 2, entries 8–10). Un-
Advanced online publication: 18.02.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1318308; Art ID: ST-2013-U0018-L
Georg Thieme Verlag Stuttgart · New York
fortunately, no 2-picolinic acid was obtained (Table 2, en-
©

608
T. Yamaguchi et al.
LETTER
Table 1 Study of Reaction Conditionsa
try 11). On the other hand, 3-ethynylthiophene was
converted into 3-thiophenecarboxylic acid albeit in low
yield (Table 2, entry 12). Aliphatic alkyne was also con-
verted into the corresponding carboxylic acid in modest
yield (Table 2, entry 13).
O
O2, hν (400 W Hg lamp)
catalyst, additive
OH
solvent, 10 h
1a
2a
Table 2 Scope and Limitationsa
Entry Catalyst (equiv) Additive
Solvent
Yield
b
O2, hν (400 W Hg lamp)
CBr4 (0.1 equiv), H2O (150 mL)
(%)
substrate
product
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5c
6
CBr (0.1)
–
–
–
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
hexane
62
23
27
23
35
1
1
EtOAc
4
2
NBS (0.1)
Entry
1
Substrate
Time Yield
b
(
h)
(%)
Br (0.1)
2
1b R = OMe
20
10
5
40
10
20
40
78
71
52
62
86
90
97
48% aq HBr (0.1) –
c
2
3
1c R = t-Bu
1d R = Me
1e R = Ph
1a R = H
1f R = F
1g R = NO2
c
LiBr (0.1)
NaBr (0.1)
KBr (0.1)
–
–
–
4
5
6
7
R
1
MgBr ·OEt (0.1) –
23
32
27
38
15
52
10
20
34
33
32
8
2
2
R
d
8
9
1h R = Ph
1i R = Me
40
20
20
56
83
75
AlBr (0.1)
–
e
3
f
1
1
0
1j R = CO Et
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
SmBr (0.1)
–
3
CBr (0.1)
–
N
4
1
1k
20
0
CBr (0.1)
–
i-Pr O
4
2
CBr (0.1)
–
benzene
CH Cl
4
1
2
3
1l
20
40
16
34
S
CBr (0.1)
–
4
2
2
CBr (0.1)
–
acetone
MeCN
AcOH
MeOH
4
1
1m
H17C8
CBr (0.1)
–
4
a
A solution of substrate (1a, 0.3 mmol), CBr (0.1 equiv), and H O
CBr (0.1)
–
4
2
4
(
150 μL) in dry EtOAc (5 mL) purged with an O balloon was stirred
and irradiated externally with a 400 W high-pressure mercury lamp.
2
CBr (0.1)
–
4
b
Isolated yields.
CBr (0.1)
–
H O
c
4
2
The reaction was carried out with CBr (0.05 equiv).
4
d
Benzoic acid (0.34 mmol) was obtained.
Benzoic acid (0.25 mmol) was obtained.
Benzoic acid (0.225 mmol) was obtained.
CBr (0.1)
TFA (0.5 equiv)
EtOAc
59
81
59
e
4
f
CBr (0.1)
K CO (0.5 equiv) EtOAc
2 3
4
CBr (0.1)
H O (50 μL)
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
4
2
We studied the time course of the oxidative cleavage of 1a
to clarify the reaction mechanism in the presence or ab-
sence of water (Figure 1 and Figure 2). H NMR spectros-
copy was used to detect 2,2-dibromoacetophenone (3a)
and phenylglyoxylic acid (4a) under both conditions. Un-
fortunately, in the absence of water, only benzoic acid
CBr (0.1)
H O (150 μL)
81 (86)
4
2
1
CBr (0.05)
H O (150 μL)
79
0
4
2
CBr (0.1)
H O (150 μL)
4
2
–
H O (150 μL)
0
2
(
2a) was obtained, and the other products could not be de-
7d
CBr (0.1)
H O (150 μL)
0
1
4
2
termined by H NMR spectroscopy and GC–MS within
ten hours (Figure 2). Next, 3a was used as a substrate un-
der the optimal conditions to give 2a and ethyl benzoate
5a) regardless of the presence or absence of CBr4
Scheme 2, eq. 1). Furthermore, 4a afforded 2a and 5a in
8e
2
CBr (0.1)
H O (150 μL)
0
4
2
a
A solution of phenylacetylene (1a, 0.3 mmol), catalyst, and additive
(
(
in dry solvent (5 mL) purged with an O balloon was stirred and irra-
2
diated externally with a 400 W high-pressure mercury lamp for 10 h.
b 1
c
the presence of CBr in 80% and 19% yield, respectively
H NMR yields. Number in parentheses is isolated yield.
The reaction was carried out using fluorescent lamp.
The reaction was carried out in the dark.
4
(Scheme 2, eq. 2). These results suggest that 3a and 4a are
reaction intermediates.
d
e
The reaction was carried out under argon.
Scheme 3 shows a plausible path for the oxidative cleav-
age of alkynes, which is postulated by considering the de-
Synlett 2013, 24, 607–610
© Georg Thieme Verlag Stuttgart · New York

LETTER
Aerobic Photooxidative Cleavage of C–C Triple Bonds
609
tected intermediates and by the necessity of continuous
irradiation, a bromine source, and molecular oxygen for
this reaction. The bromo radical, generated by the homo-
lysis of CBr during photoirradiation, was added to 1 to af-
4
ford vinyl radical 6, which traps the molecular oxygen to
provide dibromoketone 3 via bromination of bromoenol 8
with the bromine or hypobromous acid. Because dibromo-
ketone 3a was oxidized to carboxylic acid in the absence
of CBr (Scheme 2, eq. 1), dibromoketone 3 was probably
4
converted into 1,2-dicarbonyl compound 12 via the homo-
lytic cleavage of the C–Br bond to 9 and the subsequent
oxidation (path A). In the case of terminal alkyne, 1,2-di-
carbonyl compound 12 was oxidized to glyoxylic acid 4.
Compound 4 was homolytically cleaved to acyl radical
1
2
15
via the Norrish type I reaction by photoirradiation
and oxidized to carboxylic acid via percarboxylic acid 16.
On the other hand, in the case of internal alkyne, 1,2-di-
ketone 12 was homolytically cleaved to acyl radical 15 via
the Norrish type I reaction. Under these conditions, the di-
Figure 1 Time course of oxidative cleavage of alkyne in the presence rect formation of acyl radical 15 from 3 is also possible via
of H O
2
the Norrish type I reaction (path B). Furthermore, abstrac-
tion of hydrogen of 3 by bromine radical to 17 is not also
ruled out (path C).
In conclusion, we developed the aerobic photooxidative
cleavage of carbon–carbon triple bonds to carboxylic ac-
ids using catalytic amounts of carbon tetrabromide in the
presence of water under photoirradiation from a high-
pressure mercury lamp. Furthermore, detailed mechanis-
tic studies, which include the role of additive water, are
ongoing in our laboratory.
Acknowledgment
This work was supported by Grant-in-Aid for Young Scientists (B)
(No. 24790015) from the Japan Society for the Promotion of Sci-
ence (JSPS). The authors would like to thank Enago (www.ena-
go.jp) for the English language review.
References and Notes
Figure 2 Time course of oxidative cleavage of alkyne in the absence
(
1) Comprehensive Organic Transformations; Larock, R. C.,
Ed.; 2nd ed.; Wiley: New York, 1999, 1636.
of H O
2
(
2) Recent reports, see: (a) Shaikh, T. M.; Hong, F.-E. Adv.
Synth. Catal. 2011, 353, 1491. (b) Enthaler, S.
O2, hν (400 W Hg lamp)
O
O
O
H2O (150 mL)
Br
OH
OEt
(1)
EtOAc (5 mL), 10 h
Br
3a
2a
65%
57%
5a
27%
26%
3a
0%
0%
with CBr4 (0.1 equiv)
without CBr4
O
O2, hν (400 W Hg lamp)
O
O
OH
H2O (150 mL)
OH
OEt
(2)
EtOAc (5 mL), 10 h
O
4a
2a
80%
44%
5a
19%
0%
4a
0%
0%
with CBr4 (0.1 equiv)
without CBr4
Scheme 2 Study of reaction intermediate
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 607–610

610
T. Yamaguchi et al.
LETTER
H2O
hν
hν
CBr4
CBr3
+
Br
Br2
HOBr
Br
+
HBr
Br2 or
HOBr
OOH
OH
O2
HBr
Br
Br
Br
Br
R
R
+ H
R
R
1
6
7
HOBr
8
O
path C
Br
O
O
R
O
O2
HBr
Br
Br
Br
OH
R
R
R
+
H
OOH
Br
Br
17
Br
Br
19
HBr
HOBr
3
18
path B
hν
path A
hν
HBr
O
O
O
O
H2O
hν
OH
Br
Br
R
R
R
R
15
O
O
9
HBr
4
20
O2 + H
O2 + H
HBr
HOBr
O
O
O
O
HBr
Br
OOH
OOH
R
R
R
OOH
R
OH
O
14
HOBr
1
0
16
2
HBr
O2
HOBr
+
H
O
O
O
Br
Br
R
R
R
OH
1
O
O
HBr
HBr
1
12
13
Scheme 3 Plausible reaction mechanism
ChemCatChem 2011, 3, 1929. (c) Kumar, V. A.; Reddy, V.
P.; Sredhar, R.; Srinivas, B.; Rao, R. Synlett 2009, 739.
(8) Wang, A.; Jiang, H. J. Am. Chem. Soc. 2008, 130, 5030.
(9) For recent reports, see: (a) Tada, N.; Ikebata, Y.; Nobuta, T.;
Hirashima, S.; Miura, T.; Itoh, A. Photochem. Photobiol.
Sci. 2012, 11, 616. (b) Tada, N.; Shomura, M.; Cui, L.;
Nobuta, T.; Miura, T.; Itoh, A. Synlett 2011, 2896. (c) Cui,
L.; Tada, N.; Okubo, H.; Miura, T.; Itoh, A. Green Chem.
2011, 13, 2347. (d) Tada, N.; Ban, K.; Nobuta, T.;
(d) Ranu, B. C.; Bhadra, S.; Adak, L. Tetrahedron Lett.
2
008, 49, 2588. (e) Samanta, S.; Adak, L.; Jana, R.; Mostafa,
G.; Tuononen, H. M.; Ranu, B. C.; Goswami, S. Inorg.
Chem. 2008, 47, 11062. (f) Che, C.-M.; Yip, W.-P.; Yu,
W.-Y. Chem. Asian J. 2006, 1, 453. (g) Yang, D.; Chen, F.;
Dong, Z.-M.; Zhang, D.-W. J. Org. Chem. 2004, 69, 2221.
Hirashima, S.; Miura, T.; Itoh, A. Synlett 2011, 1381.
(e) Tada, N.; Hattori, K.; Nobuta, T.; Miura, T.; Itoh, A.
Green Chem. 2011, 13, 1669. (f) Nobuta, T.; Hirashima, S.;
Tada, N.; Miura, T.; Itoh, A. Org. Lett. 2011, 13, 2576.
(g) Tada, N.; Matsusaki, Y.; Miura, T.; Itoh, A. Chem.
Pharm. Bull. 2011, 59, 906. (h) Tada, N.; Ban, K.; Ishigami,
T.; Nobuta, T.; Miura, T.; Itoh, A. Tetrahedron Lett. 2011,
52, 3821. (i) Nobuta, T.; Tada, N.; Hattori, K.; Hirashima,
S.; Miura, T.; Itoh, A. Tetrahedron Lett. 2011, 52, 875.
(h) Griffith, W. P.; Kwong, E. Synth. Commun. 2003, 33,
2945. (i) Cornely, J.; Ham, L. M. S.; Meade, D. E.;
Dragojlovic, V. Green Chem. 2003, 5, 34. (j) Lee, K.; Kim,
Y.-H.; Han, S. B.; Kang, H.; Park, S.; Seo, W. S.; Park, J. T.;
Kim, B.; Chang, S. J. Am. Chem. Soc. 2003, 125, 6844.
(
k) Griffith, W. P.; Shoair, A. G.; Suriaatmaja, M. Synth.
Commun. 2000, 30, 3091.
(
3) Sawaki, Y.; Inoue, H.; Ogata, Y. Bull. Chem. Soc. Jpn. 1983,
5
6, 1133.
(10) Hirashima, S.; Kudo, Y.; Nobuta, T.; Tada, N.; Itoh, A.
Tetrahedron Lett. 2009, 50, 4328.
(11) General Procedure
(
4) (a) Moriarty, R. M.; Penmasta, R.; Awasthi, A. K.; Prakash,
I. J. Org. Chem. 1988, 53, 6124. (b) Yusubov, M. S.;
Zholobova, G. A.; Filimonova, I. L.; Chi, K.-W. Russ.
Chem. Bull. Int. Ed. 2004, 53, 1735.
A solution of phenylacetylene (1a, 0.3 mmol), CBr (0.03
4
mmol), and H O (150 μL) in dry EtOAc (3 mL) in a Pyrex
2
(
5) Miyamoto, K.; Sei, Y.; Yamaguchi, K.; Ochiai, M. J. Am.
Chem. Soc. 2009, 131, 1382.
test tube, purged with an O balloon, was stirred and
2
irradiated externally with a 400 W high-pressure mercury
lamp for 10 h. The reaction mixture was concentrated in
vacuo, and 10% aq NaOH was added. The aqueous solution
(
6) For a recent review, 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.
7) (a) Pratzkow, W.; Rao, T. S. S. J. Prakt. Chem. 1985, 327,
was washed with CHCl , and then acidified with 2 N aq HCl
3
solution, which was extracted with CHCl . The organic layer
3
was dried over MgSO , and concentrated in vacuo provided
4
(
benzoic acid (31.4 mg, 86%).
8
2
87. (b) Rao, T. S. S.; Awasthi, S. J. Indian Chem. Soc.
003, 80, 1129.
(12) For the review on acyl radicals, see: Chatgilialoglu, C.;
Crich, D.; Komatsu, M.; Ryu, I. Chem. Rev. 1999, 99, 1991.
Synlett 2013, 24, 607–610
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