4578
T. Nobuta et al. / Tetrahedron Letters 51 (2010) 4576–4578
hν
hν, O2
Br2
1)
HBr
Br
Ar
Br
Br
HBr
or
OO
OOH
HBr Br2
OH
solvent
O2
Br
Br
Br
Br
Ar
Ar
Ar
Ar
Ar
Ar
Ar
8
5
4
6
7
path a
HBr
or
Br2
solvent
O
Br
path b
Br
Br
HBr
or
H2O
OO
OOH
solvent
O2
Br
Br
Br
Ar
Ar
Br
Br
10
Br
11
9
Scheme 3. Plausible path of aerobic photo-oxidative synthesis of a,a-dibromoacetophenones.
yields regardless of an electron-donating or electron-withdrawing
group on the benzene ring (entries 1–6). Interestingly, methyl
groups on benzene ring are inert under the oxidation condition
(entry 4).12b,c Disubstituted aromatic alkynes, such as 1-phenyl-
1-propyne and 1-phenyl-1-hexyne produce the corresponding
acetophenone (path b). We think that this reaction mainly pro-
ceeds through path a, since -dibromoacetophenone (2) was
produced only in 29% yield when using b-bromostyrene (4) as
a,a
the substrate (Scheme 2).
In conclusion, we have developed the aerobic photo-oxidative
a
,
a
-dibromoketones in good yields (entries 7 and 8). Moreover,
2-ethynylpyridine, a heterocyclic compound, is also converted to
the corresponding -dibromoketones in modest yield (entry 9).
Aliphatic alkyne, such as 1-decyne, affords the corresponding
-dibromoketone with a low yield when EtOAc is used as a sol-
syntheses of a,a-dibromoacetophenones in the presence of 48%
aq HBr. This method is advantageous from the viewpoint of green
chemistry and organic synthesis due to using inexpensive bromine
sources, harmless visible light irradiated from a general purpose
fluorescent lamp, and molecular oxygen. Further application of this
photo-oxidation to other reactions is now in progress in our
laboratory.
a,a
a,a
vent (entry 10).
To clarify the reaction mechanism, aerobic photo-oxidations of
phenacyl bromide (3) in the presence of 1 equiv of 48% aq HBr or
Br2 were examined, and the desired
a,a-dibromoacetophenone
References and notes
(2) was obtained in low yield or not detected, respectively,
(Scheme 2). These results suggest that phenacyl bromide (3) is
not a direct intermediate in this reaction. Furthermore, the reac-
tion of b-bromostyrene (4) under the same conditions afforded 2
in 29% yield (Scheme 2). In addition, we infer that the yellow color
of the reaction mixture indicates the formation of bromine in the
reaction.
1. Kim, K.; Cho, J.; Yoon, S. C. J. Chem. Soc., Perkin Trans. 1 1995, 253.
2. (a) Fujiwara, J.; Matsumura, A.; Matsuoka, Y.; Kiji, J. Bull. Chem. Soc. Jpn. 1976,
49, 829; (b) Kawabata, N.; Fuji, T.; Naka, M.; Yamashita, S. Bull. Chem. Soc. Jpn.
1977, 50, 1005.
3. (a) Kowalski, C. J.; Fields, K. W. J. Am. Chem. Soc. 1982, 104, 321; (b) Zhdankin, V.
V.; Stang, P. J. Tetrahedron Lett. 1993, 34, 1461.
4. (a) Taylor, W. J. Chem. Soc. 1937, 304; (b) Ghiaci, M.; Asghari, J. Bull. Chem. Soc.
Jpn. 2001, 74, 1151; (c) Rahman, M. T.; Kamata, N.; Matsubara, H.; Ryu, I. Synlett
2005, 2664.
Scheme 3 shows a plausible path of this oxidation, which is pos-
tulated by considering all the results mentioned above and the
necessity of molecular oxygen and continuous irradiation in this
reaction. We assume that the vinyl radical species 5 is generated
by the addition of bromine radical to aromatic alkynes. The bro-
mine radical is formed under the irradiation of visible light from
bromine generated by aerobic photo-oxidation of the HBr. Positive
evidence remains elusive; however, we think there are two paths
(path a and b) which involve the formation of both peroxy radical
species 6 and b-bromostyrene (4). Peroxy radical species 6 ab-
stracts the hydrogen from HBr or solvent, and hydroperoxide 7 is
reduced by HBr to provide bromoenol 8. Finally, molecular bro-
5. Terent’ev, A. O.; Khodykin, S. V.; Krylov, I. B.; Ogibin, Y. N.; Nikishin, G. I.
Synthesis 2006, 1087.
6. (a) Kajigaeshi, S.; Kakinami, T.; Tokiyawa, H.; Hirakawa, T. Bull. Chem. Soc. Jpn.
1987, 60, 2667; (b) Paul, S.; Guptahedron, V.; Gupta, R.; Loupy, A. Tetrahedron
Lett. 2003, 44, 439.
7. Magen, S.; Oren, J.; Fuchs, B. Tetrahedron Lett. 1984, 25, 3369.
8. Al-Mousawi, S. M.; Bhatti, I.; Saraf, S. D. Org. Prep. Proceed. Int. 1992, 24, 60.
9. (a) Conte, V.; Floris, B.; Galloni, P.; Silvagni, A. Adv. Synth. Catal. 2005, 347, 1341;
(b) Conte, V.; Floris, B.; Silvagni, A. ACS Symp. Ser. 2007, 974, 28.
10. Ye, C.; Shreeve, J. M. J. Org. Chem. 2004, 69, 8561.
11. Masuda, H.; Takase, K.; Nishio, M.; Hasegawa, A.; Nishiyama, Y.; Ishii, Y. J. Org.
Chem. 1994, 59, 5550.
12. (a) Hirashima, S.; Itoh, A. Green Chem. 2007, 9, 285; (b) Hirashima, S.; Itoh, A.
Photochem. Photobiol. Sci. 2007, 6, 521; (c) Hirashima, S.; Itoh, A. J. Synth. Org.
Chem. Jpn. 2008, 66, 748.
mine traps 8 to afford
a
,
a
-dibromoacetophenone (2) (path a). On
13. Typical procedure: A solution of phenylacetylene (1, 0.3 mmol), 48% aq HBr
(0.63 mmol), and H2O (50 lL) in dry MeCN (5 mL) in a pyrex test tube, purged
the other hand, benzyl radical species 9 is generated by the addi-
tion of bromine radical to b-bromostyrene (4). The radical species
9 traps molecular oxygen to afford hydroperoxide 11 via peroxy
with an O2-balloon, was stirred and irradiated externally with four 22 W
fluorescent lamps for 10 h. The reaction mixture was washed with aq Na2S2O3
and brine, and concentrated in vacuo. Purification of the crude product by PTLC
(toluene) provided a,a-dibromoacetophenone (Rf = 0.70, 70.1 mg, 84%).
radical species 10. Finally, dehydration of 11 affords a,a-dibromo-