- Email: [email protected]
Facile aerobic photo-oxidative synthesis of α-diketones from alkynes
Tetrahedron Letters 52 (2011) 875–877
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Facile aerobic photo-oxidative synthesis of a-diketones from alkynes Tomoya Nobuta, Norihiro Tada, Kasumi Hattori, Shin-ichi Hirashima, Tsuyoshi Miura, Akichika Itoh ⇑ Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 27 September 2010 Revised 3 December 2010 Accepted 8 December 2010 Available online 13 December 2010
We report a useful method for facile aerobic photo-oxidative synthesis of a-diketones from alkynes with MgBr2OEt2. This procedure provides a practical synthetic method of a-diketones using easily handled bromine sources, harmless visible light, and molecular oxygen as terminal oxidant. Ó 2010 Elsevier Ltd. All rights reserved.
Keywords: Aerobic Photo-oxidation MgBr2OEt2 a-Diketones Alkynes
a-Diketones play an important role as versatile building blocks in organic synthesis. For example, they react with 3-oxoglutarates to afford cis-bicyclo[3.3.0]octane-3,7-diones1 that are precursors of polyquinanes. a-Diketones also have been used as precursors of various heteroaromatics, since they react with acyl hydrazides or 1,2-diaminobenzenes that result in 1,2,4-triazines2 or quinoxalines,3 respectively. Moreover, 2,4,5-trisubstituted imidazoles, having pharmaceutical activities, can be prepared by coupling with aldehydes.4 Most popular syntheses of a-diketones are the oxidation of alkynes which can be easily obtained by Sonogashira coupling; however, the oxidations require rare metal reagents (Mn,5 Cr,6 Ru,7 Re8 or Pd9), high temperature,10 large excess of strong acid11,12 or expensive halogen sources,13 and complex and intractable reagents.14,15 As such, from the green chemistry angle, more environmentally friendly synthetic methods of a-diketones are in demand. With these perspectives, we have studied environmentally benign oxidation with molecular oxygen, and already reported aerobic photo-oxidative syntheses of carboxylic acids from methyl aromatics or alcohols in the presence of catalytic amounts of MgBr2OEt2.16 In the course of our additional studies of this photo-oxidation, we also found that alkynes are oxidized to their corresponding a-diketones successfully under similar
Scheme 1.
Table 1 Study of reaction conditions for aerobic photo-oxidation
E-mail address: [email protected] (A. Itoh). 0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2010.12.029
Bromine source (equiv)
Solvent
Time (h)
Yielda (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (0.2) MgBr2OEt2 (0.5) MgBr2OEt2 (1.5) MgBr2OEt2 (–) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) Br2 (1.0) aq. HBr (1.0) LiBr (1.0) NaBr (1.0) AlBr3 (1.0) NiBr2 (1.0) SrBr2 (1.0) SmBr2 (1.0) YbBr3 (1.0)
Acetone CH2Cl2 Benzene THF Hexane EtOAc MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN
20 20 20 20 20 20 20 24 24 24 24 24 24 24 20 20 20 20 20 20 20 20 20
9 13 14 17 31 48 51 71b 21 45 54 n.r. n.r.c n.r.d 5 36 3 n.r. 32 31 11 55 36
a 1 b
⇑ Corresponding author.
Entry
c d
H NMR analysis. Isolated yield. The reaction was carried out in the dark. The reaction was carried out under Ar atmosphere.
876
T. Nobuta et al. / Tetrahedron Letters 52 (2011) 875–877
Table 2 Aerobic photo-oxidative synthesis of a-diketones from alkynes
substrate (0.3 mmol) Entry
Substrate
O 2, hν (VIS) MgBr 2·OEt 2
product
MeCN (5 mL), 24 h MgBr2OEt2 (equiv)
Yielda (%)
Product
O 1.0
1
71
O O
Cl 2
1.0
Cl
70
O O
Br 1.5
3
Br
60
O O
Ac 4
1.5
Ac
68
O O
O2N 1.5
5
O 2N
56
O O 2N
O2N O 1.0
6
56
O O
MeO 1.0
7
MeO
30b
O O
Me 8
1.5
Me
56
O Me
Me O 1.0
9
n.r.
O O 10
1.0
N
33
N O O
11
1.0
N
O O
Bu 12
32
N
1.0
C6H11
Bu
C6H11
13
n.r.
O O 1.0
C6H11 C6 H11
n.r.
O a b
Isolated yields. 31% of starting material was recovered.
conditions (Scheme 1). This novel method is interesting in a view point of green chemistry due to the use of harmless visible light from general-purpose fluorescent lamp, molecular oxygen as terminal oxidants, and easily handled bromine sources such as MgBr2OEt2. Herein, we report our detailed study of the aerobic photo-oxidative synthesis of a-diketones from alkynes. Table 1 shows the results of optimization of reaction conditions for aerobic photo-oxidation using diphenylacetylene (1) as a test
substrate.17 In this protocol, better results were obtained when using MgBr2OEt2 (1.0 equiv) as bromine sources and MeCN as solvent (entries 1–11 and 15–23).18 The fact that benzil (2) was not obtained without MgBr2OEt2, irradiation, or molecular oxygen shows the necessity of all of these ingredients for this reaction (entries 12–14). Table 2 presents the scope and limitation of this oxidation under the optimized reaction conditions mentioned above. In general,
877
T. Nobuta et al. / Tetrahedron Letters 52 (2011) 875–877
a,a-dibromoketones 7, which can be detected by 1H NMR. The corresponding a-diketones are given by hydrolysis of 7.
Table 3 Study of efficient wavelength of light
Ph
Ph
O2, hν (300 W Xe lamp) MgBr2·OEt 2 (1.0 equiv)
1 (0.3 mmol)
MeCN (5 mL), 24 h
In conclusion, we have developed a facile and practical method for the preparation of a-diketones by aerobic photo-oxidation of alkynes. This method is of great value from the view point of synthetic organic chemistry as a harmless visible light irradiation from a general purpose fluorescent lamp and molecular oxygen are used. Further application of this photooxidation to other reactions is now in progress in our laboratory.
O Ph
Ph O
2
Yielda (%)
Entry
hm (nm)
1 2 3 4 5 6 7
Xe lamp (all) 397 445 499 558 589 618
2
Recovery of 1
60 0 35 42 0 0 0
Trace 100 50 50 100 100 99
References and notes 1. Venkatachalam, M.; Deshpande, M. N.; Jawdosiuk, M.; Kubiak, G.; Wehrli, S.; Cook, J. M. Tetrahedron 1986, 42, 1597–1605. 2. Zhao, Z.; Leister, W. H.; Strauss, K. A.; Wisnoski, D. D.; Lindsley, C. W. Tetrahedron Lett. 2003, 44, 1123–1127. 3. Zhao, Z.; Wisnoski, D. D.; Wolkenberg, S. E.; Leister, W. H.; Wang, Y.; Lindsley, C. W. Tetrahedron Lett. 2004, 45, 4873–4876.
a 1
H NMR analysis.
O2 O2 (1)
(2)
MgBr2
Ar
HBr
Br
-
Br2 Br
Ar' + Br
Br2
H2O O2
Br
Ar
H O
Br
Ar 6
3
HBr
O2
Ar'
HBr
Ar' Br Br
OO Ar
O
Br Br Ar'
Ar
Br 4
H2O
Solvent or HBr
HOO
Ar' HBr
Ar
O Ar
Br 5
Ar'
O Ar'
7
Scheme 2. Plausible path of aerobic photo-oxidative syntheses of a-diketones
when diarylacetylenes are used as substrates, the corresponding adiketones were obtained in good to moderate yields with an electron-withdrawing group at para or meta position of the benzene ring; however, 4-methoxybiphenylacetylene, possessing an electron-donating group, was a poor substrate to give the corresponding a-diketone only in low yield (entries 1–8). For 2-methylbiphenylacetylene, possessing a methyl group at the ortho position of benzene ring, the product was not obtained under this condition (entry 9). In addition, 2-(2-phenylethynyl) pyridine and 3-(2-phenylethynyl) pyridine, heterocyclic compounds, produced the corresponding a-diketones in low yields, respectively (entries 10 and 11). Unfortunately, monoarylacetylenes, such as 1-phenyl-1-hexyne, and dialkylacetylenes, such as 6-undecyne, were intact under this condition (entries 12 and 13). Table 3 shows the results of the study of efficient wavelength for this aerobic photo-oxidative synthesis of a-diketones. Among our examination, visible lights, especially 445 nm and 499 nm, were effective for this reaction.19 Scheme 2 shows a plausible path of this oxidation, which is postulated by the necessity of molecular oxygen and continuous irradiation.20 Observation of yellow color in the reaction mixture suggests the generation of bromine in this reaction system. We guess that the vinyl radical species 3 is generated by the addition of bromine radical to alkynes. Bromine radical is formed by continuous aerobic photo-oxidation of the MgBr2OEt2. Mg2+ is thought to catalyze the electron transfer from bromine anion to oxygen, and also to stabilize O2 , which is generated by electron transfer from bromine anion under photo-irradiation, by the formation of their 1:1 complex.21 The radical species 3 traps molecular oxygen to afford hydroperoxides 5 through peroxy radical species 4. Hydroperoxides 5 are reduced by HBr, which is generated in situ, to provide bromoenols 6. Molecular bromine reacts with 6 to afford
4. Wolkenberg, S. E.; Wisnoski, D. D.; Leister, W. H.; Wang, Y.; Zhao, Z.; Lindsley, C. W. Org. Lett. 2004, 6, 1453–1456. 5. (a) Lee, D. G.; Chang, V. S. Synthesis 1978, 462–463; (b) Lee, D. G.; Lee, E. J.; Chandler, W. D. J. Org. Chem. 1985, 50, 4306–4309. 6. Sheats, W. B.; Olli, L. K.; Stout, R.; Lundeen, J. T.; Justus, R.; Nigh, W. G. J. Org. Chem. 1979, 44, 4075–4078. 7. (a) Gopal, H.; Gordon, A. J. Tetrahedron Lett. 1971, 31, 2941–2944; (b) Müller, P.; Godoy, J. Helv. Chim. Acta 1981, 64, 2531–2533; (c) Che, C.-M.; Yu, W.-Y.; Chan, P.-M.; Cheng, W.-C.; Peng, S.-M.; Lau, K.-C.; Li, W.-K. J. Am. Chem. Soc. 2000, 122, 11380–11392; (d) Ren, W.; Liu, J.; Chen, L.; Wan, X. Adv. Synth. Catal. 2010, 352, 1424–1428. 8. Zhu, Z.; Espenson, J. H. J. Org. Chem. 1995, 60, 7728–7732. 9. (a) Chi, K.-W.; Yusubov, M. S.; Filimonov, V. D. Synth. Commun. 1994, 24, 2119– 2122; (b) Ren, W.; Xia, Y.; Ji, S.-J.; Zhang, Y.; Wan, X.; Zhao, J. Org. Lett. 2009, 11, 1841–1844. 10. (a) Yusubov, M. S.; Filimonov, V. D. Synthesis 1991, 131–132; (b) Yusubov, M. S.; Filimonov, V. D.; Vasilyeva, V. P.; Chi, K.-W. Synthesis 1995, 1234–1236. 11. Wan, Z.; Jones, C. D.; Mitchell, D.; Pu, J. Y.; Zhang, T. Y. J. Org. Chem. 2006, 71, 826–828. 12. Chu, J.-H.; Chen, Y.-J.; Wu, M.-J. Synthesis 2009, 2155–2162. 13. Niu, M.; Fu, H.; Jiang, Y.; Zhao, Y. Synthesis 2008, 2879–2882. 14. Aronovitch, C.; Tal, D.; Mazur, Y. Tetrahedron Lett. 1982, 35, 3623–3626. 15. Dayan, S.; Ben-David, I.; Rozen, S. J. Org. Chem. 2000, 65, 8816–8818. 16. (a) Hirashima, S.; Itoh, A. Green. Chem. 2007, 9, 318–320; (b) Hirashima, S.; Itoh, A. Photochem. Photobiol. Sci. 2007, 6, 521; (c) Hirashima, S.; Itoh, A. J. Synth. Org. Chem. Jpn. 2008, 66, 748–756. 17. Typical procedure: A solution of diphenylacetylene (1, 0.3 mmol) and MgBr2OEt2 (0.3 mmol) in dry MeCN (5 mL) in a pyrex test tube, purged with an O2-balloon, is stirred and irradiated externally with four 22 W fluorescent lamps, which are equipped in the distance of 65 mm, for 24 h. The reaction mixture is washed with aq. Na2S2O3 and brine, concentrated in vacuo, and purified by PTLC. 18. When the reaction was carried out in the presence of catalytic amount of Br2 (0.2 equiv), benzil (2) was obtained only in 3% yield along with 70% of recovered diphenylacetylene (1) and a lot of by-products. Therefore, we think that Br2 was probably trapped by triple bond of diphenylacetylene (1) and the reaction did not proceed efficiently. 19. 300 W Xenon lamp (ASAHI SPECTRA MAX-301) was used. 20. The reaction did not proceed when 1.0 equiv of galvinoxyl, which is a radical scavenger, was added. 21. Fukuzumi, S.; Ohkubo, K. Chem. Eur. J. 2000, 6, 4532–4535.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Facile aerobic photo-oxidative synthesis of a-diketones from alkynes Tomoya Nobuta, Norihiro Tada, Kasumi Hattori, Shin-ichi Hirashima, Tsuyoshi Miura, Akichika Itoh ⇑ Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 27 September 2010 Revised 3 December 2010 Accepted 8 December 2010 Available online 13 December 2010
We report a useful method for facile aerobic photo-oxidative synthesis of a-diketones from alkynes with MgBr2OEt2. This procedure provides a practical synthetic method of a-diketones using easily handled bromine sources, harmless visible light, and molecular oxygen as terminal oxidant. Ó 2010 Elsevier Ltd. All rights reserved.
Keywords: Aerobic Photo-oxidation MgBr2OEt2 a-Diketones Alkynes
a-Diketones play an important role as versatile building blocks in organic synthesis. For example, they react with 3-oxoglutarates to afford cis-bicyclo[3.3.0]octane-3,7-diones1 that are precursors of polyquinanes. a-Diketones also have been used as precursors of various heteroaromatics, since they react with acyl hydrazides or 1,2-diaminobenzenes that result in 1,2,4-triazines2 or quinoxalines,3 respectively. Moreover, 2,4,5-trisubstituted imidazoles, having pharmaceutical activities, can be prepared by coupling with aldehydes.4 Most popular syntheses of a-diketones are the oxidation of alkynes which can be easily obtained by Sonogashira coupling; however, the oxidations require rare metal reagents (Mn,5 Cr,6 Ru,7 Re8 or Pd9), high temperature,10 large excess of strong acid11,12 or expensive halogen sources,13 and complex and intractable reagents.14,15 As such, from the green chemistry angle, more environmentally friendly synthetic methods of a-diketones are in demand. With these perspectives, we have studied environmentally benign oxidation with molecular oxygen, and already reported aerobic photo-oxidative syntheses of carboxylic acids from methyl aromatics or alcohols in the presence of catalytic amounts of MgBr2OEt2.16 In the course of our additional studies of this photo-oxidation, we also found that alkynes are oxidized to their corresponding a-diketones successfully under similar
Scheme 1.
Table 1 Study of reaction conditions for aerobic photo-oxidation
E-mail address: [email protected] (A. Itoh). 0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2010.12.029
Bromine source (equiv)
Solvent
Time (h)
Yielda (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) MgBr2OEt2 (0.2) MgBr2OEt2 (0.5) MgBr2OEt2 (1.5) MgBr2OEt2 (–) MgBr2OEt2 (1.0) MgBr2OEt2 (1.0) Br2 (1.0) aq. HBr (1.0) LiBr (1.0) NaBr (1.0) AlBr3 (1.0) NiBr2 (1.0) SrBr2 (1.0) SmBr2 (1.0) YbBr3 (1.0)
Acetone CH2Cl2 Benzene THF Hexane EtOAc MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN
20 20 20 20 20 20 20 24 24 24 24 24 24 24 20 20 20 20 20 20 20 20 20
9 13 14 17 31 48 51 71b 21 45 54 n.r. n.r.c n.r.d 5 36 3 n.r. 32 31 11 55 36
a 1 b
⇑ Corresponding author.
Entry
c d
H NMR analysis. Isolated yield. The reaction was carried out in the dark. The reaction was carried out under Ar atmosphere.
876
T. Nobuta et al. / Tetrahedron Letters 52 (2011) 875–877
Table 2 Aerobic photo-oxidative synthesis of a-diketones from alkynes
substrate (0.3 mmol) Entry
Substrate
O 2, hν (VIS) MgBr 2·OEt 2
product
MeCN (5 mL), 24 h MgBr2OEt2 (equiv)
Yielda (%)
Product
O 1.0
1
71
O O
Cl 2
1.0
Cl
70
O O
Br 1.5
3
Br
60
O O
Ac 4
1.5
Ac
68
O O
O2N 1.5
5
O 2N
56
O O 2N
O2N O 1.0
6
56
O O
MeO 1.0
7
MeO
30b
O O
Me 8
1.5
Me
56
O Me
Me O 1.0
9
n.r.
O O 10
1.0
N
33
N O O
11
1.0
N
O O
Bu 12
32
N
1.0
C6H11
Bu
C6H11
13
n.r.
O O 1.0
C6H11 C6 H11
n.r.
O a b
Isolated yields. 31% of starting material was recovered.
conditions (Scheme 1). This novel method is interesting in a view point of green chemistry due to the use of harmless visible light from general-purpose fluorescent lamp, molecular oxygen as terminal oxidants, and easily handled bromine sources such as MgBr2OEt2. Herein, we report our detailed study of the aerobic photo-oxidative synthesis of a-diketones from alkynes. Table 1 shows the results of optimization of reaction conditions for aerobic photo-oxidation using diphenylacetylene (1) as a test
substrate.17 In this protocol, better results were obtained when using MgBr2OEt2 (1.0 equiv) as bromine sources and MeCN as solvent (entries 1–11 and 15–23).18 The fact that benzil (2) was not obtained without MgBr2OEt2, irradiation, or molecular oxygen shows the necessity of all of these ingredients for this reaction (entries 12–14). Table 2 presents the scope and limitation of this oxidation under the optimized reaction conditions mentioned above. In general,
877
T. Nobuta et al. / Tetrahedron Letters 52 (2011) 875–877
a,a-dibromoketones 7, which can be detected by 1H NMR. The corresponding a-diketones are given by hydrolysis of 7.
Table 3 Study of efficient wavelength of light
Ph
Ph
O2, hν (300 W Xe lamp) MgBr2·OEt 2 (1.0 equiv)
1 (0.3 mmol)
MeCN (5 mL), 24 h
In conclusion, we have developed a facile and practical method for the preparation of a-diketones by aerobic photo-oxidation of alkynes. This method is of great value from the view point of synthetic organic chemistry as a harmless visible light irradiation from a general purpose fluorescent lamp and molecular oxygen are used. Further application of this photooxidation to other reactions is now in progress in our laboratory.
O Ph
Ph O
2
Yielda (%)
Entry
hm (nm)
1 2 3 4 5 6 7
Xe lamp (all) 397 445 499 558 589 618
2
Recovery of 1
60 0 35 42 0 0 0
Trace 100 50 50 100 100 99
References and notes 1. Venkatachalam, M.; Deshpande, M. N.; Jawdosiuk, M.; Kubiak, G.; Wehrli, S.; Cook, J. M. Tetrahedron 1986, 42, 1597–1605. 2. Zhao, Z.; Leister, W. H.; Strauss, K. A.; Wisnoski, D. D.; Lindsley, C. W. Tetrahedron Lett. 2003, 44, 1123–1127. 3. Zhao, Z.; Wisnoski, D. D.; Wolkenberg, S. E.; Leister, W. H.; Wang, Y.; Lindsley, C. W. Tetrahedron Lett. 2004, 45, 4873–4876.
a 1
H NMR analysis.
O2 O2 (1)
(2)
MgBr2
Ar
HBr
Br
-
Br2 Br
Ar' + Br
Br2
H2O O2
Br
Ar
H O
Br
Ar 6
3
HBr
O2
Ar'
HBr
Ar' Br Br
OO Ar
O
Br Br Ar'
Ar
Br 4
H2O
Solvent or HBr
HOO
Ar' HBr
Ar
O Ar
Br 5
Ar'
O Ar'
7
Scheme 2. Plausible path of aerobic photo-oxidative syntheses of a-diketones
when diarylacetylenes are used as substrates, the corresponding adiketones were obtained in good to moderate yields with an electron-withdrawing group at para or meta position of the benzene ring; however, 4-methoxybiphenylacetylene, possessing an electron-donating group, was a poor substrate to give the corresponding a-diketone only in low yield (entries 1–8). For 2-methylbiphenylacetylene, possessing a methyl group at the ortho position of benzene ring, the product was not obtained under this condition (entry 9). In addition, 2-(2-phenylethynyl) pyridine and 3-(2-phenylethynyl) pyridine, heterocyclic compounds, produced the corresponding a-diketones in low yields, respectively (entries 10 and 11). Unfortunately, monoarylacetylenes, such as 1-phenyl-1-hexyne, and dialkylacetylenes, such as 6-undecyne, were intact under this condition (entries 12 and 13). Table 3 shows the results of the study of efficient wavelength for this aerobic photo-oxidative synthesis of a-diketones. Among our examination, visible lights, especially 445 nm and 499 nm, were effective for this reaction.19 Scheme 2 shows a plausible path of this oxidation, which is postulated by the necessity of molecular oxygen and continuous irradiation.20 Observation of yellow color in the reaction mixture suggests the generation of bromine in this reaction system. We guess that the vinyl radical species 3 is generated by the addition of bromine radical to alkynes. Bromine radical is formed by continuous aerobic photo-oxidation of the MgBr2OEt2. Mg2+ is thought to catalyze the electron transfer from bromine anion to oxygen, and also to stabilize O2 , which is generated by electron transfer from bromine anion under photo-irradiation, by the formation of their 1:1 complex.21 The radical species 3 traps molecular oxygen to afford hydroperoxides 5 through peroxy radical species 4. Hydroperoxides 5 are reduced by HBr, which is generated in situ, to provide bromoenols 6. Molecular bromine reacts with 6 to afford
4. Wolkenberg, S. E.; Wisnoski, D. D.; Leister, W. H.; Wang, Y.; Zhao, Z.; Lindsley, C. W. Org. Lett. 2004, 6, 1453–1456. 5. (a) Lee, D. G.; Chang, V. S. Synthesis 1978, 462–463; (b) Lee, D. G.; Lee, E. J.; Chandler, W. D. J. Org. Chem. 1985, 50, 4306–4309. 6. Sheats, W. B.; Olli, L. K.; Stout, R.; Lundeen, J. T.; Justus, R.; Nigh, W. G. J. Org. Chem. 1979, 44, 4075–4078. 7. (a) Gopal, H.; Gordon, A. J. Tetrahedron Lett. 1971, 31, 2941–2944; (b) Müller, P.; Godoy, J. Helv. Chim. Acta 1981, 64, 2531–2533; (c) Che, C.-M.; Yu, W.-Y.; Chan, P.-M.; Cheng, W.-C.; Peng, S.-M.; Lau, K.-C.; Li, W.-K. J. Am. Chem. Soc. 2000, 122, 11380–11392; (d) Ren, W.; Liu, J.; Chen, L.; Wan, X. Adv. Synth. Catal. 2010, 352, 1424–1428. 8. Zhu, Z.; Espenson, J. H. J. Org. Chem. 1995, 60, 7728–7732. 9. (a) Chi, K.-W.; Yusubov, M. S.; Filimonov, V. D. Synth. Commun. 1994, 24, 2119– 2122; (b) Ren, W.; Xia, Y.; Ji, S.-J.; Zhang, Y.; Wan, X.; Zhao, J. Org. Lett. 2009, 11, 1841–1844. 10. (a) Yusubov, M. S.; Filimonov, V. D. Synthesis 1991, 131–132; (b) Yusubov, M. S.; Filimonov, V. D.; Vasilyeva, V. P.; Chi, K.-W. Synthesis 1995, 1234–1236. 11. Wan, Z.; Jones, C. D.; Mitchell, D.; Pu, J. Y.; Zhang, T. Y. J. Org. Chem. 2006, 71, 826–828. 12. Chu, J.-H.; Chen, Y.-J.; Wu, M.-J. Synthesis 2009, 2155–2162. 13. Niu, M.; Fu, H.; Jiang, Y.; Zhao, Y. Synthesis 2008, 2879–2882. 14. Aronovitch, C.; Tal, D.; Mazur, Y. Tetrahedron Lett. 1982, 35, 3623–3626. 15. Dayan, S.; Ben-David, I.; Rozen, S. J. Org. Chem. 2000, 65, 8816–8818. 16. (a) Hirashima, S.; Itoh, A. Green. Chem. 2007, 9, 318–320; (b) Hirashima, S.; Itoh, A. Photochem. Photobiol. Sci. 2007, 6, 521; (c) Hirashima, S.; Itoh, A. J. Synth. Org. Chem. Jpn. 2008, 66, 748–756. 17. Typical procedure: A solution of diphenylacetylene (1, 0.3 mmol) and MgBr2OEt2 (0.3 mmol) in dry MeCN (5 mL) in a pyrex test tube, purged with an O2-balloon, is stirred and irradiated externally with four 22 W fluorescent lamps, which are equipped in the distance of 65 mm, for 24 h. The reaction mixture is washed with aq. Na2S2O3 and brine, concentrated in vacuo, and purified by PTLC. 18. When the reaction was carried out in the presence of catalytic amount of Br2 (0.2 equiv), benzil (2) was obtained only in 3% yield along with 70% of recovered diphenylacetylene (1) and a lot of by-products. Therefore, we think that Br2 was probably trapped by triple bond of diphenylacetylene (1) and the reaction did not proceed efficiently. 19. 300 W Xenon lamp (ASAHI SPECTRA MAX-301) was used. 20. The reaction did not proceed when 1.0 equiv of galvinoxyl, which is a radical scavenger, was added. 21. Fukuzumi, S.; Ohkubo, K. Chem. Eur. J. 2000, 6, 4532–4535.