- Email: [email protected]
Bismuth-catalyzed synthesis of anthracenes via cycloisomerization of o-alkynyldiarylmethane
Tetrahedron Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Bismuth-catalyzed synthesis of anthracenes via cycloisomerization of o-alkynyldiarylmethane Jungmin Park a, Hyuck Choi a, Deug-Chan Lee b,c,⇑, Kooyeon Lee a,b,⇑ a
Department of Bio-Health Technology, Kangwon National University, Chuncheon 200-701, Republic of Korea Department of Medical Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea c Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea b
a r t i c l e
i n f o
Article history: Received 14 March 2015 Revised 26 October 2015 Accepted 30 October 2015 Available online xxxx
a b s t r a c t In this study, anthracenes were efficiently synthesized from o-alkynyldiarylmethane using a novel method that exploits the synergistic effect between Bi(OTf)3 as the catalyst, and trifluoroacetic acid (TFA). Through this reaction, we achieved the rapid and efficient synthesis of anthracenes bearing various functional groups under mild conditions. Ó 2015 Published by Elsevier Ltd.
Keywords: Anthracene Hydroarylation Bismuth Brønsted acid Catalysis
Polycyclic aromatic hydrocarbons (PAHs) are important compounds that have been attracting increasing attention in the material sciences for their wide range of applications, such as in photoelectronic devices.1 Anthracene derivatives have also been extensively studied as promising therapeutic agents,2 optical devices,3 and polymers.4 Anthracene compounds are commonly synthesized via a Bradsher-type reaction using 2-acyldiarylmethane in the presence of a Lewis acid.5 However, this reaction has disadvantages, including vigorous reaction conditions, low reaction yields, and a limited range of compatible functional groups. An effective method for the Au-catalyzed synthesis of anthracene derivatives via cycloisomerization of o-alkynyldiarylmethane has recently been reported.6 The disadvantage of this method is the use of an expensive gold catalyst and acid. Recently, a wide range of hydroarylations using Brønsted acid, Au-catalyst, etc. has been reported.7 We also reported that Fe or Bi can be used as an effective catalyst for alkyne activation.8 In particular, Bi has been widely used over the past several years in low-cost, lowtoxicity, and ecofriendly catalysts for organic synthesis.9 This Letter presents a novel method for efficiently synthesizing anthracene derivatives via Bi-catalyzed alkyne activation (Scheme 1). ⇑ Corresponding author. Tel.: +82 33 250 6488; fax: +82 33 250 6480 (D.-C.L.); tel.: +82 33 250 6477; fax: +82 33 250 6470 (K.L.). E-mail addresses: [email protected] (D.-C. Lee), [email protected] (K. Lee).
The reaction conditions were optimized using 1-benzyl-2ethynylbenzene (1a) as a model substrate (Table 1). The catalytic activities of various metal triflates (5 mol %) were investigated by starting material 1a at 60 °C using 1,2-dichloroethane as the solvent. The reaction of 1a did not proceed significantly with Sc (OTf)3 (Table 1, entry 1). The use of indium, copper, and iron catalysts resulted in the generation of the desired product (2a) with yields of 21%, 45%, and 46%, respectively. These low yields were verified by 1H NMR (Table 1, entries 2–4), and the hydration product 1-(2-benzylphenyl)ethanone (3a) was confirmed to be generated as a byproduct. When Bi(OTf)3 was used as the catalyst, 9-methylanthracene (2a) was obtained as the desired product in 65% yield, with 10% yield of the ketone byproduct (3a), after 4 h (Table 1, entry 5). To improve the yields of the anthracenes, and minimize byproducts, an attempt was made to enhance the reactivity by adding Brønsted acids. The concurrent use of 1 equiv of methanesulfonic acid (MsOH) or camphorsulfonic acid (CSA) was found to reduce the reactivity, and the use of trifluoromethanesulfonic acid (TfOH) resulted in a complex reaction mixture (Table 1, entries 6–8). However, the concurrent use of trifluoroacetic acid (TFA) increased the yield of 2a to 84% (isolated yield: 79%) after 30 min (Table 1, entry 9). Reducing the amount of TFA to 0.5 equiv led to a decrease in the yield, and the use of TFA without the catalyst Bi(OTf)3 was shown to be inefficient (Table 1, entries 10 and 11).
http://dx.doi.org/10.1016/j.tetlet.2015.10.111 0040-4039/Ó 2015 Published by Elsevier Ltd.
Please cite this article in press as: Park, J.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.111
2
J. Park et al. / Tetrahedron Letters xxx (2015) xxx–xxx Table 2 (continued)
Bi(OTf) 3 (5 mol%)
R2
R2
TFA (1.0 equiv) DCE, 60 o C
R1
R1
Entry
Subtract
Yieldb (%)
Product
Me
Scheme 1. Bi-catalysis of anthracene.
1f
6
2f
Me
Me
70
Me OMe
OMe Table 1 Optimization of the reaction conditionsa
1g
7
2g
Ph
catalyst
Me
+
o
DCE, 60 C
Me
1a
O
1h
8
OMe
OMe F
Catalyst (5 mol %)
1 2 3 4 5 6 7 8 9 10 11
Sc(OTf)3 In(OTf)3 Cu(OTf)2 Fe(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3
2h
61
Me
3a
2a
Entry
86
Acid (equiv)
Time (h)
Yieldb (%) [2a:3a]
MsOH (1.0) CSA (1.0) TfOH (1.0) TFA (1.0) TFA (0.5) TFA (1.0)
20 20 20 10 4 4 10 0.5 0.5 0.5 2
<1:0 21:3 45:8 46:10 65 (59)c:10 48:32 35:39 0:0 84 (79)c:0 59 (52)c:0 23:0
F 1i
9
2c
48
2j
54
2k
46
2l
60
2m
64
Me 1j
10
F
F Me Cl
Cl 1k
11
Me
The Bold values indicate the best reaction condition. a The reaction conditions: 1-benzyl-2-ethylbenzene (1a, 0.3 mol), DCE (2 mL), under a nitrogen atmosphere. b Yields are based on 2a and determined by crude 1H NMR using dibromomethane as the internal standard. c Isolated yield.
1l
12
Cl
Cl Me 1m
13
Me
Table 2 Bismuth-catalyzed anthracenesa
a Reaction conditions: o-alkynyldiarylmethane (1, 0.3 mmol), Bi(OTf)3 (5 mol %), TFA (1.0 equiv), solvent (2 mL), under a nitrogen atmosphere. b Isolated yield.
cycloisomerization
R2
o-alkynyldiarylmethane
to
Bi(OTf)3 (5 mol%)
1 Subtract
R1
Table 3 Bi-catalysis of anthracene
Ph Me
Me 2
O
Yieldb (%)
Product
1a
1
obtain
R2
TFA (1.0 equiv) DCE, 60 oC, 0.5 h
R1
Entry
of
2a
1b Me
Me
79
F
F
2b
67
Me
2c
Entry
Catalyst
1 2 3 4 5
Bi(OTf)3 Bi(OTf)3 BiCl3 BiCl3
Additive TFA TFA TFA
Time (h)
Yield (%) 3a:2a
14 14 24 24 14
84:13 0:97 98:<2 90:<2 91:<2
The reaction conditions: 1-(2-benzylphenyl)ethanone (3a, 0.3 mmol), DCE (2 mL), under a nitrogen atmosphere. Yields are based on 2a and determined by crude 1H NMR using dibromomethane as the internal standard. c Isolated yield. b
52
Me Me
Me 2a
a
1c
3
DCE, 60 oC
3a
Me
2
Catalyst (5 mol%) Additive (1.0 equiv)
Me 1d
4
2d
Ph Me
70
Lewis activation Me Me
Me 5
1e
2e Me
O
Brφnsted activation 58
H O
Bi(OTf)3 O CF3
Scheme 2. The synergistic effect between Bi(OTf)3 and TFA.
Please cite this article in press as: Park, J.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.111
3
J. Park et al. / Tetrahedron Letters xxx (2015) xxx–xxx
H Bi(OTf)3
Me
[Bi] TFA
+
2a
Ph Me
1a O 3a
Bi(OTf)3 / TFA
Scheme 3. Proposed mechanism.
After determining the optimal reaction conditions, the reactivity of various substrates was investigated (Table 2). In the absence of substituents on the benzene ring, product 2a was obtained in 79% yield (Table 2, entry 1). Anthracene 2b was obtained in 67% yield from the reaction of 1-benzyl-2-ethynyl-4-methylbenzene (1b), and when fluorine was introduced at the 5-position of the benzene substituent, product 3b was obtained in 52% yield (Table 2, entry 3). By introducing methyl and methoxy functional groups on the phenyl substituent, the corresponding substituted 9-methylanthracenes were obtained in high yields (58–86%) (Table 2, entries 4–8). However, when highly electronegative halides were introduced, slightly lower yields were obtained (46–60%) (Table 2, entries 9–12). Additionally, when 2-(2-ethynylbenzyl)naphthalene (1m) was used as the substrate, a substituted tetracene (2m) was obtained in 64% yield (Table 2, entry 13). However, the reaction did not proceed for internal alkynes in which methyl or phenyl substituents were introduced at the terminal alkyne position. The mechanism of this reaction and the role played by Bi(OTf)3 and Brønsted acids were investigated by reacting the hydration product 1-(2-benzylphenyl)ethanone (3a) under various catalytic conditions (Table 3). When Bi(OTf)3 alone was used, the desired product was obtained in 13% yield after 14 h, with 84% of the substrate left unreacted (Table 3, entry 1). However, when Bi(OTf)3 and TFA were used concurrently, product 3a was obtained in 97% yield (Table 3, entry 2). In order to determine the effect of the catalyst ligand on this reaction, a comparison was performed with the use of BiCl3 alone and concurrent use of BiCl3 and TFA, neither of which resulted in efficient production of 3a (Table 3, entries 3 and 4). Poor reactivity was also observed when TFA alone was used (Table 3, entry 5). From the results of this experimental study, the role played by TFA in this reaction is attributed to the synergetic effect of double activation of the carbonyl group in the substrate by the Lewis and Brønsted acids, rather than an increase in catalytic reactivity (Scheme 2). In order to determine the effect of Brønsted acids, the reaction was performed in the presence of the proton scavenger 2,6-di-tert-butylpyridine. The reaction did not proceed under these conditions. The proposed mechanism for this reaction is shown in Scheme 3. Bi(OTf)3 mediates the p-activation of the C–C triple bond, thus generating a vinylbismuth intermediate via intramolecular hydroarylation, and finally yields anthracene 2a via isomerization. Additionally, the hydration compound (3a) obtained as a byproduct is proposed to form anthracene 2a as a cyclodehydration product following double activation by Bi(OTf)3 and TFA. In this study, we developed a novel method for synthesizing anthracene derivatives as intramolecular hydroarylation products via Bi(OTf)3-catalyzed alkyne activation. The yield of this reaction could be enhanced by the addition of TFA, which facilitated cyclodehydration of the hydration byproducts generated during
the reaction. The advantages of this reaction include the use of an ecofriendly bismuth catalyst, mild reaction conditions, rapid reaction times, and good yields. Acknowledgments This work was supported by the Human Resource Training Program for Regional Innovation and Creativity through the Ministry of Education and National Research Foundation of Korea (No. 2015H1C1A1035955). Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.10. 111. References and notes 1. (a) Bouas-Laurent, H.; Castellan, A.; Desvergne, J.-P.; Lapouyade, R. Chem. Soc. Rev. 2000, 29, 43; (b) Katz, H. E.; Bao, Z.; Gilat, S. L. Acc. Chem. Res. 2001, 34, 359; (c) Ling, M. M.; Bao, Z. Chem. Mater. 2004, 16, 4824; (d) Harvey, R. G. Curr. Org. Chem. 2004, 8, 303; (e) Wu, J.; Psula, W.; Müllen, K. Chem. Rev. 2007, 107, 718; (f) Anthony, J. E. Angew. Chem., Int. Ed. 2008, 47, 452. 2. (a) Tan, W. B.; Bhambhani, A.; Duff, M. R.; Rodger, A.; Kumar, V. C. Photochem. Photobiol. 2006, 82, 20; (b) Piao, W. H.; Wong, R.; Bai, X. F.; Huang, J.; Campagnolo, D. I.; Dorr, R. T.; Vollmer, T. L.; Shi, F. D. J. Immunol. 2007, 179, 7415; (c) Srinivasan, R.; Tan, L. P.; Wu, H.; Yao, S. Q. Org. Lett. 2008, 10, 2295. 3. (a) Gimenez, R.; Pinol, M.; Serrano, J. L. Chem. Mater. 2004, 16, 1377; (b) Ando, S.; Nishida, J.-I.; Fujiwara, E.; Tada, H.; Inoue, Y.; Tokito, S.; Yamashita, Y. Chem. Mater. 2005, 17, 1261; (c) Hirose, K.; Shiba, Y.; Ishibashi, K.; Doi, Y.; Tobe, Y. Chem. Eur. J. 2008, 14, 981. 4. (a) Hargreaves, J. S.; Webber, S. E. Macromolecules 1984, 17, 235; (b) Rameshbabu, K.; Kim, Y.; Kwon, T.; Yoo, J.; Kim, E. Tetrahedron Lett. 2007, 48, 4755; (c) Morisaki, Y.; Sawamura, T.; Murakami, T.; Chujo, Y. Org. Lett. 2010, 12, 3188. 5. (a) Bradsher, C. K. J. Am. Chem. Soc. 1940, 62, 486; (b) Bradsher, C. K. Chem. Rev. 1946, 38, 447; (c) Vingiello, F. A.; Borkovec, A. J. Am. Chem. Soc. 1956, 78, 3205; (d) Vingiello, F. A.; Henson, P. D. J. Org. Chem. 1965, 30, 2842; (e) Ahmed, M.; Ashby, J.; Ayad, M.; Meth-Cohn, O. J. Chem. Soc., Perkin Trans. 1 1973, 1099; (f) Bradsher, C. K. Chem. Rev. 1987, 87, 1277; (g) Yamato, T.; Sakaue, N.; Shinoda, N.; Matsuo, K. J. Chem. Soc., Perkin Trans. 1 1997, 1193. 6. Shu, C.; Chen, C.-B.; Chen, W.-X.; Ye, L.-W. Org. Lett. 2013, 15, 5542. 7. (a) Kim, C.-E.; Ryu, T.; Kim, S.; Lee, K.; Lee, C.-H. Adv. Synth. Catal. 2013, 355, 2873; (b) Eom, D.; Park, S.; Park, Y.; Lee, K.; Hong, G.; Lee, P. H. Eur. J. Org. Chem. 2013, 2672; (c) Park, C.; Lee, P. H. Org. Lett. 2008, 10, 3359; (d) Mo, J.; Lee, P. H. Org. Lett. 2010, 12, 2570; (e) Mo, J.; Eom, D.; Lee, E.; Lee, P. H. Org. Lett. 2012, 14, 3684; (f) Eom, D.; Park, S.; Park, Y.; Ryu, T.; Lee, P. H. Org. Lett. 2012, 14, 5392; (g) Kang, D.; Kim, J.; Oh, S.; Lee, P. H. Org. Lett. 2012, 14, 5636; (h) Eom, D.; Mo, J.; Lee, P. H.; Gao, Z.; Kim, S. Eur. J. Org. Chem. 2013, 533; (i) Mo, J.; Choi, W.; Min, J.; Kim, C.-E.; Eom, D.; Kim, S. H.; Lee, P. H. J. Org. Chem. 2014, 78, 11382; (j) Kim, H.; Lee, K.; Kim, S.; Lee, P. H. Chem. Commun. 2010, 6341. 8. (a) Park, J.; Yeon, J.; Lee, P. H.; Lee, K. Tetrahedron Lett. 2013, 54, 4414; (b) Yun, J.; Park, J.; Kim, J.; Lee, K. Tetrahedron Lett. 2015, 56, 1045; (c) Chan, L. Y.; Kim, S.; Park, Y.; Lee, P. H. J. Org. Chem. 2012, 77, 5239. 9. (a) Roux, C. L.; Dubac, J. Synlett 2002, 181; (b) Gaspard-Iloughmane, H.; Roux, C. L. Eur. J. Org. Chem. 2004, 2517; (c) Bothwell, J. M. Chem. Soc. Rev. 2011, 40, 4649; (d) Ollevier, T. Org. Biomol. Chem. 2013, 11, 2740.
Please cite this article in press as: Park, J.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.111
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Bismuth-catalyzed synthesis of anthracenes via cycloisomerization of o-alkynyldiarylmethane Jungmin Park a, Hyuck Choi a, Deug-Chan Lee b,c,⇑, Kooyeon Lee a,b,⇑ a
Department of Bio-Health Technology, Kangwon National University, Chuncheon 200-701, Republic of Korea Department of Medical Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea c Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea b
a r t i c l e
i n f o
Article history: Received 14 March 2015 Revised 26 October 2015 Accepted 30 October 2015 Available online xxxx
a b s t r a c t In this study, anthracenes were efficiently synthesized from o-alkynyldiarylmethane using a novel method that exploits the synergistic effect between Bi(OTf)3 as the catalyst, and trifluoroacetic acid (TFA). Through this reaction, we achieved the rapid and efficient synthesis of anthracenes bearing various functional groups under mild conditions. Ó 2015 Published by Elsevier Ltd.
Keywords: Anthracene Hydroarylation Bismuth Brønsted acid Catalysis
Polycyclic aromatic hydrocarbons (PAHs) are important compounds that have been attracting increasing attention in the material sciences for their wide range of applications, such as in photoelectronic devices.1 Anthracene derivatives have also been extensively studied as promising therapeutic agents,2 optical devices,3 and polymers.4 Anthracene compounds are commonly synthesized via a Bradsher-type reaction using 2-acyldiarylmethane in the presence of a Lewis acid.5 However, this reaction has disadvantages, including vigorous reaction conditions, low reaction yields, and a limited range of compatible functional groups. An effective method for the Au-catalyzed synthesis of anthracene derivatives via cycloisomerization of o-alkynyldiarylmethane has recently been reported.6 The disadvantage of this method is the use of an expensive gold catalyst and acid. Recently, a wide range of hydroarylations using Brønsted acid, Au-catalyst, etc. has been reported.7 We also reported that Fe or Bi can be used as an effective catalyst for alkyne activation.8 In particular, Bi has been widely used over the past several years in low-cost, lowtoxicity, and ecofriendly catalysts for organic synthesis.9 This Letter presents a novel method for efficiently synthesizing anthracene derivatives via Bi-catalyzed alkyne activation (Scheme 1). ⇑ Corresponding author. Tel.: +82 33 250 6488; fax: +82 33 250 6480 (D.-C.L.); tel.: +82 33 250 6477; fax: +82 33 250 6470 (K.L.). E-mail addresses: [email protected] (D.-C. Lee), [email protected] (K. Lee).
The reaction conditions were optimized using 1-benzyl-2ethynylbenzene (1a) as a model substrate (Table 1). The catalytic activities of various metal triflates (5 mol %) were investigated by starting material 1a at 60 °C using 1,2-dichloroethane as the solvent. The reaction of 1a did not proceed significantly with Sc (OTf)3 (Table 1, entry 1). The use of indium, copper, and iron catalysts resulted in the generation of the desired product (2a) with yields of 21%, 45%, and 46%, respectively. These low yields were verified by 1H NMR (Table 1, entries 2–4), and the hydration product 1-(2-benzylphenyl)ethanone (3a) was confirmed to be generated as a byproduct. When Bi(OTf)3 was used as the catalyst, 9-methylanthracene (2a) was obtained as the desired product in 65% yield, with 10% yield of the ketone byproduct (3a), after 4 h (Table 1, entry 5). To improve the yields of the anthracenes, and minimize byproducts, an attempt was made to enhance the reactivity by adding Brønsted acids. The concurrent use of 1 equiv of methanesulfonic acid (MsOH) or camphorsulfonic acid (CSA) was found to reduce the reactivity, and the use of trifluoromethanesulfonic acid (TfOH) resulted in a complex reaction mixture (Table 1, entries 6–8). However, the concurrent use of trifluoroacetic acid (TFA) increased the yield of 2a to 84% (isolated yield: 79%) after 30 min (Table 1, entry 9). Reducing the amount of TFA to 0.5 equiv led to a decrease in the yield, and the use of TFA without the catalyst Bi(OTf)3 was shown to be inefficient (Table 1, entries 10 and 11).
http://dx.doi.org/10.1016/j.tetlet.2015.10.111 0040-4039/Ó 2015 Published by Elsevier Ltd.
Please cite this article in press as: Park, J.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.111
2
J. Park et al. / Tetrahedron Letters xxx (2015) xxx–xxx Table 2 (continued)
Bi(OTf) 3 (5 mol%)
R2
R2
TFA (1.0 equiv) DCE, 60 o C
R1
R1
Entry
Subtract
Yieldb (%)
Product
Me
Scheme 1. Bi-catalysis of anthracene.
1f
6
2f
Me
Me
70
Me OMe
OMe Table 1 Optimization of the reaction conditionsa
1g
7
2g
Ph
catalyst
Me
+
o
DCE, 60 C
Me
1a
O
1h
8
OMe
OMe F
Catalyst (5 mol %)
1 2 3 4 5 6 7 8 9 10 11
Sc(OTf)3 In(OTf)3 Cu(OTf)2 Fe(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3 Bi(OTf)3
2h
61
Me
3a
2a
Entry
86
Acid (equiv)
Time (h)
Yieldb (%) [2a:3a]
MsOH (1.0) CSA (1.0) TfOH (1.0) TFA (1.0) TFA (0.5) TFA (1.0)
20 20 20 10 4 4 10 0.5 0.5 0.5 2
<1:0 21:3 45:8 46:10 65 (59)c:10 48:32 35:39 0:0 84 (79)c:0 59 (52)c:0 23:0
F 1i
9
2c
48
2j
54
2k
46
2l
60
2m
64
Me 1j
10
F
F Me Cl
Cl 1k
11
Me
The Bold values indicate the best reaction condition. a The reaction conditions: 1-benzyl-2-ethylbenzene (1a, 0.3 mol), DCE (2 mL), under a nitrogen atmosphere. b Yields are based on 2a and determined by crude 1H NMR using dibromomethane as the internal standard. c Isolated yield.
1l
12
Cl
Cl Me 1m
13
Me
Table 2 Bismuth-catalyzed anthracenesa
a Reaction conditions: o-alkynyldiarylmethane (1, 0.3 mmol), Bi(OTf)3 (5 mol %), TFA (1.0 equiv), solvent (2 mL), under a nitrogen atmosphere. b Isolated yield.
cycloisomerization
R2
o-alkynyldiarylmethane
to
Bi(OTf)3 (5 mol%)
1 Subtract
R1
Table 3 Bi-catalysis of anthracene
Ph Me
Me 2
O
Yieldb (%)
Product
1a
1
obtain
R2
TFA (1.0 equiv) DCE, 60 oC, 0.5 h
R1
Entry
of
2a
1b Me
Me
79
F
F
2b
67
Me
2c
Entry
Catalyst
1 2 3 4 5
Bi(OTf)3 Bi(OTf)3 BiCl3 BiCl3
Additive TFA TFA TFA
Time (h)
Yield (%) 3a:2a
14 14 24 24 14
84:13 0:97 98:<2 90:<2 91:<2
The reaction conditions: 1-(2-benzylphenyl)ethanone (3a, 0.3 mmol), DCE (2 mL), under a nitrogen atmosphere. Yields are based on 2a and determined by crude 1H NMR using dibromomethane as the internal standard. c Isolated yield. b
52
Me Me
Me 2a
a
1c
3
DCE, 60 oC
3a
Me
2
Catalyst (5 mol%) Additive (1.0 equiv)
Me 1d
4
2d
Ph Me
70
Lewis activation Me Me
Me 5
1e
2e Me
O
Brφnsted activation 58
H O
Bi(OTf)3 O CF3
Scheme 2. The synergistic effect between Bi(OTf)3 and TFA.
Please cite this article in press as: Park, J.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.111
3
J. Park et al. / Tetrahedron Letters xxx (2015) xxx–xxx
H Bi(OTf)3
Me
[Bi] TFA
+
2a
Ph Me
1a O 3a
Bi(OTf)3 / TFA
Scheme 3. Proposed mechanism.
After determining the optimal reaction conditions, the reactivity of various substrates was investigated (Table 2). In the absence of substituents on the benzene ring, product 2a was obtained in 79% yield (Table 2, entry 1). Anthracene 2b was obtained in 67% yield from the reaction of 1-benzyl-2-ethynyl-4-methylbenzene (1b), and when fluorine was introduced at the 5-position of the benzene substituent, product 3b was obtained in 52% yield (Table 2, entry 3). By introducing methyl and methoxy functional groups on the phenyl substituent, the corresponding substituted 9-methylanthracenes were obtained in high yields (58–86%) (Table 2, entries 4–8). However, when highly electronegative halides were introduced, slightly lower yields were obtained (46–60%) (Table 2, entries 9–12). Additionally, when 2-(2-ethynylbenzyl)naphthalene (1m) was used as the substrate, a substituted tetracene (2m) was obtained in 64% yield (Table 2, entry 13). However, the reaction did not proceed for internal alkynes in which methyl or phenyl substituents were introduced at the terminal alkyne position. The mechanism of this reaction and the role played by Bi(OTf)3 and Brønsted acids were investigated by reacting the hydration product 1-(2-benzylphenyl)ethanone (3a) under various catalytic conditions (Table 3). When Bi(OTf)3 alone was used, the desired product was obtained in 13% yield after 14 h, with 84% of the substrate left unreacted (Table 3, entry 1). However, when Bi(OTf)3 and TFA were used concurrently, product 3a was obtained in 97% yield (Table 3, entry 2). In order to determine the effect of the catalyst ligand on this reaction, a comparison was performed with the use of BiCl3 alone and concurrent use of BiCl3 and TFA, neither of which resulted in efficient production of 3a (Table 3, entries 3 and 4). Poor reactivity was also observed when TFA alone was used (Table 3, entry 5). From the results of this experimental study, the role played by TFA in this reaction is attributed to the synergetic effect of double activation of the carbonyl group in the substrate by the Lewis and Brønsted acids, rather than an increase in catalytic reactivity (Scheme 2). In order to determine the effect of Brønsted acids, the reaction was performed in the presence of the proton scavenger 2,6-di-tert-butylpyridine. The reaction did not proceed under these conditions. The proposed mechanism for this reaction is shown in Scheme 3. Bi(OTf)3 mediates the p-activation of the C–C triple bond, thus generating a vinylbismuth intermediate via intramolecular hydroarylation, and finally yields anthracene 2a via isomerization. Additionally, the hydration compound (3a) obtained as a byproduct is proposed to form anthracene 2a as a cyclodehydration product following double activation by Bi(OTf)3 and TFA. In this study, we developed a novel method for synthesizing anthracene derivatives as intramolecular hydroarylation products via Bi(OTf)3-catalyzed alkyne activation. The yield of this reaction could be enhanced by the addition of TFA, which facilitated cyclodehydration of the hydration byproducts generated during
the reaction. The advantages of this reaction include the use of an ecofriendly bismuth catalyst, mild reaction conditions, rapid reaction times, and good yields. Acknowledgments This work was supported by the Human Resource Training Program for Regional Innovation and Creativity through the Ministry of Education and National Research Foundation of Korea (No. 2015H1C1A1035955). Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.10. 111. References and notes 1. (a) Bouas-Laurent, H.; Castellan, A.; Desvergne, J.-P.; Lapouyade, R. Chem. Soc. Rev. 2000, 29, 43; (b) Katz, H. E.; Bao, Z.; Gilat, S. L. Acc. Chem. Res. 2001, 34, 359; (c) Ling, M. M.; Bao, Z. Chem. Mater. 2004, 16, 4824; (d) Harvey, R. G. Curr. Org. Chem. 2004, 8, 303; (e) Wu, J.; Psula, W.; Müllen, K. Chem. Rev. 2007, 107, 718; (f) Anthony, J. E. Angew. Chem., Int. Ed. 2008, 47, 452. 2. (a) Tan, W. B.; Bhambhani, A.; Duff, M. R.; Rodger, A.; Kumar, V. C. Photochem. Photobiol. 2006, 82, 20; (b) Piao, W. H.; Wong, R.; Bai, X. F.; Huang, J.; Campagnolo, D. I.; Dorr, R. T.; Vollmer, T. L.; Shi, F. D. J. Immunol. 2007, 179, 7415; (c) Srinivasan, R.; Tan, L. P.; Wu, H.; Yao, S. Q. Org. Lett. 2008, 10, 2295. 3. (a) Gimenez, R.; Pinol, M.; Serrano, J. L. Chem. Mater. 2004, 16, 1377; (b) Ando, S.; Nishida, J.-I.; Fujiwara, E.; Tada, H.; Inoue, Y.; Tokito, S.; Yamashita, Y. Chem. Mater. 2005, 17, 1261; (c) Hirose, K.; Shiba, Y.; Ishibashi, K.; Doi, Y.; Tobe, Y. Chem. Eur. J. 2008, 14, 981. 4. (a) Hargreaves, J. S.; Webber, S. E. Macromolecules 1984, 17, 235; (b) Rameshbabu, K.; Kim, Y.; Kwon, T.; Yoo, J.; Kim, E. Tetrahedron Lett. 2007, 48, 4755; (c) Morisaki, Y.; Sawamura, T.; Murakami, T.; Chujo, Y. Org. Lett. 2010, 12, 3188. 5. (a) Bradsher, C. K. J. Am. Chem. Soc. 1940, 62, 486; (b) Bradsher, C. K. Chem. Rev. 1946, 38, 447; (c) Vingiello, F. A.; Borkovec, A. J. Am. Chem. Soc. 1956, 78, 3205; (d) Vingiello, F. A.; Henson, P. D. J. Org. Chem. 1965, 30, 2842; (e) Ahmed, M.; Ashby, J.; Ayad, M.; Meth-Cohn, O. J. Chem. Soc., Perkin Trans. 1 1973, 1099; (f) Bradsher, C. K. Chem. Rev. 1987, 87, 1277; (g) Yamato, T.; Sakaue, N.; Shinoda, N.; Matsuo, K. J. Chem. Soc., Perkin Trans. 1 1997, 1193. 6. Shu, C.; Chen, C.-B.; Chen, W.-X.; Ye, L.-W. Org. Lett. 2013, 15, 5542. 7. (a) Kim, C.-E.; Ryu, T.; Kim, S.; Lee, K.; Lee, C.-H. Adv. Synth. Catal. 2013, 355, 2873; (b) Eom, D.; Park, S.; Park, Y.; Lee, K.; Hong, G.; Lee, P. H. Eur. J. Org. Chem. 2013, 2672; (c) Park, C.; Lee, P. H. Org. Lett. 2008, 10, 3359; (d) Mo, J.; Lee, P. H. Org. Lett. 2010, 12, 2570; (e) Mo, J.; Eom, D.; Lee, E.; Lee, P. H. Org. Lett. 2012, 14, 3684; (f) Eom, D.; Park, S.; Park, Y.; Ryu, T.; Lee, P. H. Org. Lett. 2012, 14, 5392; (g) Kang, D.; Kim, J.; Oh, S.; Lee, P. H. Org. Lett. 2012, 14, 5636; (h) Eom, D.; Mo, J.; Lee, P. H.; Gao, Z.; Kim, S. Eur. J. Org. Chem. 2013, 533; (i) Mo, J.; Choi, W.; Min, J.; Kim, C.-E.; Eom, D.; Kim, S. H.; Lee, P. H. J. Org. Chem. 2014, 78, 11382; (j) Kim, H.; Lee, K.; Kim, S.; Lee, P. H. Chem. Commun. 2010, 6341. 8. (a) Park, J.; Yeon, J.; Lee, P. H.; Lee, K. Tetrahedron Lett. 2013, 54, 4414; (b) Yun, J.; Park, J.; Kim, J.; Lee, K. Tetrahedron Lett. 2015, 56, 1045; (c) Chan, L. Y.; Kim, S.; Park, Y.; Lee, P. H. J. Org. Chem. 2012, 77, 5239. 9. (a) Roux, C. L.; Dubac, J. Synlett 2002, 181; (b) Gaspard-Iloughmane, H.; Roux, C. L. Eur. J. Org. Chem. 2004, 2517; (c) Bothwell, J. M. Chem. Soc. Rev. 2011, 40, 4649; (d) Ollevier, T. Org. Biomol. Chem. 2013, 11, 2740.
Please cite this article in press as: Park, J.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.111