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A green protocol for ligand, copper and base free Sonogashira cross-coupling reaction
Tetrahedron Letters 57 (2016) 3760–3763
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
A green protocol for ligand, copper and base free Sonogashira crosscoupling reaction Anindita Dewan ⇑, Manashi Sarmah, Utpal Bora, Ashim J. Thakur Department of Chemical Sciences, Tezpur University, Napaam, Tezpur, Assam 784028, India
a r t i c l e
i n f o
Article history: Received 22 April 2016 Revised 5 July 2016 Accepted 6 July 2016 Available online 7 July 2016 Keywords: Sonogashira coupling Aryl halides Pd(OAc)2 WEB EtOH
a b s t r a c t A convenient methodology has been developed for palladium catalyzed Sonogashira cross-coupling reaction under mild and green reaction conditions. The reaction is catalyzed by an in situ generated catalytic system based on Pd(OAc)2 and WEB (water extract of banana peels ash) in the absence of any organic or inorganic base, ligand and copper salt with excellent yield of cross coupled product. The reaction condition is compatible with electronically diversified aryl iodides and electronically diversified aryl or aliphatic alkyne. The present method developed for the Sonogashira reaction offers many advantages including high conversion, high economy, the involvement of non-toxic green substrates, etc. Ó 2016 Elsevier Ltd. All rights reserved.
Introduction The Pd-catalyzed Sonogashira cross-coupling reaction of terminal alkynes with aryl halides is one of the most reliable tools for the synthesis of polyfunctional alkynes, which finds extensive applications in pharmaceuticals,1 dyes,2 sensors,3 electronics,4 polymers,5 guest–host constructs,6 natural products,7 and heterocycle synthesis.8 Initially, this reaction was performed in the presence of a Pd salt as a catalyst, a Cu-salt as a co-catalyst, a ligand and in organic solvents using excess amount of an amine as a co-solvent.9 Although, addition of copper is advantageous in terms of reaction efficiency, however, formation of an undesired alkyne homocoupling product from Cu-mediated reactions enforces the researchers to develop a Cu free protocol for the Sonogashira cross-coupling reaction.10 As a result, several alternative protocols have been developed where, the use of other additives such as Ag,11 Zn,12 Sn,13 and salts10a,c,14 as activators has been reported. It has been observed that ligand plays a key role in the Pdcatalyzed Sonogashira reaction which is generally used to stabilize the active Pd species during the course of the reaction. Among different ligands designed, noticeable success have been achieved with phosphine based ligands such as electron rich bulky phosphanes,15 water soluble phosphanes such as TPPTS and TXPTS,16 nitrogen based ligands such as N-heterocyclic carbenes,17 oxime palladacycles,18 amines,19 and Salen.20 However, in ⇑ Corresponding author. Tel.: +91 3712275067; fax: +91 (3712) 267005/6. E-mail address: [email protected] (A. Dewan). http://dx.doi.org/10.1016/j.tetlet.2016.07.021 0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
majority of cases, associated principal drawbacks are the availability, stability, and cost of the Pd complexes and related ligands and their moisture sensitivity. In addition, the insolubility of most of the ligands and substrates in pure water serves a significant limitation for Sonogashira cross-coupling reaction. Consequently, very few reports are available where water is used as the solvent media.21 From the concept of green chemistry; it is the necessity to develop reaction methodologies in aqueous media under mild reaction conditions using cheap and nontoxic reagents preferably using natural feedstock. However, in most of the catalytic processes, organic solvents are usually employed as the reaction media, often creating a great deal of safety, health and environmental issues due to their flammability and toxicity. Because of the increasing concern regarding environmental impact, there has been a continuous effort to develop alternative processes that minimizes pollution in the chemical synthesis. Use of environmentally benign solvents, biodegradable and nontoxic chemicals has become one of the most exciting research endeavors for organic chemists in order to prepare new biologically active molecules. Recently, on complying with the greener perspectives, Suzuki– Miyaura cross-coupling reaction has been carried out using Pd (OAc)2 in WEB22 (water extract of banana peels ash) and WERSA23 (water extract of rice straw ash). WEB–H2O2 system is also found to be effective for Dakin reaction.24 The chemical and analytical analyses of WEB and WERSA have indicated their basic nature. It has been well documented in literature that the base plays a significant role in Sonogashira reaction. Thus, the feasibility of using inherent basicity, WEB/WERSA in Pd-catalyzed Sonogashira
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reaction deserves serious attention. The innocuous nature and rate enhancing effect of such natural ‘feedstocks’ in chemical synthesis as an alternative to hazardous organic solvents or other toxic chemicals are widely recognized for the development of greener processes. On the other hand, WEB is an agro waste of banana tree. So, there is no doubt that WEB promises great potential in green chemical processes from the economic and environmental points of view. In this communication, we wish to report the successful utilization of WEB in Pd catalyzed ligand and base free Sonogashira reaction. The chemical contents of banana peels as mentioned in the literature reveal the presence of potassium, sodium, carbonate and chloride along with a host of other elements.22 In our case, the distribution of elements and their concentration in WEB was analyzed by Ion Chromatography (Supplementary information) suggesting the presence of K, Na, Mg and Ca. Initially, we have examined the efficiency of WEB as solvent in Sonogashira reaction using Pd(OAc)2 as the catalyst by taking 4iodo-nitrobenzene and phenylacetylene as the model substrates in the absence of base, ligand or any other additive. In this initial experiment, we were able to isolate 50% of cross-coupling product at room temperature (Table 1, entry 1). The lower yield of the cross coupled product may be due to the poor solubility of 4-iodonitrobenzene and phenylacetylene in water. It is a well known fact that the insolubility of most of the reactants in water restricts their use in water as a solvent for Sonogashira reaction. Therefore, we have carried the reaction using WEB and CH3CN as co-solvent (1:1) ratio. However, addition of CH3CN did not improve the yield of the product. Moreover, use of other solvents such as THF, dioxane, toluene, or DMF as co-solvent did not show any positive impact. On the other hand, use of ethanol (2 mL) as a co-solvent with WEB (4 mL) significantly improved the yield of the desired product to about 70% (Table 1, entry 2). It has been observed that the WEB/ethanol ratio is very important and we have obtained excellent yield of cross-coupling product using WEB (4 mL) and ethanol (4 mL) (Table 1, entry 2 vs 3). Moreover, several test reactions were carried out using different amounts of WEB/ethanol in 1:1 ratio, and observed that amount of WEB/ethanol also has a significant effect on the reaction rate (Table 1, entries 2 vs 5 & 6). The best result with 98% cross-coupling product was obtained with ethanol/WEB ratio 4:4 (Table 1, entry 3). Interestingly, iso-propanol also afforded comparable yield of the cross-coupling product (Table 1, entry 4). However, the coupling reaction did not proceed
Table 1 Optimization of Pd(OAc)2 and solvent in Sonogashira cross-coupling reactiona I
Pd(OAc) 2
O 2N
WEB, rt
O 2N
Entry
Catalyst (mol %)
Co-solvent (mL)
WEB (mL)
Time (h)
Yiedc (%)
1 2 3 4 5 6 7 8 9 10b 11
Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) PdCl2 (1) Pd(OAc)2(0.5) Pd(OAc)2 (1) —
— EtOH (2) EtOH (4) i-PrOH (4) EtOH (2) EtOH (3) EtOH (4) EtOH (4) EtOH (4) EtOH (4) EtOH (4)
4 4 4 4 2 3 — 4 4 4 4
24 24 10 10 10 10 24 10 12 4 24
50 70 98 95 50 85 0 95 70 98 0
a Reaction conditions: 4-nitro-iodobenzene (1 mmol), Pd(OAc)2, WEB, EtOH. b Reaction was carried out at 60 °C. c Isolated yields.
(0.5 mmol),
phenylacetylene
in the absence of WEB under the present reaction conditions (Table 1, entry 7). The main objectives of this protocol is to develop an in-situ generated catalytic system based on Pd(OAc)2 and WEB for Sonogashira reaction under an air atmosphere at room temperature. Literature reports reveal that in many Pd(II) salt-catalyzed reactions, Pd(II) species are reduced to Pd(0) species at the end of each reaction cycle.25 Consequently, to make the reaction catalytic with respect to Pd(II), the presence of an oxidant such as copper salts, manganese salts, benzoquinone, and tert-butylhydroperoxide (TBHP) are required to allow for the conversion of Pd(0) into Pd(II) in-situ.25 Under the present reaction conditions, it is believed that the presence of transition metal salts has played an important role for the conversion of Pd(0) into Pd(II) in-situ and significantly enhances the reaction yields.21,24 Again, it is also believed that carbonates of sodium and potassium of banana peels act as base here and chlorides of sodium and copper act as promoters for Sonogashira reactions.22 It was clear that WEB with other Pd (II) salts such as PdCl2 also exhibited a high catalytic activity (Table 1, entry 8). But, in the absence of Pd(OAc)2, the reaction did not proceed at all under the same reaction conditions (Table 1, entry 11). To optimize the reaction conditions, the effect of the amount of Pd(OAc)2 on the coupling reaction was studied (Table 1, entries 3 and 9). From the results (Table 1), we can see that an excellent yield of the desired product was obtained in the presence of 1 mol % Pd(OAc)2. Decreasing the catalyst loading to 0.5 mol % was found to be sufficient to give a moderate conversion with 70% isolated yield of the product (Table 1, entry 9). We further wished to investigate the effect of temperature in Sonogashira cross-coupling reaction. It was clear that reaction rate was enhanced by increasing the temperature to 60 °C and reaction was completed within 4 h (Table 1, on comparing entry 3 vs 10). So, it is important to mention that Pd(OAc)2 in WEB catalyzed Sonogashira cross-coupling reaction is very efficient with excellent yields at 60 °C under mild reaction conditions. We also investigated the substrate ratio for efficient coupling. The favorable conditions were observed with 1:1.5 equiv of iodobenzene to phenylacetylene (Table 2, entries 2 vs 1 vs 3). The scope and limitation of the current protocol has been investigated with several electronically diverse aryl iodides and acetylene under optimized greener reaction condition.26 The results are summarized in Table 3. It was noticed that the aryl halides with electron-withdrawing substituents, like nitro group (Table 3, entry 2) afforded the corresponding coupled products in excellent yields. No significant differences were observed in the yield with meta substituted electron rich aryl iodide (Table 3, entry 3). But, in case of orthonitroiodobenzene product yield was very low (Table 3, entry 4). In general, ortho substituted aryl iodides required more reaction time as compared to the para substituted counterparts owing to steric hindrance put by ortho substituents. It is important to mention that, generally, aryl halides with electron-withdrawing groups
Table 2 Optimization of substrate ratioa I
Pd(OAc) 2 (1 mol%) WEB:EtOH, 60 0 C
O 2N
O 2N
Entry
A:B (mmol)
Time (h)
Yieldb (%)
1 2 3
1:1 1:1.5 1:2
8 4 4
70 98 98
a Reaction conditions: 4-nitro-iodobenzene (A mmol), phenylacetylene (B mmol), Pd(OAc)2 (1 mol %), WEB (4 mL), EtOH (4 mL). b Isolated yields.
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Table 3 Pd(OAc)2 and WEB/EtOH catalyzed Sonogashira cross-coupling reaction of aryl halides with acetylenea
X R
R2
1
R1
Pd(OAc)2 (1 mol%)
R2
WEB:EtOH (1:1) 60oC
Entry
R1
R2
X
Time (h)
Yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
H 4-NO2 3-NO2 2-NO2 4-CH3 3-CH3 4-CH3 4-OCH3 4-NH2 H 4-CH3 3-CH3 H 4-CH3 H 4-CH3 H 4-CH3 4-CH3 4-NO2
C6H5 C6H5 C6H5 C6H5 C6H5 C6H5 4-CH3 C6H4 C6H5 C6H5 Butyl Butyl Butyl Cyclohexyl Cyclohexyl decyl decyl C6H5 C6H5 4-CH3 C6H4 C6H5
I I I I I I I I I I I I I I I I Br Br Br Br
5 4 8 8 1 8 2 8 8 4 8 8 5 8 8 8 8 8 8 8
98 98 85 40 98 90 96 75 50 95 85 60 90 70 80 60 95 95 85 50
a
Reaction conditions: Arylhalide (1 mmol), phenylacetylene (1.5 mmol), Pd (OAc)2 (1 mol %), WEB (4 mL), EtOH (4 mL). b Isolated yields.
at the para position are much more reactive than aryl halides bearing electron donating groups. Thus, to investigate the effects of the new catalytic system with an electron-donating substrate, we performed the reaction between 4-iodotoluene and phenylacetylene under similar reaction conditions. It is surprising to see that 4iodotoluene gave superior product formation compared to 4iodonitrobenzene within shorter reaction time (Table 3, entry 5). The reaction also proceeds well in case of meta substituted iodotoluene (Table 3, entry 6). No significant differences were observed in the yield when phenyl acetylene was replaced by p-tolylphenylacetylene (Table 3, entry 7). However, the reaction of aryl halides with electron-donating groups, such as methoxy and amine gave the coupling products with slightly lower yields (Table 3, entries 8 and 9). Next, we examine the catalytic system for electronically diverse aryl acetylenes with aliphatic alkynes (Table 3, entries 10–16). In all cases, modest to good yield of desired cross-coupling products were observed. However, iodobenzene gave superior product formation with aliphatic alkynes (Table 3, entries 10, 13 & 15). Our next endeavor was to extend the scope of this greener protocol for coupling of aryl bromides with acetylene. We observed low conversion at room temperature for arylbromides. Hence, next we perform this reaction at 60 °C by taking the same catalyst loading. Aryl bromide having electron donating substituent viz. 4-CH3 rendered good yields of isolated cross-coupling products (Table 3, entries 18 and 19). However, the reaction of aryl bromide containing electron withdrawing substituents such as p-bromonitrobenzene with phenylacetylene did not proceed well and gave only 50% (Table 3, entry 20) conversion. Conclusions In conclusion, we have developed a convenient methodology for palladium catalyzed Sonogashira reaction under ligand and copper free conditions. The reaction is catalyzed by an in-situ generated catalytic system based on Pd(OAc)2 and WEB. The absence of additives, use of ethanol together with WEB as the solvent and the base
and wider substrate scope make it an attractive pathway for Sonogashira coupling reaction. This offers a greener alternative to the existing protocols since the reaction proceeds under ligand and copper free conditions in aqueous medium. Electronically diversified aryl iodides underwent the coupling reaction with electronically diversified aryl or aliphatic alkyne in excellent yields. The present method developed for the Sonogashira reaction offers many advantages including high conversion, high economy, the involvement of non-toxic green substrates, etc. Acknowledgments Authors are thankful to U.G.C, New Delhi for awarding Dr. D. S. Kothari Postdoctoral Fellowship to Dr. A. Dewan. M. S. thanks Tezpur University for providing institutional fellowship. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.07. 021. References and notes 1. (a) Sonogashira, K. In Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, I. E., Ed.; Wiley-VCH: Weinheim, Germany, 2002; Vol. 1, pp 493–529; (b) Marsden, A. J.; Haley, M. M. In Metal-Catalyzed Cross-Coupling Reactions; de Meijre, A., Diederich, F., Eds., 2nd ed.; Wiley-VCH: Weinheim, Germany, 2004; pp 317–394. 2. (a) Shao, F.; Weissleder, R.; Hilderbrand, S. A. Bioconjug. Chem. 2008, 19, 2487– 2491; (b) Shieh, P.; Bertozzi, C. R. Org. Biomol. Chem. 2014, 12, 9307–9320. 3. (a) Danilkina, N. A.; Vlasov, P. S.; Vodianik, S. M.; Kruchinin, A. A.; Vlasov, Y. G.; Balova, I. A. Beilstein J. Org. Chem. 2015, 11, 373–384; (b) Dai, C.; Cheng, Y.; Cui, J.; Wang, B. Molecules 2010, 15, 5768–5781. 4. (a) Wang, C. S.; Batsanov, A. S.; Bryce, M. R.; Martin, S.; Nichols, R. J.; Higgins, S. J.; Garcia-Suarez, V. M.; Lambert, C. J. J. Am. Chem. Soc. 2009, 131, 15647–15654; (b) Haiss, W.; Wang, C. S.; Grace, I.; Batsanov, A. S.; Schiffrin, D. J.; Higgins, S. J.; Bryce, M. R.; Lambert, C. J.; Nichols, R. J. Nat. Mater. 2006, 5, 995–1002; (c) Kaliginedi, V.; Moreno-Garcia, P.; Valkenier, H.; Hong, W. J.; Garcia-Suarez, V. M.; Buiter, P.; Otten, J. L. H.; Hummelen, J. C.; Lambert, C. J.; Wandlowski, T. J. Am. Chem. Soc. 2012, 134, 5262–5275; (d) Marques-Gonzalez, S.; Yufit, D. S.; Howard, J. A. K.; Martin, S.; Osorio, H. M.; Garcia-Suarez, V. M.; Nichols, R. J.; Higgins, S. J.; Cea, P.; Low, P. J. Dalton Trans. 2013, 42, 338–341; (e) MorenoGarcia, P.; Gulcur, M.; Manrique, D. Z.; Pope, T.; Hong, W.; Kaliginedi, V.; Huang, C.; Batsanov, A. S.; Bryce, M. R.; Lambert, C.; Wandlowski, T. J. Am. Chem. Soc. 2013, 135, 12228–12240; (f) Rigaut, S. Dalton Trans. 2013, 42, 15859– 15863. 5. Long, N. J.; Williams, C. K. Angew. Chem., Int. Ed. 2003, 42, 2586–2617. 6. (a) Huan, X.; Wang, D.; Dong, R.; Tu, C.; Zhu, B.; Yan, D.; Zhu, X. Macromolecules 2012, 45, 5941–5947; (b) Liu, H.; Zhang, Y.; Hu, J.; Li, C.; Liu, S. Macromol. Chem. Phys. 2009, 210, 2125–2137. 7. (a) Reed, M. W.; Moore, H. W. J. Org. Chem. 1988, 53, 4166–4171; (b) Harmrolfs, K.; Mancuso, L.; Drung, B.; Sasse, F.; Kirschning, A. Beilstein J. Org. Chem. 2014, 10, 535–543. 8. (a) Khong, S.; Kwon, O. J. Org. Chem. 2012, 77, 8257–8267; (b) Patil, N. T.; Raut, V. S. J. Org. Chem. 2010, 75, 6961–6964; (c) Sakai, N.; Tamura, K.; Shimamura, K.; Ikeda, R.; Konakahara, T. Org. Lett. 2012, 14, 836–839; (d) Liu, B.; Gao, H.; Yu, Y.; Wu, W.; Jiang, H. J. Org. Chem. 2013, 78, 10319–10328. 9. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467– 4470; (b) Eckhardt, M.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 13642–13643; (c) Mino, T.; Suzuki, S.; Hirai, K.; Sakamoto, M.; Fujita, T. Synlett 2011, 1277–1280. 10. (a) Urgaonkar, S.; Verkade, J. G. J. Org. Chem. 2004, 69, 5752–5755; (b) Lauterbach, T.; Livendahl, M.; Rosellon, A.; Espinet, P.; Echavarren, M. A. Org. Lett. 2010, 12, 3006–3009; (c) Fleckenstein, C. A.; Plenio, H. Green Chem. 2008, 10, 563–570; (d) Liang, Y.; Xie, Y.-X.; Li, J.-H. J. Org. Chem. 2006, 71, 379–381; (e) Yi, C.; Hua, R. J. Org. Chem. 2006, 71, 2535–2537; (f) Neumann, K. T.; Laursen, S. R.; Lindhardt, A. T.; Bang-Andersen, B.; Skrydstrup, T. Org. Lett. 2014, 16, 2216–2219. 11. (a) Mori, A.; Kawashima, J.; Shimada, T.; Suguro, M.; Hirabayashi, K.; Nishihara, Y. Org. Lett. 2000, 2, 2935–2937; (b) Yamamoto, Y. Chem. Rev. 2008, 108, 3199– 3222. 12. Finke, A. D.; Elleby, E. C.; Boyd, M. J.; Weissman, H.; Moore, J. S. J. Org. Chem. 2009, 74, 8897. 13. Negishi, E.-I.; Anastasia, L. Chem. Rev. 2003, 103, 1979–2017. 14. Gogoi, A.; Dewan, A.; Bora, U. RSC Adv. 2015, 5, 16–19. 15. (a) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927–928; (b) Bohm, V. P. W.; Herrmann, A. W. Eur. J. Org. Chem. 2000, 3679–3681; (c) Hundertmark, T.; Littke, A. F.; Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2, 1729–1731; (d)
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22. Boruah, P. R.; Ali, A. A.; Saikia, B.; Sarma, D. Green Chem. 2015, 17, 1442–1445. 23. Boruah, P. R.; Ali, A. A.; Chetia, M.; Saikia, B.; Sarma, D. Chem. Commun. 2015, 11489–11492. 24. Saikia, B.; Borah, P.; Barua, N. C. Green Chem. 2015, 17, 4533–4536. 25. Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873–2920. 26. General experimental procedure for Sonogashira reaction: A mixture of aryl halide (1 mmol), terminal acetylene (1.5 mmol) and Pd(OAc)2 (1 mol %) in WEB/ethanol (1:1, 8 mL) was stirred for the indicated time at 60 °C. After completion of the reaction (vide TLC), the reaction solution was extracted with ethyl acetate (4 10 mL). The products were purified by column chromatography over silica gel using n-hexane/ethyl acetate (9: 1 v/v) to obtain the desired coupling products. The products were characterized by comparing 1H, 13C NMR spectroscopic data and GC–MS data with authentic samples.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
A green protocol for ligand, copper and base free Sonogashira crosscoupling reaction Anindita Dewan ⇑, Manashi Sarmah, Utpal Bora, Ashim J. Thakur Department of Chemical Sciences, Tezpur University, Napaam, Tezpur, Assam 784028, India
a r t i c l e
i n f o
Article history: Received 22 April 2016 Revised 5 July 2016 Accepted 6 July 2016 Available online 7 July 2016 Keywords: Sonogashira coupling Aryl halides Pd(OAc)2 WEB EtOH
a b s t r a c t A convenient methodology has been developed for palladium catalyzed Sonogashira cross-coupling reaction under mild and green reaction conditions. The reaction is catalyzed by an in situ generated catalytic system based on Pd(OAc)2 and WEB (water extract of banana peels ash) in the absence of any organic or inorganic base, ligand and copper salt with excellent yield of cross coupled product. The reaction condition is compatible with electronically diversified aryl iodides and electronically diversified aryl or aliphatic alkyne. The present method developed for the Sonogashira reaction offers many advantages including high conversion, high economy, the involvement of non-toxic green substrates, etc. Ó 2016 Elsevier Ltd. All rights reserved.
Introduction The Pd-catalyzed Sonogashira cross-coupling reaction of terminal alkynes with aryl halides is one of the most reliable tools for the synthesis of polyfunctional alkynes, which finds extensive applications in pharmaceuticals,1 dyes,2 sensors,3 electronics,4 polymers,5 guest–host constructs,6 natural products,7 and heterocycle synthesis.8 Initially, this reaction was performed in the presence of a Pd salt as a catalyst, a Cu-salt as a co-catalyst, a ligand and in organic solvents using excess amount of an amine as a co-solvent.9 Although, addition of copper is advantageous in terms of reaction efficiency, however, formation of an undesired alkyne homocoupling product from Cu-mediated reactions enforces the researchers to develop a Cu free protocol for the Sonogashira cross-coupling reaction.10 As a result, several alternative protocols have been developed where, the use of other additives such as Ag,11 Zn,12 Sn,13 and salts10a,c,14 as activators has been reported. It has been observed that ligand plays a key role in the Pdcatalyzed Sonogashira reaction which is generally used to stabilize the active Pd species during the course of the reaction. Among different ligands designed, noticeable success have been achieved with phosphine based ligands such as electron rich bulky phosphanes,15 water soluble phosphanes such as TPPTS and TXPTS,16 nitrogen based ligands such as N-heterocyclic carbenes,17 oxime palladacycles,18 amines,19 and Salen.20 However, in ⇑ Corresponding author. Tel.: +91 3712275067; fax: +91 (3712) 267005/6. E-mail address: [email protected] (A. Dewan). http://dx.doi.org/10.1016/j.tetlet.2016.07.021 0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
majority of cases, associated principal drawbacks are the availability, stability, and cost of the Pd complexes and related ligands and their moisture sensitivity. In addition, the insolubility of most of the ligands and substrates in pure water serves a significant limitation for Sonogashira cross-coupling reaction. Consequently, very few reports are available where water is used as the solvent media.21 From the concept of green chemistry; it is the necessity to develop reaction methodologies in aqueous media under mild reaction conditions using cheap and nontoxic reagents preferably using natural feedstock. However, in most of the catalytic processes, organic solvents are usually employed as the reaction media, often creating a great deal of safety, health and environmental issues due to their flammability and toxicity. Because of the increasing concern regarding environmental impact, there has been a continuous effort to develop alternative processes that minimizes pollution in the chemical synthesis. Use of environmentally benign solvents, biodegradable and nontoxic chemicals has become one of the most exciting research endeavors for organic chemists in order to prepare new biologically active molecules. Recently, on complying with the greener perspectives, Suzuki– Miyaura cross-coupling reaction has been carried out using Pd (OAc)2 in WEB22 (water extract of banana peels ash) and WERSA23 (water extract of rice straw ash). WEB–H2O2 system is also found to be effective for Dakin reaction.24 The chemical and analytical analyses of WEB and WERSA have indicated their basic nature. It has been well documented in literature that the base plays a significant role in Sonogashira reaction. Thus, the feasibility of using inherent basicity, WEB/WERSA in Pd-catalyzed Sonogashira
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reaction deserves serious attention. The innocuous nature and rate enhancing effect of such natural ‘feedstocks’ in chemical synthesis as an alternative to hazardous organic solvents or other toxic chemicals are widely recognized for the development of greener processes. On the other hand, WEB is an agro waste of banana tree. So, there is no doubt that WEB promises great potential in green chemical processes from the economic and environmental points of view. In this communication, we wish to report the successful utilization of WEB in Pd catalyzed ligand and base free Sonogashira reaction. The chemical contents of banana peels as mentioned in the literature reveal the presence of potassium, sodium, carbonate and chloride along with a host of other elements.22 In our case, the distribution of elements and their concentration in WEB was analyzed by Ion Chromatography (Supplementary information) suggesting the presence of K, Na, Mg and Ca. Initially, we have examined the efficiency of WEB as solvent in Sonogashira reaction using Pd(OAc)2 as the catalyst by taking 4iodo-nitrobenzene and phenylacetylene as the model substrates in the absence of base, ligand or any other additive. In this initial experiment, we were able to isolate 50% of cross-coupling product at room temperature (Table 1, entry 1). The lower yield of the cross coupled product may be due to the poor solubility of 4-iodonitrobenzene and phenylacetylene in water. It is a well known fact that the insolubility of most of the reactants in water restricts their use in water as a solvent for Sonogashira reaction. Therefore, we have carried the reaction using WEB and CH3CN as co-solvent (1:1) ratio. However, addition of CH3CN did not improve the yield of the product. Moreover, use of other solvents such as THF, dioxane, toluene, or DMF as co-solvent did not show any positive impact. On the other hand, use of ethanol (2 mL) as a co-solvent with WEB (4 mL) significantly improved the yield of the desired product to about 70% (Table 1, entry 2). It has been observed that the WEB/ethanol ratio is very important and we have obtained excellent yield of cross-coupling product using WEB (4 mL) and ethanol (4 mL) (Table 1, entry 2 vs 3). Moreover, several test reactions were carried out using different amounts of WEB/ethanol in 1:1 ratio, and observed that amount of WEB/ethanol also has a significant effect on the reaction rate (Table 1, entries 2 vs 5 & 6). The best result with 98% cross-coupling product was obtained with ethanol/WEB ratio 4:4 (Table 1, entry 3). Interestingly, iso-propanol also afforded comparable yield of the cross-coupling product (Table 1, entry 4). However, the coupling reaction did not proceed
Table 1 Optimization of Pd(OAc)2 and solvent in Sonogashira cross-coupling reactiona I
Pd(OAc) 2
O 2N
WEB, rt
O 2N
Entry
Catalyst (mol %)
Co-solvent (mL)
WEB (mL)
Time (h)
Yiedc (%)
1 2 3 4 5 6 7 8 9 10b 11
Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) Pd(OAc)2 (1) PdCl2 (1) Pd(OAc)2(0.5) Pd(OAc)2 (1) —
— EtOH (2) EtOH (4) i-PrOH (4) EtOH (2) EtOH (3) EtOH (4) EtOH (4) EtOH (4) EtOH (4) EtOH (4)
4 4 4 4 2 3 — 4 4 4 4
24 24 10 10 10 10 24 10 12 4 24
50 70 98 95 50 85 0 95 70 98 0
a Reaction conditions: 4-nitro-iodobenzene (1 mmol), Pd(OAc)2, WEB, EtOH. b Reaction was carried out at 60 °C. c Isolated yields.
(0.5 mmol),
phenylacetylene
in the absence of WEB under the present reaction conditions (Table 1, entry 7). The main objectives of this protocol is to develop an in-situ generated catalytic system based on Pd(OAc)2 and WEB for Sonogashira reaction under an air atmosphere at room temperature. Literature reports reveal that in many Pd(II) salt-catalyzed reactions, Pd(II) species are reduced to Pd(0) species at the end of each reaction cycle.25 Consequently, to make the reaction catalytic with respect to Pd(II), the presence of an oxidant such as copper salts, manganese salts, benzoquinone, and tert-butylhydroperoxide (TBHP) are required to allow for the conversion of Pd(0) into Pd(II) in-situ.25 Under the present reaction conditions, it is believed that the presence of transition metal salts has played an important role for the conversion of Pd(0) into Pd(II) in-situ and significantly enhances the reaction yields.21,24 Again, it is also believed that carbonates of sodium and potassium of banana peels act as base here and chlorides of sodium and copper act as promoters for Sonogashira reactions.22 It was clear that WEB with other Pd (II) salts such as PdCl2 also exhibited a high catalytic activity (Table 1, entry 8). But, in the absence of Pd(OAc)2, the reaction did not proceed at all under the same reaction conditions (Table 1, entry 11). To optimize the reaction conditions, the effect of the amount of Pd(OAc)2 on the coupling reaction was studied (Table 1, entries 3 and 9). From the results (Table 1), we can see that an excellent yield of the desired product was obtained in the presence of 1 mol % Pd(OAc)2. Decreasing the catalyst loading to 0.5 mol % was found to be sufficient to give a moderate conversion with 70% isolated yield of the product (Table 1, entry 9). We further wished to investigate the effect of temperature in Sonogashira cross-coupling reaction. It was clear that reaction rate was enhanced by increasing the temperature to 60 °C and reaction was completed within 4 h (Table 1, on comparing entry 3 vs 10). So, it is important to mention that Pd(OAc)2 in WEB catalyzed Sonogashira cross-coupling reaction is very efficient with excellent yields at 60 °C under mild reaction conditions. We also investigated the substrate ratio for efficient coupling. The favorable conditions were observed with 1:1.5 equiv of iodobenzene to phenylacetylene (Table 2, entries 2 vs 1 vs 3). The scope and limitation of the current protocol has been investigated with several electronically diverse aryl iodides and acetylene under optimized greener reaction condition.26 The results are summarized in Table 3. It was noticed that the aryl halides with electron-withdrawing substituents, like nitro group (Table 3, entry 2) afforded the corresponding coupled products in excellent yields. No significant differences were observed in the yield with meta substituted electron rich aryl iodide (Table 3, entry 3). But, in case of orthonitroiodobenzene product yield was very low (Table 3, entry 4). In general, ortho substituted aryl iodides required more reaction time as compared to the para substituted counterparts owing to steric hindrance put by ortho substituents. It is important to mention that, generally, aryl halides with electron-withdrawing groups
Table 2 Optimization of substrate ratioa I
Pd(OAc) 2 (1 mol%) WEB:EtOH, 60 0 C
O 2N
O 2N
Entry
A:B (mmol)
Time (h)
Yieldb (%)
1 2 3
1:1 1:1.5 1:2
8 4 4
70 98 98
a Reaction conditions: 4-nitro-iodobenzene (A mmol), phenylacetylene (B mmol), Pd(OAc)2 (1 mol %), WEB (4 mL), EtOH (4 mL). b Isolated yields.
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Table 3 Pd(OAc)2 and WEB/EtOH catalyzed Sonogashira cross-coupling reaction of aryl halides with acetylenea
X R
R2
1
R1
Pd(OAc)2 (1 mol%)
R2
WEB:EtOH (1:1) 60oC
Entry
R1
R2
X
Time (h)
Yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
H 4-NO2 3-NO2 2-NO2 4-CH3 3-CH3 4-CH3 4-OCH3 4-NH2 H 4-CH3 3-CH3 H 4-CH3 H 4-CH3 H 4-CH3 4-CH3 4-NO2
C6H5 C6H5 C6H5 C6H5 C6H5 C6H5 4-CH3 C6H4 C6H5 C6H5 Butyl Butyl Butyl Cyclohexyl Cyclohexyl decyl decyl C6H5 C6H5 4-CH3 C6H4 C6H5
I I I I I I I I I I I I I I I I Br Br Br Br
5 4 8 8 1 8 2 8 8 4 8 8 5 8 8 8 8 8 8 8
98 98 85 40 98 90 96 75 50 95 85 60 90 70 80 60 95 95 85 50
a
Reaction conditions: Arylhalide (1 mmol), phenylacetylene (1.5 mmol), Pd (OAc)2 (1 mol %), WEB (4 mL), EtOH (4 mL). b Isolated yields.
at the para position are much more reactive than aryl halides bearing electron donating groups. Thus, to investigate the effects of the new catalytic system with an electron-donating substrate, we performed the reaction between 4-iodotoluene and phenylacetylene under similar reaction conditions. It is surprising to see that 4iodotoluene gave superior product formation compared to 4iodonitrobenzene within shorter reaction time (Table 3, entry 5). The reaction also proceeds well in case of meta substituted iodotoluene (Table 3, entry 6). No significant differences were observed in the yield when phenyl acetylene was replaced by p-tolylphenylacetylene (Table 3, entry 7). However, the reaction of aryl halides with electron-donating groups, such as methoxy and amine gave the coupling products with slightly lower yields (Table 3, entries 8 and 9). Next, we examine the catalytic system for electronically diverse aryl acetylenes with aliphatic alkynes (Table 3, entries 10–16). In all cases, modest to good yield of desired cross-coupling products were observed. However, iodobenzene gave superior product formation with aliphatic alkynes (Table 3, entries 10, 13 & 15). Our next endeavor was to extend the scope of this greener protocol for coupling of aryl bromides with acetylene. We observed low conversion at room temperature for arylbromides. Hence, next we perform this reaction at 60 °C by taking the same catalyst loading. Aryl bromide having electron donating substituent viz. 4-CH3 rendered good yields of isolated cross-coupling products (Table 3, entries 18 and 19). However, the reaction of aryl bromide containing electron withdrawing substituents such as p-bromonitrobenzene with phenylacetylene did not proceed well and gave only 50% (Table 3, entry 20) conversion. Conclusions In conclusion, we have developed a convenient methodology for palladium catalyzed Sonogashira reaction under ligand and copper free conditions. The reaction is catalyzed by an in-situ generated catalytic system based on Pd(OAc)2 and WEB. The absence of additives, use of ethanol together with WEB as the solvent and the base
and wider substrate scope make it an attractive pathway for Sonogashira coupling reaction. This offers a greener alternative to the existing protocols since the reaction proceeds under ligand and copper free conditions in aqueous medium. Electronically diversified aryl iodides underwent the coupling reaction with electronically diversified aryl or aliphatic alkyne in excellent yields. The present method developed for the Sonogashira reaction offers many advantages including high conversion, high economy, the involvement of non-toxic green substrates, etc. Acknowledgments Authors are thankful to U.G.C, New Delhi for awarding Dr. D. S. Kothari Postdoctoral Fellowship to Dr. A. Dewan. M. S. thanks Tezpur University for providing institutional fellowship. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.07. 021. References and notes 1. (a) Sonogashira, K. In Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, I. E., Ed.; Wiley-VCH: Weinheim, Germany, 2002; Vol. 1, pp 493–529; (b) Marsden, A. J.; Haley, M. M. In Metal-Catalyzed Cross-Coupling Reactions; de Meijre, A., Diederich, F., Eds., 2nd ed.; Wiley-VCH: Weinheim, Germany, 2004; pp 317–394. 2. (a) Shao, F.; Weissleder, R.; Hilderbrand, S. A. Bioconjug. Chem. 2008, 19, 2487– 2491; (b) Shieh, P.; Bertozzi, C. R. Org. Biomol. Chem. 2014, 12, 9307–9320. 3. (a) Danilkina, N. A.; Vlasov, P. S.; Vodianik, S. M.; Kruchinin, A. A.; Vlasov, Y. G.; Balova, I. A. Beilstein J. Org. Chem. 2015, 11, 373–384; (b) Dai, C.; Cheng, Y.; Cui, J.; Wang, B. Molecules 2010, 15, 5768–5781. 4. (a) Wang, C. S.; Batsanov, A. S.; Bryce, M. R.; Martin, S.; Nichols, R. J.; Higgins, S. J.; Garcia-Suarez, V. M.; Lambert, C. J. J. Am. Chem. Soc. 2009, 131, 15647–15654; (b) Haiss, W.; Wang, C. S.; Grace, I.; Batsanov, A. S.; Schiffrin, D. J.; Higgins, S. J.; Bryce, M. R.; Lambert, C. J.; Nichols, R. J. Nat. Mater. 2006, 5, 995–1002; (c) Kaliginedi, V.; Moreno-Garcia, P.; Valkenier, H.; Hong, W. J.; Garcia-Suarez, V. M.; Buiter, P.; Otten, J. L. H.; Hummelen, J. C.; Lambert, C. J.; Wandlowski, T. J. Am. Chem. Soc. 2012, 134, 5262–5275; (d) Marques-Gonzalez, S.; Yufit, D. S.; Howard, J. A. K.; Martin, S.; Osorio, H. M.; Garcia-Suarez, V. M.; Nichols, R. J.; Higgins, S. J.; Cea, P.; Low, P. J. Dalton Trans. 2013, 42, 338–341; (e) MorenoGarcia, P.; Gulcur, M.; Manrique, D. Z.; Pope, T.; Hong, W.; Kaliginedi, V.; Huang, C.; Batsanov, A. S.; Bryce, M. R.; Lambert, C.; Wandlowski, T. J. Am. Chem. Soc. 2013, 135, 12228–12240; (f) Rigaut, S. Dalton Trans. 2013, 42, 15859– 15863. 5. Long, N. J.; Williams, C. K. Angew. Chem., Int. Ed. 2003, 42, 2586–2617. 6. (a) Huan, X.; Wang, D.; Dong, R.; Tu, C.; Zhu, B.; Yan, D.; Zhu, X. Macromolecules 2012, 45, 5941–5947; (b) Liu, H.; Zhang, Y.; Hu, J.; Li, C.; Liu, S. Macromol. Chem. Phys. 2009, 210, 2125–2137. 7. (a) Reed, M. W.; Moore, H. W. J. Org. Chem. 1988, 53, 4166–4171; (b) Harmrolfs, K.; Mancuso, L.; Drung, B.; Sasse, F.; Kirschning, A. Beilstein J. Org. Chem. 2014, 10, 535–543. 8. (a) Khong, S.; Kwon, O. J. Org. Chem. 2012, 77, 8257–8267; (b) Patil, N. T.; Raut, V. S. J. Org. Chem. 2010, 75, 6961–6964; (c) Sakai, N.; Tamura, K.; Shimamura, K.; Ikeda, R.; Konakahara, T. Org. Lett. 2012, 14, 836–839; (d) Liu, B.; Gao, H.; Yu, Y.; Wu, W.; Jiang, H. J. Org. Chem. 2013, 78, 10319–10328. 9. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467– 4470; (b) Eckhardt, M.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 13642–13643; (c) Mino, T.; Suzuki, S.; Hirai, K.; Sakamoto, M.; Fujita, T. Synlett 2011, 1277–1280. 10. (a) Urgaonkar, S.; Verkade, J. G. J. Org. Chem. 2004, 69, 5752–5755; (b) Lauterbach, T.; Livendahl, M.; Rosellon, A.; Espinet, P.; Echavarren, M. A. Org. Lett. 2010, 12, 3006–3009; (c) Fleckenstein, C. A.; Plenio, H. Green Chem. 2008, 10, 563–570; (d) Liang, Y.; Xie, Y.-X.; Li, J.-H. J. Org. Chem. 2006, 71, 379–381; (e) Yi, C.; Hua, R. J. Org. Chem. 2006, 71, 2535–2537; (f) Neumann, K. T.; Laursen, S. R.; Lindhardt, A. T.; Bang-Andersen, B.; Skrydstrup, T. Org. Lett. 2014, 16, 2216–2219. 11. (a) Mori, A.; Kawashima, J.; Shimada, T.; Suguro, M.; Hirabayashi, K.; Nishihara, Y. Org. Lett. 2000, 2, 2935–2937; (b) Yamamoto, Y. Chem. Rev. 2008, 108, 3199– 3222. 12. Finke, A. D.; Elleby, E. C.; Boyd, M. J.; Weissman, H.; Moore, J. S. J. Org. Chem. 2009, 74, 8897. 13. Negishi, E.-I.; Anastasia, L. Chem. Rev. 2003, 103, 1979–2017. 14. Gogoi, A.; Dewan, A.; Bora, U. RSC Adv. 2015, 5, 16–19. 15. (a) Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 927–928; (b) Bohm, V. P. W.; Herrmann, A. W. Eur. J. Org. Chem. 2000, 3679–3681; (c) Hundertmark, T.; Littke, A. F.; Buchwald, S. L.; Fu, G. C. Org. Lett. 2000, 2, 1729–1731; (d)
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22. Boruah, P. R.; Ali, A. A.; Saikia, B.; Sarma, D. Green Chem. 2015, 17, 1442–1445. 23. Boruah, P. R.; Ali, A. A.; Chetia, M.; Saikia, B.; Sarma, D. Chem. Commun. 2015, 11489–11492. 24. Saikia, B.; Borah, P.; Barua, N. C. Green Chem. 2015, 17, 4533–4536. 25. Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873–2920. 26. General experimental procedure for Sonogashira reaction: A mixture of aryl halide (1 mmol), terminal acetylene (1.5 mmol) and Pd(OAc)2 (1 mol %) in WEB/ethanol (1:1, 8 mL) was stirred for the indicated time at 60 °C. After completion of the reaction (vide TLC), the reaction solution was extracted with ethyl acetate (4 10 mL). The products were purified by column chromatography over silica gel using n-hexane/ethyl acetate (9: 1 v/v) to obtain the desired coupling products. The products were characterized by comparing 1H, 13C NMR spectroscopic data and GC–MS data with authentic samples.