PMA-SiO2 catalyzed synthesis of β-keto enol ethers

Available online at www.sciencedirect.com Chinese Chemical Letters 19 (2008) 767–770 www.elsevier.com/locate/cclet PMA-SiO2 catalyzed synthesis of b-keto enol ethers P. Srihari *, S.S. Mandal, J.S.S. Reddy, R. Srinivasa Rao, J.S. Yadav Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500007, India Received 18 December 2007 Abstract An efficient conversion of b-diketones into corresponding b-keto enol ethers with catalytic amount of PMA-SiO2 has been achieved. # 2008 P. Srihari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: b-Keto enol ethers; b-Diketones Keto enol ethers are found to be present in several key intermediate compounds [1] including complex organic molecules and have gained significant importance for their preparations [2]. Not only being the core structure of several natural and synthetic biologically active products, they also serve as a source of dienophiles in Diels Alder reactions [3] and are sometimes used as precursors for many terpenoids synthesis [4]. There are several precedences for the preparation of b-keto enol ethers from cyclic b-diketones which includes reaction of alcohols with b-diketones in presence of either p-toluenesulfonic acid monohydrate [5] under reflux temperature or InCl3 supported on silica or TiCl4 [6] or B(C6F5)3 [7] or iodine [8] or P2O5-SiO2 [9] or ceric ammonium nitrate [10] or diazomethane [11]. Apart from these, metal triflate such as ytterbium triflate [12] has also been used. Synthesis of cyclic b-keto enol ethers can also be achieved by treating 3-chlorocycloalk-2-enones with methoxide [13]. However, many of these reactions suffer either due to difficulty in handling the reagents or require harsh conditions or tedious work up procedures and thus a simple and reliable procedure is always desired. In the present communication, we wish to report an efficient synthesis of b-keto enol ethers using silica supported phosphomolybdic acid [14] as a reusable and green catalyst (see Scheme 1). Recently, we have shown that PMA-SiO2 can be utilized as an efficient solid reagent system that catalyzes various reactions such as deacetalization of acetals [15], synthesis of 2,3-glycopyranosides by Ferrier rearrangement [16] and heteroatom centered nucleophilic substitution reactions of aryl propargyl alcohols [17]. In continuation to explore further scope of this reagent system, we investigated whether b-keto enol ethers would be synthesized starting from cyclic b-diketone and alcohol utilizing PMA-SiO2 as a catalyst. Towards these studies, we first examined simple unsubstituted 1,3-cyclohexanedione with methyl alcohol in presence of PMA-SiO2. Within 1 h, complete consumption of starting material along with simultaneous formation of a new product was observed. The obtained product was isolated and characterized as 3-methoxy-2-cyclohexene-1-one by regular spectroscopic analysis. * Corresponding author. E-mail address: [email protected] (P. Srihari). 1001-8417/$ – see front matter # 2008 P. Srihari. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2008.05.006 768 P. Srihari et al. / Chinese Chemical Letters 19 (2008) 767–770 Scheme 1. Encouraged with this result and to further study the generality and scope of the reaction, various alcohols including allylic, propargylic and benzylic alcohols were treated with b-diketones (see Table 1) in presence of PMA-SiO2. All alcohols responded well under this protocol to yield the corresponding b-keto enol ethers. Propargylic alcohol took longer reaction time and heating was necessary for completion of reaction when compared to other alcohols. Even the secondary alcohols such as isopropyl alcohol and cyclopentenyl alcohols responded well with longer duration and moderate yields. The reaction did not proceed well when the reaction was run without PMA in silica gel. With PMA alone only 10% conversion of the starting material to the corresponding product was observed after 5–6 h. Thus, it was necessary to use Table 1 PMA-SiO2 catalyzed synthesis of cyclic enol ethers Time (h) Yieldb (%) References for products 1 1.0 92 [7,8,10] 2 1.5 90 [7] 3 2.0 9 [8,10] 4 3.0 84 c [7,9] 5 2.0 96 – 6 2.5 91 – 7 1.5 92 [8] 1.0 98 [8,10] 2.0 93 [9] Entry 8 9 1,3-Diketone Alcohol MeOH 2g Producta 769 P. Srihari et al. / Chinese Chemical Letters 19 (2008) 767–770 Table 1 (Continued ) Time (h) Yieldb (%) References for products 10 1.5 96 – 11 3.0 87 – 12 1.0 90 – 13 2.5 92 – 14 4.5 62 [8,9] 15 6.0 65 [9] 16 7.0 60 [10] Entry a b c 1,3-Diketone Alcohol Producta All products were characterized by 1H NMR, IR and mass spectroscopy. Isolated yields after column chromatography. The reaction was carried out at 60 8C for 3 h. combination of PMA-SiO2 for reaction to progress with optimum yields. Also, to increase the yield and reduce the reaction time, attempts were made by increasing the amount of PMA-SiO2 from 0.01 to 0.1 eq., which ended with subtle change in the amount of yield obtained. The silica supported PMA catalyst was also characterized by FT-IR to confirm the existence of Keggin structure of PMA on silica. The IR spectrum suggested the retention of Keggin structure of PMA on silica. The used catalyst also showed the presence of bands related to Keggin ion after repeated use. This observation made us to investigate the reusability of the catalyst for the present reaction. Thus, the reaction of 1,3-cyclohexanedione with benzyl alcohol in presence of PMA-SiO2 was studied for recyclization. After the commencement of the reaction, the catalyst was filtered, dried and reused twice for the same process with the same substrate to result in consistent yields of the product compared with the first reaction (92%, 85% and 79%). The acid strength of the catalyst was measured by using potentiometric titration method [18] and found that the present catalyst shows very strong acid sites as it shows E value in the range of 600–650 mV. In conclusion, we have shown that PMA-SiO2 works as an efficient catalyst for the preparation of b-keto enol ethers from cyclic b-diketones and demonstrated an alternative and simple procedure for the synthesis of b-keto enol ethers from 1,3-diketones. Easy workup conditions with shorter reaction times and utilization of low concentration of the catalyst makes this protocol a very attractive procedure. Further investigations into the scope of PMA-SiO2 mediated reactions with enol ethers are in progress. 1. Experimental General procedure for the synthesis of b-keto enol ethers: 770 P. Srihari et al. / Chinese Chemical Letters 19 (2008) 767–770 To a solution of 1,3-diketone (1 mmol) and alcohol (1 mmol) in acetonitrile (4 mL) was added PMA-SiO2 (0.005 mmol) and the reaction mixture was stirred at room temperature for appropriate time. After complete consumption of the starting material as indicated by TLC, the reaction mixture was filtered and the filtrate was concentrated under vacuum to obtain crude product. The crude product was purified by column chromatography (ethyl acetate/hexane as eluent) to obtain pure b-keto enol ether. 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