AuCl3-Catalyzed Propargylation of Arenes with N-Tosylpropargyl Amine: Synthesis of 1,3-Diarylpropynes

Abstract

1,3-Diarylpropynes are an important class of building blocks in organic synthesis. One of the most useful method for these compounds is a transition metal-catalyzed propargylation of electron-rich aromatics with propargyl alcohols. The use of (dppm)Re(O)Cl3/AgPF6, [Cp*RuCl(μ2-SMe)2RuCp*(OH2)]OTf, NaAuCl4·2H2O, AuCl3, BF3·OEt2, FeCl3, BiCl3, p-TsOH TiCl4/Et3N, and iodine has been reported. As the precursors of the corresponding propargyl cations, the use of propargyl alcohol is the most popular and the acetate of propargyl alcohol or O-propargyl trichloroacetimidate were also examined very recently. To the best of knowledge, synthesis of 1,3-diarylpropynes has not been examined starting from propargylic amine derivatives. Generation of carbocationic species by C-O bond cleavage have been studied and used extensively in the Friedel-Crafts chemistry. However, limited number of papers has been reported on the generation of carbocation by C-N bond cleavage, which involved the cases of DCC (1,3-dicyclohexylcarbodiimide), sulfonamide and some amide derivatives. In these respects, we reasoned that the reaction of N-tosyl derivative of propargyl amine and arenes could provide another useful method of 1,3-diarylpropynes (Scheme 1). Thus we prepared N-tosylpropargyl amine 1, as the representative example, by the reaction of N-tosylimine and phenylacetylene as reported and examined the feasibility for the synthesis of 1,3-diarylpropynes 3. Initially, we examined the reaction of 1 and 1,3-dimethoxybenzene (2b) under various conditions (Table 1). The use of AuCl3, FeCl3, InCl3, p-TsOH and montmorillonite K10 was examined and the results are summarized in Table 1. The use of InCl3, p-TsOH and montmorillonite K10 at room temperature was completely ineffective (entries 2, 5, and 7). When the reaction mixture was heated to reflux we could isolate desired product 3b in moderate yields (70-83%, entries 3, 6, and 8). The use of FeCl3 and AuCl3 were all efficient at room temperature (entries 1 and 4). Based on mildness, reaction time, the amount of used catalyst, and the yield of 3b, we thought AuCl3 is the best choice among the trials. With this optimized conditions we examined the reaction of 1 and various arene nucleophiles including anisole (2a), 1,2,3-trimethoxybenzene (2c), furan (2d), 2-methylfuran (2e), pyrrole (2f), phenol (2g), and 2-naphthol (2h). The corresponding 1,3-diarylpropynes 3a-h were isolated in good to excellent yields except for the case of pyrrole (entry 6). The reaction of 1 and pyrrole produced 3f in only 41% (10 mol% AuCl3, refluxing, 5 h). Besides of electron-rich arenes, allyltrimethylsilane can also be used in the reaction efficiently and we obtained compound 4 in 91% yield (Scheme 2). In summary, we disclosed an efficient AuCl3-catalyzed synthesis of 1,3-diarylpropynes from N-tosylpropargylamine with electron-rich arenes under mild conditions. Scheme 1 Table 1. Optimization of reaction conditions between the reaction of 1 and 2b