Effiziente und vielseitige Indol‐Synthese aus Enaminen und Iminen mithilfe dehydrierender Kreuzkupplung

Ruthenium‐Catalyzed Synthesis of Indoles from Anilines and Epoxides

“…[d] Yield of the mixture of regioisomers, in these cases, with 3-butyl indoles as the major products. and high-vacuum drying, the corresponding indoles (5)(6)(7)(8)(9)(10)(11)(12)(13) in the reported yields.…”

“…[6] More recently, Glorius and co-workers have developed a palladium-catalyzed oxidative cyclization of N-aryl enamines derived from anilines and ketones to afford the corresponding indoles (Scheme 1 d). [7] Alternatively, the research groups of Yoshikai, [8] Jiao, [9] Cacchi, [10] Zhao, [11] and Liang [12] have explored the use of different metals, oxidants, and reaction conditions to improve the substrate scope. From our point of view, the ideal synthesis of indoles would be one that involves the direct connection of anilines with C2 fragments, such as alkenes or alkynes (Scheme 1 e).…”

“…Finally, the reactivity of different epoxides, including aromatic and aliphatic derivatives, was studied. The reaction of four selected anilines (1 a, b, m and n) with 4-(chlorophenyl)oxirane (6) provided the corresponding indoles 10 a, b, m and n with the para-chlorophenyl group in the 2-position as the major products (71-86 %, Table 4, entries [5][6][7][8]. It is important to note that the same reaction, under the conditions described in the Table 2 with p-TsOH as the only additive, resulted in very low yields.…”

“…Encouraged by these results, we were intrigued about the reactivity of an aliphatic epoxide. To our delight, the zinc-catalyzed ring opening of 1,2-epoxyhexene (7) with aniline and para-toluidine at room temperature, followed by rutheniumcatalyzed cyclization in the presence of p-TsOH as an additive, took place efficiently to give the corresponding 2-butyl indoles 11 a and b in good yields (71-74 %, Table 4, entries 9 and 10). However, the same reaction with 1-naphthylamine provided the desired indole 11 m in an excellent yield, but as a mixture of isomers (84 %, 45:55, Table 4, entry 11), probably due to the higher steric hindrance caused by the naphthyl group during the ring opening of the epoxide.…”

“…We observed no reaction in the absence of p-TsOH. Carboxylic acids such as para-toluic acid or other Lewis acids [Zn(OTf) 2 , SnCl 2 ·2H 2 O, Al(OTf) 3 ] resulted in low to moderate yields, whereas the use of only 5 mol % of para-toluenesulfonic acid resulted in a higher yield (79 %,Table 1, entries[6][7][8][9][10][11]. Reactions in DMF and DMSO did not provide the corresponding indole in good yields, but this domino sequence can be performed effectively in toluene and 1,4-dioxane, and in the last case 3 a was obtained in 99 % yield(Table 1,entries 12-15).…”