Ruthenium‐Catalyzed Selective C−C Coupling of Allylic Alcohols with Free Indoles: Influence of the Metal Catalyst

Abstract

Versatile reactive activities of allyl alcohols with free indoles in C-H functionalization reactions were investigated. Direct alkylation or cascade cyclization reactions could be selectively controlled based on the catalyst system: Ru(PPh ) Cl provided C3-substituted β-ketone indoles whereas [Ru(p-cymene)Cl ] yielded cyclized indoles.

Ruthenium-Catalyzed C–H Activations for the Synthesis of Indole Derivatives

“…Besides indoles, a broad scope of substances, such as pyrroles and other azoles, are exhibited with further applications leading to 3,4-fused tricyclic indoles. Dong [57] also reported direct alkylation or cascade cyclization reactions on C3 of indoles (Scheme 32). With the Ru(PPh3)3Cl2 catalyst, the reaction provides C3-substituted β-ketone indoles and [Ru(p-cymene)Cl2]2 affords 5,12-dihydrobenzo [6,7] cyclohepta [1,2-b] indoles.…”

Synthesis of Indolo[2,1-a]benzazepinones through Rhodium-Catalyzed Cascade Reactions of 2-Arylindoles with Allyl Alcohols

“…Deuterium was observed at both ortho -positions of phenyl ring (68%) and C3 position of indole ring (74%) when the reaction was carried out in the absence of 2 using DCE/CD 3 OD as the solvent (Scheme c). The H/D exchange of ortho -positions of the phenyl ring indicated that the reaction underwent coordination of nitrogen, and the H/D exchange of the indole ring may be due to the strong nucleophilic property of C3-position which easily attacks rhodium cation followed by metal protonation . Another control experiment showed that no deuterium exchange at the ortho -positions of the phenyl ring was seen in the absence of a rhodium catalyst (Scheme d), suggesting that the rhodium catalyst is essential for this reaction.…”

“…In 2017, Dong et al reported a Ru-catalyzed cascade C–H allylation and oxidative annulation of 2-phenylindoles with allyl carbonates (Scheme a) . Subsequently, they studied Ru-catalyzed cascade cyclization reactions of 2-phenylindoles with allyl alcohols (Scheme b) . Inspired by these pioneering studies and to broaden the scope of nitrogen heterocycles readily accessible via C–H activation/annulation of 2-arylindoles, we envisioned the use of 2-arylindoles as building blocks for the synthesis of indolo­[2,1- a ]­benzazepinones via a cascade reaction involving C–H activation/intramolecular annulation in the presence of various allyl alcohols (Scheme c).…”

“… Due to the less electrophilic and higher steric hindrance of ketones than aldehydes, the subsequent nucleophilic addition/cyclization process was potentially affected. Although the expected cyclized product was not obtained, the reaction was interesting since almost all the C–H functionalizations involving 2-arylindoles reported to date afforded cyclization products. − Thus, other α-substituted allyl alcohols such as 2f and 2g were further investigated. As excepted, 2f also reacted with 1a smoothly to afford the corresponding alkylated and alkenylated products 3af and 3af′ in reasonable yields.…”

“…On the basis of the above observations and previous reports, − a possible catalytic cycle is proposed (Scheme S2). First, an active catalyst Cp*Rh­(OAc) 2 is generated via halide abstraction.…”