Regio-Selective C3- and N-Alkylation of Indolines in Water under Air Using Alcohols

Abstract

We disclosed a regio-selective C–H and N–H bond functionalization of indolines using alcohols in water via tandem dehydrogenation of N-heterocycles and alcohols. A diverse range of N- and C3-alkylated indolines/indoles were accessed utilizing a new cooperative iridium catalyst. The practical applicability of this methodology was demonstrated by the preparative-scale synthesis and synthesis of a psychoactive drug, N,N-dimethyltryptamine. A catalytic cycle is proposed based on several kinetic experiments, series of control experiments and density functional theory calculations.

Tandem synthesis of N-methylated tertiary amines via three-component coupling of carbonyl compounds, amines, and methanol

“…The formation of a pyridonate species (I-1) was confirmed by NMR, IR, and ESI-MS analysis. 41 Next, when the reaction was performed at 100 1C for 1 h, the formation of an Ir-H species (I-2) was determined by 1 Based on the control experiments and the previous literature reports, 42,43 a possible catalytic cycle is proposed for the tandem transformation (Scheme 4). The reaction proceeds via two cycles, transfer hydrogenation of the imine to form secondary amine (Cycle-I), followed by borrowing hydrogenation to form N-methylated tertiary amine (Cycle-II).…”

“…The formation of a pyridonate species ( I-1) was confirmed by NMR, IR, and ESI-MS analysis. 41 Next, when the reaction was performed at 100 °C for 1 h, the formation of an Ir–H species ( I-2 ) was determined by 1 H NMR [Scheme 3(II)]. The involvement of this active Ir–H species was also corroborated by carrying out the optimized reaction with separately synthesized Ir–H complex, which delivered 94% of the desired product [Scheme 3(III)].…”

Nickel-Catalyzed Direct Synthesis of N-Substituted Indoles from Amino Alcohols and Alcohols

“…13 Lately, Kundu and co-workers reported the regioselective C3-and N-alkylation of indolines using alcohols in water. 14 abundance and low cost of first-row transition metals as compared to noble metals, their use in catalytic reactions is highly advantageous. 15 The research group of Rueping reported the first manganese-pincer-complex-catalyzed selective synthesis of C-and N-alkylated indoles directly from indolines and primary alcohols.…”

“…Hence, the development of alternative strategies to obtain N -alkylated indoles is of continuing interest. Recently, the N–H bond functionalization of indolines using alcohols was studied for the synthesis of N -alkylated indoles. , In 2017, the iridium-catalyzed regioselective C- versus N -alkylation of indolines using primary alcohols was reported by Wang and co-workers . Lately, Kundu and co-workers reported the regioselective C3- and N -alkylation of indolines using alcohols in water .…”

“…Recently, the N–H bond functionalization of indolines using alcohols was studied for the synthesis of N -alkylated indoles. , In 2017, the iridium-catalyzed regioselective C- versus N -alkylation of indolines using primary alcohols was reported by Wang and co-workers . Lately, Kundu and co-workers reported the regioselective C3- and N -alkylation of indolines using alcohols in water . In view of the relatively high abundance and low cost of first-row transition metals as compared to noble metals, their use in catalytic reactions is highly advantageous .…”