Palladium-Catalyzed Tandem Nucleophilic Addition/C–H Functionalization of Anilines and Bromoalkynes for the Synthesis of 2-Phenylindoles

Abstract

A novel and efficient palladium-catalyzed annulation of anilines with bromoalkynes for the synthesis of 2-phenylindoles has been described. This approach features excellent regio-and stereoselectivities and good functional group tolerance. Preliminary mechanistic studies indicate that anilines undergo anti-nucleophilic addition to bromoalkynes to generate (Z)-N-(2-bromo-1-phenylvinyl) anilines, followed by sequential C−H functionalization to deliver different substituted 2-phenylindoles. This method provides potential applications for the construction of various biologically active compounds.

Palladium‐Catalyzed Tandem Cyclization of Bromoalkynes, Anilines and CO: Access to 1,3‐Substituted Maleimides

“…Based on these experimental results and relevant literatures, [6,7,11,12b] two possible mechanisms for this tandem cyclization are proposed in Scheme 3. In path A, the nucleophilic addition reaction of 1 a with bromoalkyne and carbon monoxide generates the intermediate Int‐1 , which would be converted into the vinylpalladium complex Int‐2 through oxidative addition.…”

“…[5] Among them, our group recently has developed a palladiumcatalyzed nucleophilic addition/annulation of bromoalkynes with benzoic acids for the synthesis of isocoumarins. [6] Recently, we have reported the synthesis of 2-phenylindoles from bromoalkynes and anilines via nucleophilic addition/CÀ H functionalization strategy [7] (Scheme 1a). However, the existing research has primarily focused on the two-component annulations of haloakynes, the multi-component tandem cyclizations of haloalkynes are seldom reported, and it is challenging to control the sequence of reactions in multi-component reactions.…”

Metal‐Catalysed Synthesis of Benzofused Five‐Membered N/O/S‐Heterocycles, a Progressive Area in Synthetic Organic Chemistry

“…In 2023, the same group published a successful approach for the construction of 2‐phenylindoles 16 via palladium‐catalysed annulation of anilines 14 with bromoalkynes 15 (Scheme 5). [29] Excellent regio‐ and stereo‐selectivity as well as good functional group tolerance were observed in the reaction. Substitutions of aniline and alkyne showed profound electronic effects on the product yield.…”

Cascade Electrochemical Aerobic Oxygenation of 2-Substituted Indoles and Electrochemical [5 + 3] Annulation with Amidines: Access to Eight-Membered Benzo[1,3,5]triazocin-6(5H)-ones

“…White solid . c 1 H NMR (400 MHz, CDCl 3 ) δ 8.07 (s, 1H), 7.49–7.45 (m, 1H), 7.45–7.43 (m, 1H), 7.33–7.26 (m, 4H), 7.05–7.02 (m, 1H), 6.54 (dd, J = 2.0, 0.8 Hz, 1H), 2.50 (s, 3H), 2.47 (s, 3H).…”

“…2-Phenyl-1 H -indole ( 1a ), 2-methyl-1 H -indole ( 1j ), and 1 H -indole ( 1l ) are commercially available. 2-Aryl-1 H -indoles ( 1b – 1i , 1k , 1m – 1o, 1q – 1s ) were synthesized from acetophenone and phenylhydrazine hydrochlorides via Fisher indole synthesis . 5-Nitro-2-phenyl-1 H -indole ( 1p ) was prepared according to the literature procedures.…”