The Development of a Palladium-Catalyzed Tandem Addition/Cyclization for the Construction of Indole Skeletons

Abstract

A palladium-catalyzed tandem addition/cyclization of 2-(2-aminoaryl)acetonitriles with arylboronic acids has been developed for the first time, achieving a new strategy for direct construction of indole skeletons. This system shows good functional group tolerance and remarkable chemoselectivity. In particular, the halogen (e.g., bromo and iodo) substituents are amenable to further synthetic elaborations thereby broadening the diversity of the products. Preliminary mechanistic experiments indicate that this transformation involves sequential nucleophilic addition followed by an intramolecular cyclization.

Palladium-Catalyzed Cascade Reactions of δ-Ketonitriles with Arylboronic Acids: Synthesis of Pyridines

“…The Liao group described Pd-catalyzed addition of arylboronic acids to carbonic ester substituted nitriles to synthesize spirooxindolyl oxazol-2­(5 H )-ones . Our group developed a one-step syntheses of 2-arylbenzo­[ b ]­furans and 2-aryl-1 H -indoles via sequential addition and intramolecular annulation reactions with hydroxy- or amino-substituted 2-phenylacetonitriles. , …”

Synthesis of N-Heterocycles via Transition-Metal-Catalyzed Tandem Addition/Cyclization of a Nitrile

“…Chen et al have also reported a Pd-catalyzed addition/cyclization reaction cascade to construct the indole scaffold (Scheme 26), 38 albeit being different from the above work. In this reaction, they have introduced a nucleophile, the aniline moiety, to accomplish the cyclization.…”

Regioselective Synthesis of 2‐Arylindoles via Palladium‐Catalyzed Cyclization of Phenylglyoxal and 2‐Anilinoacetophenones with Anilines

“…2‐(Phenyl)‐5‐phenyl‐1H‐indole (28c): Colorless solid; 43.4 mg; yield 87 %. 1 H NMR (300 MHz, CDCl 3 ) δ 8.29 (br, 1H, N‐H), 7.77 (s, 1H), 7.60 (ddt, J = 8.3, 4.8, 1.8 Hz, 3H), 7.45–7.34 (m, 6H), 7.31–7.13 (m, 3H), 6.81 (s, 1H).…”