Tunable Electrocatalytic Annulations of o-Arylalkynylanilines: Green and Switchable Syntheses of Skeletally Diverse Indoles

Abstract

Tunable electrocatalytic annulation reactions of oarylalkynylanilines have been established, leading to green and divergent syntheses of skeletally diverse indoles by adjusting the electrolytes and the solvents. The presence of ammonium halides as the electrolytes enabled the halogenation of o-arylalkynylanilines to give C3-halogenated indoles whereas naphtho[1′,2′:4,5]furo[3,2b]indoles could be obtained by changing the electrolyte from ammonium halides to KI. Interestingly, by combining acetone as the solvent and both NH 4 I and NH 4 Cl as the electrolytes, the reaction worked through an intramolecular annulation and [5 + 1] cyclization cascade to form naphtho[1′,2′:5,6][1,3]oxazino[3,4a]indoles.

Halogenative Annulation Reactions of Alkyne-Tethered N- and O-Containing Arenes: Methods for Accessing Aryl-Fused Halogenated N- and O-Heterocycles

“…In recent years, several additional methods were reported for the synthesis of 3-haloindoles. One notable method was reported by Jiang in 2021 9 using electrochemistry as a green approach to prepare various indole derivatives from 2-alkynylanilines. The electrochemical aspects of this transformation were particularly interesting as the outcomes of the reaction depended on the electrolytes and solvents.…”

2‐(Alkynyl)anilines and Derivatives — Versatile Reagents for Heterocyclic Synthesis

“…An interesting divergent transformation of 2‐hydroxy‐2’‐amino‐diphenylacetylenes 156 could also be achieved by the means of electrochemistry (Scheme 49). [148] Control is provided by both the solvent and inorganic salts additives. The formation of five‐membered ring in 157 takes place in the presence of KI and ethanol as a solvent, while the formation of a six membered ring occurs in acetone.…”

A regiodivergent Truce–Smiles rearrangement: a strategy for the synthesis of arylated indoles promoted by KN(SiMe3)2

“…On the other hand, cyclization of a metallated ortho-amino group on the alkyne forms an indolylmetal intermediate that can be trapped by external electrophiles, for example, via the Heck reaction, 60 Sonogashira reaction, 61 or Suzuki reaction, 62,63 among others (Scheme 1b). [64][65][66][67][68][69][70][71][72][73][74] In the current study (Scheme 1c), we employ 2-arylpropargyl anilines with weakly acidic benzylic sp 3 C-H bonds. Thus, base initiated deprotonation-nucleophilic attack of the sulfo-namido nitrogen on the alkynyl moiety results in cyclization and produces a reactive sp 2 -hybridized carbanion.…”