Redox Isomerization via Azomethine Ylide Intermediates: N-Alkyl Indoles from Indolines and Aldehydes

Abstract

Indolines react with aromatic and heteroaromatic aldehydes to yield N-alkyl indoles in a benzoic acid catalyzed redox isomerization reaction. Azomethine ylides are intermediates in this process which was established by intramolecular [3 + 2] trapping experiments.

tert-Amino effect: the Meth-Cohn and Reinhoudt reactions (Review)

“…in the presence of acids led to dehydrogenation of the heterocycle and hydrogenation of the formed Schiff base resulting in the 1-substituted pyrrole 154 [108]. The reaction with indoline 155 similarly led to the indoles 156 [109,110]. Tunge and colleagues [108] suggested that a 1,3-migration of hydrogen was the key step of this process.…”

Organocatalytic C–H activation reactions

“…Later, Pan and Seidel independently extended this methodology to indolines using benzoic acid as the catalyst, conducting the reaction under reflux and microwave irradiation conditions, respectively, to generate indole 9 (Scheme 7) [18–19]. …”

“…However, Seidel pointed out that a 1,3-hydride shift will occur antarafacially and is geometry-forbidden. An alternative explanation is the formation of azomethine ylide intermediate 11 (Scheme 8) [19–20]. …”

“…In fact, Seidel and co-workers provided the experimental evidence for the existence of azomethine ylide intermediates in the Tunge pyrrole formation and in the formation of N -alkylindoles from indoline [19]. These reactions are considered C–H activation reactions, as during the azomethine ylide formation, the C–H bond that is cleaved is not activated by electron-withdrawing (such as ester) groups.…”

Synthesis of N-alkyl pyrroles via decarboxylation/dehydration in neutral ionic liquid under catalyst-free conditions

“…6 Subsequently, Pan's and Seidel's groups independently reported the synthesis of N-substituted indole via reaction between indoline and aldehyde in the presence of acid. [7][8] The reaction proceeded via intramolecular hydride transfer to the azomethine 25 ylide that was generated as intermediate during the reaction to afford product. In further advancement of the methodology Kumar and Rao reported synthesis of N-alkyl pyrroles by reaction between 4-hydroxy proline and aldehyde in DMSO which was required to be added slowly for efficient reaction.…”