Synthesis and structure of novel ferrocene-containing β-carbolines including polycondensed derivatives with the elements of planar-, central- and conformational chirality

•Synthesis and structure of functionalized ferrocene-containing β-carbolines.•Construction of novel alkaloid-like ferroceno-fused chiral heterocyclic scaffolds.•Tandem cyclization of tryptophan-based iminomethylferrocene carboxylic acids.•Imidazole-induced fragmentation of the ferrocene unit leading to fused fulvene.•DFT modeling of the elementary steps of the diastereoselective tandem cyclization.

Employing tryptamine or tryptophane methylester hydrochloride and (Sp)-2-formylferrocene-1-carboxylate as precursors by means of Pictet–Spengler reactions and subsequent intramolecular acylation effected by cyanuricfluoride or carbonyldiimidazole (CDI), the first representatives of ferrocene-containing β-carboline derivatives including polycyclic ferroceno/fused lactames, were prepared. In the course of CDI-mediated tandem cyclization of a tryptophane-derived carboxyferrocenyl-substituted β-carboline, a ring enlargement simultaneously taking place with the loss of the η5-C5H5Fe+ fragment of the fused ferrocene moiety, effected by the coordinating imidazole released from the reagent, led to a 4H-cyclopenta[7,8]azonino[5,4-b]indole as a minor product. The constitution and relative configuration of the new compounds with the elements of planar-, central- and conformational chirality were established by NMR methods including HMQC, HMBC and NOESY measurements supported by DFT modeling studies.

Graphical abstractA series of novel alkaloid-like alkaloid-like ferroceno-fused chiral heterocyclic scaffolds were prepared using a traditional sequence involving Pictet–Spengler reaction and a novel protocol based on tandem cyclization of tryptophan-based imines derived from (Sp)-2-formylferrocene carboxylic acid. The relative configuration of the products was established by NMR methods.Figure optionsDownload full-size imageDownload as PowerPoint slide