Uncovering the mechanism leading to the synthesis of symmetric and asymmetric Tröger's bases

LANZA, PRISCILA AILÍN; DUSSO, DIEGO; RAMIREZ, CRISTINA LUJÁN; PARISE, ALEJANDRO RUBÉN; CHESTA, CARLOS ALBERTO; MOYANO, ELIZABETH LAURA; VERA, D. MARIANO A.

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

WILEY-V C H VERLAG GMBH

Año: 2019

1434-193X

Tröger´s bases have been attracting great interest due to their potential applications innanoelectronics, supramolecular chemistry, molecular recognition, biological activity andauxiliaries for asymmetric synthesis. However, a detailed step by step proposal for the mechanismleading to the production of these compounds is still uncovered. A set of five model syntheses ofsymmetric and asymmetric Tröger´s base derivatives starting from substituted anilines andformaldehyde was done and envisaged as representative for understanding the underlyingmechanism. All reasonable pathways were thoroughly scanned by means of DFT calculations. The highest energy TS was associated with the entrance of the first formaldehyde which produces thefirst out of three key carbocations. The last step, the closure of the methylene-bridged diazocyneheterocycle was also found of kinetic relevance and as a source of stable intermediates orbyproducts. The whole mechanistic picture would provide keys for the rational planning of thesynthesis of these compounds.