A Straightforward Synthesis of 5‐Methylaaptamine from Eugenol, Employing a 6π‐Electrocyclization Reaction of a 1‐Azatriene

摘要: Aaptamine, isolated from tropical marine sponges of the Demospongiae class, is most prominent member a growing family natural products. Many aaptaminoids have been shown to interesting biological activity. The efficient access 5-methylaaptamine, an unnatural analogue aaptamine, was achieved by using economic and naturally-occurring eugenol as starting material. synthesis involved preparation 5-aminoeugenol derivative through successive nitration, O-methylation, nitro group reduction reactions. An Elderfield–Johnson sequence employed synthesize N-tosyl-5-allyl-7,8-dimethoxydihydro-1H-quinolin-4-one ring system. A catalytic double-bond isomerization followed carbonyl methoximation 6-π electrocyclization 1-azatriene motif afforded 2,3-dihydro-1H-benzo[de][1,6]naphthyridine tricyclic intermediate, which underwent reductive desulfonylation dehydrogenation afford target product.