Aza-Annulation of 1,2,3,4-Tetrahydro-β-carboline Derived Enaminones and Nitroenamines: Synthesis of Functionalized Indolizino[8,7- b]indoles, Pyrido[1,2-a:3,4-b′]diindoles, Indolo[2,3-a]quinolizidine-4-ones and Other Tetrahydro-β-carboline Fused Heterocycles

Abstract

Aza-annulation of novel 1,2,3,4-tetrahydro-β-carboline derived enaminones and nitroenamines with various 1,2- and 1,3-bis electrophiles, such as oxalyl chloride, maleic anhydride, 1,4-benzoquinone, 3-bromopropionyl chloride, itaconic anhydride, and imines (from formaldehyde and primary amines), has been investigated. These methodologies provide simple one-step pathways for efficient construction of highly functionalized tetrahydro-β-carboline 1,2-fused, five- and six-membered heterocyclic frameworks, such as indolizino[8,7-b]indoles, pyrido[1,2-a:3,4-b′]diindoles, indolo[2,3-a]quinolizidines, and pyrimido[1′,6′:1,2]pyrido[3,4-b]indoles, which are core structures of many naturally occurring indole alkaloids with diverse bioactivity.