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.

Ruthenium(II)-Catalyzed Selective C–H Bond Activation of Biindoles and Coupling with Sulfoxonium: An Efficient Access to Pyrido[1,2-a:4,3-b′]diindole frameworks

“…Ila and co-workers reported the construction of pyrido[1,2- a :4,3- b ]diindole analogues through a Nenitzescu-type reaction of 1,2,3,4-tetrahydro-β-carboline-derived enaminones with 1,4- benzoquinone at room temperature for 48 hours. 8a The Vishwakarma group developed a two-step synthesis using ortho -halo-substituted glyoxal and tryptamine through a tandem dehydrative condensation followed by dehydrogenation to obtain the biindole alkaloid fascaplysin. 9 Other synthetic routes have also been reported for synthesizing the pyrido[1,2- a :4,3- b ′]diindole framework.…”

α-Iodo-α,β-Unsaturated Ketones as Vicinal Dielectrophiles: Their Reactions with Dinucleophiles Provide New Annulation Protocols for the Formation of Carbo- and Heterocyclic Ring Systems

“…Numerous methods are now available for achieving these, with more generalizable and thus more versatile variants being of particular interest. , The pursuit of such possibilities often involves identifying formally neutral synthetic equivalents for dianionic and/or dicationic species. In this connection, 1,2- or vicinal dielectrophiles have considerable potential, but compounds that can serve directly in this role are rather limited, with the majority of studies having been confined to those using oxalyl chloride (and certain derivatives), 1,2-dihaloethanes, and α-halogenated acid chlorides for this purpose. , Such species are often labile ones and such that on reaction with strong nucleophiles, polymerization, elimination, formation of open-chain products, SET, and decomposition processes are frequently observed. Accordingly, the identification of more suitably reactive vicinal dielectrophiles that ameliorate or even avoid such problems could provide useful new means for achieving annulation reactions.…”