TMEDA‐Catalyzed Regioselective Decarboalkoxy C−N Bond Formation: A Unified Direct Access to Indolo[2,1‐a]isoquinoline and Dibenzopyrrocoline Alkaloids

Chemistry – An Asian Journal
2022.0

Abstract

An unprecedented TMEDA-catalyzed, regioselective, decarboethoxy direct C−N coupling protocol towards the synthesis of dibenzopyrrocolines 17 a–i and 5,6-dihydroindolo[2,1-a]isoquinoline 15 a–f/18 a–c alkaloids via the identification of N,N,N′,N′-tetramethylethylenediamine (TMEDA) as a homogeneous catalyst is reported. The transition-metal-free, TMEDA-catalytic novel protocol is operationally simple and showed a wide range of functional group tolerance and substrate compatibility. The gram-scale application and synthesis of naturally occurring Cryptaustoline (dibenzopyrrocoline) alkaloid, further highlights the importance and versatile nature of the developed protocol. This finding also offers a TMEDA-catalyzed direct synthesis of dibenzopyrrocolines and substituted 5,6-dihydroindolo[2,1-a]isoquinoline compounds in a one-pot. The probable reaction pathway involves the free-radical sequential approach via a single electron transfer (SET) mechanism. © 2022 Wiley-VCH GmbH.

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