Formal [3 + 2] Cycloadditions via Indole Activation: A Route to Pyrroloindolines and Furoindolines

Abstract

Here, we describe a novel [3 + 2] cycloaddition of 3-substituted indoles with vinyl aziridines and vinyl epoxides that provides a straightforward approach to pyrroloindolines and furoindolines bearing vinyl groups (up to 96% yield and 9:1 dr). In contrary to previous reports involving Lewis acid activation, this work reports successful reactions based on the activation of indole using t-BuOK and BEt (triethylborane), thereby preserving the free N-H group on indoles. In addition, a gram-scale reaction and a ring-closing metatheis reaction are performed to provide good demonstrations of the synthetic utility of this approach.

Pd-Catalyzed Asymmetric Dearomative Cycloaddition for Construction of Optically Active Pyrroloindoline and Cyclopentaindoline Derivatives: Access to 3a-Aminopyrroloindolines

“…Some related studies have also documented the stereoselective construction of structurally diverse polycyclic indoles . In addition, vinyl aziridines, offering a unique combination of reactivity, synthetic flexibility, and atom economy, are multifaceted building blocks for the construction of a number of nitrogen heterocyclics, but few successful examples are known for formation of pyrroloindoline derivatives . In 2017, Hyland et al reported Pd(0)/BPhen complex-catalyzed [3 + 2] cycloaddition for diastereoselective synthesis of racemic 3a-nitropyrroloindolines and cyclopenta­[ b ]­indolines in high yields .…”

Domino Ring-Opening Cyclization of Activated Aziridines with Indoles: Synthesis of Chiral Hexahydropyrroloindoles

“…Many interesting synthetic routes have been developed for this purpose, e.g., [3 + 2] cycloaddition, electrophilic addition/cyclization, cyclopropanation/ring opening/iminium cyclization (CRI reaction), Fischer indolization, copper catalyzed cyclization of iodo-tryptophans and organocatalytic cascade addition-cyclization, etc . Aziridines , have also been exploited for the synthesis of pyrroloindolines .…”

Recent Advances in Synthetic Strategies for the C4a,C9a-Fused Tetracyclic Hydrocarbazole Core Structure of Minfiensine and Related Akuammiline Alkaloids

“…[32][33][34] In 2015, Zhao and co-workers developed a formal [3+2] cycloaddition of indole with aziridines to construct tetracyclic hydrocarbazole (Scheme 7). 35 The formal 36 In this reaction, indole 45 was activated with triethylborane and potassium tert-butoxide, and the resulting borate 46 underwent nucleophilic addition at C3 with allylaziridine 47, followed by cyclization to furnish tetracyclic hydrocarbazole 48 in 38% yield with 2:1 dr.…”