Access to the Pyrroloindoline Core via [3 + 2] Annulation as well as the Application in the Synthetic Approach to (±)-Minfiensine

Abstract

A [3 + 2] formal cycloaddition reaction using aza-oxyallyl cation as a synthetic synthon was developed to construct the pyrroloindololine core. With this novel method, a variety of C3-substituted indoles were readily converted into the corresponding pyrroloindoline analogues at room temperature in the mixed solvents. To further demonstrate the utility of this method, a synthetic approach to the total synthesis of (±)-minfiensine was developed in quite concise fashion.

Transition‐Metal‐Free Synthesis of N‐Hydroxy Oxindoles by an Aza‐Nazarov‐Type Reaction Involving Azaoxyallyl Cations

“…[16] In 1993,t he groupo f Kikugawas howede videncef or azaoxyallylc ationi ntermediates, [17] butthere hadnot been much progress untilJeffrey and co-workers reported thef irst practical[ 4 + +3] cycloaddition involvingazaoxyallyl cations. [22] Consideringthatthisintermediatecould be trappedby Scheme 1. Our grouph as also explored thea pplication of azaoxyallylcations as synthons in synthetica pproachest owards (AE)-minfiensine.…”

“…[*] W. Ji when a-bromo-N-hydroxy anilide( 7,R= OH)w as subjected to thes ystem, [20][21][22] thed esired oxindole 8 (R = OH)w as obtained in 90 %yield (entry 5).Thus, 7 (R = OH)was chosen as themodel substratefor theinitial survey.Replacing KHCO 3 with either K 2 CO 3 or Et 3 Na sthe base resulted in loweryield (entries 6a nd 7).T he solventw as so crucialt hatt he reaction conductedincommonsolventsgavethe eliminationproduct 9 as them ainproduct withoutforming 8 (entries 8-11).…”

Fluorinated Alcohols: Magic Reaction Medium and Promoters for Organic Synthesis

“…Later on, similar aza-(3 + 2) cycloaddition using α-halohydroxamates 36 as the precursor of aza-oxyallyl cation were reported by Jeffrey, [27] Wu [28] and Liao [29] (Scheme 12). By this means, highly functionalized pyrroloindolines 37 that are represented in large number of bioactive compounds could be assembled in simple operation.…”

Transition‐Metal‐Free Synthesis of N‐Hydroxy Oxindoles by an Aza‐Nazarov‐Type Reaction Involving Azaoxyallyl Cations

“…In 1993, the group of Kikugawa showed evidence for azaoxyallyl cation intermediates, but there had not been much progress until Jeffrey and co‐workers reported the first practical [4+3] cycloaddition involving azaoxyallyl cations . Very recently, the groups of Jeffrey and Wu, and ourselves reported a dearomative [3+2] cycloaddition of azaoxyallyl cationic intermediates. Our group has also explored the application of azaoxyallyl cations as synthons in synthetic approaches towards (±)‐minfiensine .…”