Pyrone Diels-Alder Routes to Indolines and Hydroindolines: Syntheses of Gracilamine, Mesembrine, and Δ7-Mesembrenone

Pei Gan, Myles W. Smith, Nathaniel R. Braffman, Scott A. Snyder

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Although the Diels-Alder reaction has long been utilized for the preparation of numerous heterocycles, opportunities to extend its power remain. Herein, we detail a simple, modular, and robust approach that combines various amines regioselectively with 4,6-dichloropyrone to create substrates which, under appropriate conditions, can directly deliver varied indolines and hydroindolines through [4+2] cycloadditions with substitution patterns difficult to access otherwise. As an initial demonstration of the power of the strategy, several different natural products have been obtained either formally or by direct total synthesis, with efforts toward one of these - the complex amaryllidaceae alkaloid gracilamine - affording the shortest route to date in terms of linear step count. Pyrone-technics: A simple, robust, and readily modifiable strategy involving [4+2]/retro-[4+2]/hydrolysis cascade sequences generates a range of indolines and hydroindolines from 4,6-dichloropyrone and appropriate amines. A 10 step synthesis was achieved of a ketone previously accessed in 15 steps, thereby accomplishing the shortest formal total synthesis of the alkaloid gracilamine. Teoc=2-(trimethylsilyl)ethoxycarbonyl.

Original languageEnglish (US)
Pages (from-to)3625-3630
Number of pages6
JournalAngewandte Chemie - International Edition
Volume55
Issue number11
DOIs
StatePublished - Mar 7 2016
Externally publishedYes

Fingerprint

Pyrones
Alkaloids
Amines
Amaryllidaceae Alkaloids
Cycloaddition
Biological Products
Ketones
Hydrolysis
Substitution reactions
Demonstrations
Substrates
mesembrenone
gracilamine
mesembrine
indoline

Keywords

  • alkaloids
  • cascade reaction
  • Diels-Alder reaction
  • natural products
  • total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Pyrone Diels-Alder Routes to Indolines and Hydroindolines : Syntheses of Gracilamine, Mesembrine, and Δ7-Mesembrenone. / Gan, Pei; Smith, Myles W.; Braffman, Nathaniel R.; Snyder, Scott A.

In: Angewandte Chemie - International Edition, Vol. 55, No. 11, 07.03.2016, p. 3625-3630.

Research output: Contribution to journalArticle

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