Issue 35, 2020

Total synthesis of endiandric acid J and beilcyclone A from cyclooctatetraene

Abstract

The endiandric acids are classic targets in natural product synthesis. The spectacular 8π/6π-electrocylisation/intramolecular Diels–Alder (8π/6π/IMDA) reaction cascade at the heart of their biosynthesis has inspired practitioners and students of pericyclic chemistry for nearly forty years. All previous synthetic approaches have sought to prepare a linear tetraene and thereby initiate the cascade. In this communication we demonstrate the use of cyclooctatetraene to rapidly intercept the 8π/6π/IMDA cascade at the cyclooctatriene stage. Endiandric acid J and beilcyclone A are prepared for the first time in six and five steps, respectively. The strategy features a tactical overall anti-vicinal difunctionalisation of cyclooctatetraene through SN2′ alkylation of cyclooctatetraene oxide followed by an intriguing tandem Claisen rearrangement/6π-electrocyclisation from the corresponding vinyl ether. This rapidly constructs an advanced bicyclo[4.2.0]octadiene aldehyde intermediate. Olefinations and intramolecular Diels–Alder cycloadditions complete the syntheses. This establishes a short and efficient new path to the endiandric acid natural products. DFT modelling predicts thermal racemisation of bicyclo[4.2.0]octadiene intermediates, dashing hopes of enantioselective synthesis.

Graphical abstract: Total synthesis of endiandric acid J and beilcyclone A from cyclooctatetraene

Supplementary files

Article information

Article type
Edge Article
Submitted
01 Jun 2020
Accepted
16 Jul 2020
First published
29 Jul 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2020,11, 9421-9425

Total synthesis of endiandric acid J and beilcyclone A from cyclooctatetraene

O. Yahiaoui, A. Almass and T. Fallon, Chem. Sci., 2020, 11, 9421 DOI: 10.1039/D0SC03073B

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