AI Article Synopsis
- - The research focuses on synthesizing endiandric acids, known as key targets in natural product chemistry, using a unique reaction cascade called 8π/6π-electrocyclisation/intramolecular Diels-Alder (8π/6π/IMDA).
- - The study introduces a method utilizing cyclooctatetraene to speed up the synthesis process, achieving the production of endiandric acid J and beilcyclone A in just six and five steps, respectively.
- - While the synthesis shows promise for efficiency, DFT modeling indicates potential challenges with racemisation in intermediates, making enantioselective synthesis difficult.
Article 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 -vicinal difunctionalisation of cyclooctatetraene through S2' 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161681 | PMC |
| http://dx.doi.org/10.1039/d0sc03073b | DOI Listing |
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Article Synopsis
- - The research focuses on synthesizing endiandric acids, known as key targets in natural product chemistry, using a unique reaction cascade called 8π/6π-electrocyclisation/intramolecular Diels-Alder (8π/6π/IMDA).
- - The study introduces a method utilizing cyclooctatetraene to speed up the synthesis process, achieving the production of endiandric acid J and beilcyclone A in just six and five steps, respectively.
- - While the synthesis shows promise for efficiency, DFT modeling indicates potential challenges with racemisation in intermediates, making enantioselective synthesis difficult.
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