# An Unexpected Isomerization for the Total Synthesis of Daphnepapytone A

## TL;DR

The paper describes a high-yielding synthesis of daphnepapytone A using unexpected isomerization to improve yield.

## Contribution

A novel isomerization strategy is introduced to convert unwanted byproducts into the desired compound during synthesis.

## Key findings

- A trisubstituted chiral cyclopentenone was efficiently synthesized via reductive cleavage.
- A serendipitous aldehyde epimerization improved the yield by converting unwanted exo-epimer into the endo-enantiomer.
- The final natural product was obtained in fewer steps using a second Pauson–Khand reaction.

## Abstract

We report a high-yielding total synthesis
of sesquiterpenoid
daphnepapytone
A from (S)-glycidol. The groundwork for the synthesis
is laid via reductive cleavage of a bicyclic Pauson–Khand-derived
cyclopentenone ether, giving efficient access to a trisubstituted
chiral cyclopentenone which is difficult to obtain by other means.
To introduce the cyclobutane motif, the enone was irradiated in the
presence of allene gas, yielding the unwanted exo-cyclobutane at worst
and 1:1 mixtures of the endo- and exo-product at best. A serendipitous
epimerization of an aldehyde in the following steps converted the
unwanted exo-epimer into the endoenantiomer, which significantly improved
the final yield. The final cage was connected with a second Pauson–Khand
reaction, requiring only one more step to yield the natural product.