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. 2025 Jun 1:178:134619.
doi: 10.1016/j.tet.2025.134619. Epub 2025 Mar 25.

Studies toward the synthesis of yaretol: an unexpected rearrangement en route to the tricyclic core

C Elizabeth Adams  1 , Steven D Townsend  1
Affiliations

Studies toward the synthesis of yaretol: an unexpected rearrangement en route to the tricyclic core

C Elizabeth Adams et al. Tetrahedron. .

Abstract

Yaretol is a polycyclic norditerpene constituting a structurally distinct class of terpene natural products isolated from Azorella madreporica which, to date, has not been accessed via total synthesis. Herein, we report our synthetic efforts toward a key intramolecular Diels-Alder furan (IMDAF) cycloaddition to construct the carbon framework. We discuss our efforts toward the cycloaddition wherein undesired aromatization and unanticipated rearrangement of the cycloadduct are observed.

Keywords: cycloaddition; furan Diels-Alder; total synthesis; yaretol.

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Figures

Figure 1.
Figure 1.
Structures of yaretol and representative mulinane and azorellane natural products.
Scheme 1.
Scheme 1.
Retrosynthetic analysis of yaretol (1A).
Scheme 2.
Scheme 2.
Failed attempts to install furan via enolate alkylation.
Scheme 3.
Scheme 3.
Unsuccessful attempt to directly alkylate 2-methylfuran.
Scheme 4.
Scheme 4.
Synthesis of Diels-Alder precursors 3 and 26.
Scheme 5.
Scheme 5.
A) Proposed formation of rearrangement product 31. B) Rationalization of diastereoselective formation of 24.
Scheme 6.
Scheme 6.
Synthesis and attempted Diels-Alder of bromo-substituted addend.
See this image and copyright information in PMC

References

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