Retro-[4+2]/Intramolecular Diels–Alder Cascade Allows a Concise Total Synthesis of Lucidumone

Abstract

Lucidumone is a recently isolated meroterpenoid displaying interesting biological activity. This natural product possesses a complex structure, including a bicyclo[2.2.2]octane possessing 6 contiguous stereogenic centers. Herein, we discuss strategies to solve this synthetic challenge. In particular, we developed a new method for the inverse electron-demand Diels–Alder cycloaddition between 2-pyrones and acyclic enol ethers, as a mean to obtain a ‘masked’ cyclohexadiene. This method allowed an expeditious enantioselective synthesis of (+)-lucidumone through a retro-[4+2]/intramolecular Diels–Alder reaction cascade.

1 Introduction

2 Retrosynthetic Considerations on the Bicyclo[2.2.2]octane

3 Development of a Methodology for Enantioselective IEDDA Cycloadditions

4 Enantioselective Total Synthesis of (+)-Lucidumone

5 Conclusion

Key words

total synthesis - meroterpenoid - Diels–Alder - enantioselectivity - diastereoselectivity - catalysis - cascade reactions

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