4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions.

Michael J Burns,Richard J K Taylor,Ian J S Fairlamb,Thomas O Ronson

doi:10.3762/bjoc.10.116

Abstract

Two mild and efficient strategies have been developed for the O-functionalisation of 4-hydroxy-6-alkyl-2-pyrones, by using them as nucleophilic partners in oxa-Michael additions and the Mitsunobu reaction. The reactions proceed in moderate to excellent yields on a range of substrates containing useful functionality. The reactions serve as practical and valuable synthetic methods to construct complex 2-pyronyl ethers, which are found embedded in a number of natural products.

Highlights

The 2-pyrone motif is a prevalent structural feature of many complex natural products and biologically active compounds [1,2]
A variety of alkylated 2-pyrones 3b–e were synthesised according to the method of Hsung and co-workers [18], in order to further explore the scope of the Mitsunobu process
The reactions have been shown to tolerate a range of different functional groups by virtue of the mild conditions employed, affording the desired products in moderate to excellent yields in the majority of cases

Summary

Introduction

The 2-pyrone motif is a prevalent structural feature of many complex natural products and biologically active compounds [1,2]. Perhaps because of, this varied reactivity, O-functionalisation reactions of 4-hydroxy-2-pyrones, to afford 2-pyronyl ethers (e.g., Scheme 1), remain almost entirely limited to reactions with methylating agents or simple alkyl or acyl halides. We recently published an example of the Mitsunobu reaction using the compound 4-hydroxy-6-methyl-2-pyrone (3a) [14].

Results

Conclusion