An Ireland-Claisen Rearrangement/Lactonisation Cascade as a Key Step in Studies Towards the Synthesis of (-)-Euonyminol:

Abstract

Progress towards the asymmetric total synthesis of (-)-euonyminol is described with the focus on the installation of the ­oxygenation pattern on the lower rim of the molecule. An Ireland-Claisen rearrangement/lactonisation cascade has been developed and studies towards further elaboration have uncovered an intriguing tunable diastereoselective α-bromination of the resulting γ-lactone.

Key words

Ireland-Claisen - Celastraceae - bromination - euonyminol - sesquiterpene

References and Notes

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  The example most similar to ours involves the α-bromination of an α-(-)-santonin derivative (compound 19, see Supporting Information) for which the stereochemistry of the product was assigned by NOE (see ref. 13h). We repeated this reaction under both their conditions (LiCPh₃, BrCH₂CH₂Br, 37% yield) and ours (TMSCl, LDA, NBS, 80% yield), obtained the same product 20 they report for both reactions, and confirmed the reported stereochemistry by a single crystal X-ray structure determination (see Supporting Information). Oxidation of lactone 19 also proceeded on the convex face to give α-hydroxylactone 21 (LDA, MoOPD, 62% yield; cf. Scheme  [4] ; see Supporting Information).

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14

Stereochemical assignments were made based upon NMR spectroscopic comparisons with bromolactones 9a and 15b for which X-ray structural data were obtained (see Supporting Information).

19

Product 18 was not fully characterised due to lack of material and this line of investigation has not been pursued further to allow verification of the stereochemistry at C-11.