The first asymmetric synthesis of the title compound 1 is described. The crucial step is a facile construction of the tricyclic lactone, the basic skeleton of 1, via aliene intramolecular cycloaddition. Methyl (R)-(-)-3-hydroxyhept-6-enoate (3) was converted into the (R)-propargyl ether 8 in six steps. Base treatment (t-BuOK/t-BuOH, 83°C) of 8 caused a smooth cyclization via the intramolecular Diels-Alder reaction of the allenyl ether intermediate to give 9, which on successive hydration and oxidation provided the lactone 10 as a mixture of diastereomers. Aromatization of 10 afforded a single product (11), which was subjected to the Wacker oxidation to give (R)-(+)-1.
ASJC Scopus subject areas
- Organic Chemistry