Ether formation by intramolecular attack of hydroxy on cyclopropyl rings: a model for the formation of the tetrahydrofuran moiety in the diterpenoid, harringtonolide

Abstract

The electrophile induced opening of a cyclopropyl ring with concerted intramolecular addition of a hydroxymethyl group in a number of tricyclo[3.2.2.0^2,4]nonene alcohol derivatives has been studied with a view to establishing a procedure for the formation of the tetrahydrofuran ring in the diterpenoid tropone 4. Treatment of the tricyclo[3.2.2.0^2,4]nonene diol 15 with H₃PO₄, for example, furnishes diether 19, the structure of which has been determined by X-ray crystallography. This conversion is shown to involve sequential 1,2-bond shifts, rather than direct attack, however, while acid treatment of the saturated diol 16 leads to rearrangement of the carbon skeleton. Nevertheless, mercuric induced opening of the cyclopropyl ring in either 15 or 16 proceeds with direct ether formation as planned and in good yield; mercury is removed from the products by simple stannane reduction.