Enantioselective Synthesis of the Dimeric Pyranonaphthoquinone Core of the Cardinalins Using a Late-Stage Homocoupling Strategy

Abstract

The enantioselective synthesis of a dimeric pyranonaphthoquinone closely related to the cardinalins is described. Whilst attempts to effect a double Hauser–Kraus annulation of enone5 were unsuccessful using both bis-phthalide 4 and bis-sulfone21, a single annulation of cyanophthalide28 with enone5 furnished functionalised naphthalene31. Suzuki–Miyaura homocoupling of the aryl triflate 29 derived from 31 effected a late-stage construction of the biaryl bond and facilitated access to the biaryl 3. Double stereoselective lactolreduction installed the 1,3-cis stereochemistry of the pyran rings and a final double oxidative demethylation step furnished model dimer 1, completing the enantioselective synthesis of a dimeric pyranonaphthoquinone bearing the core structure of cardinalin 3.