Stereoselective Total Synthesis of (±)-Peribysin E

Radical cyclization of iodoketone 3 afforded cis-hydrindanone 8. Compound 8 was converted into key intermediate 5 via conventional
transformations. Annulation of a spiro-lactal unit to 5 was pursued with three different approaches. In the first approach,
radical cyclization of propargyl ester 17 provided spiro-lactone 18 with an undesired stereochemistry. Attempts to invert the
stereochemistry at the spiro-center via retro-aldol and aldol condensation
of compound 20 failed. In the second approach, key intermediate 5 was transformed into 23. Acylation of compound 23 gave 24 as a single diastereomer with the
desired stereochemistry but in low yield. NBS bromination of 24 followed by lactone formation gave 26 in low
yield. Alternatively, allylic oxidation of 24 with SeO2 followed by lactonization gave 26 also in low
yield. Finally, a third approach employing a semipinacol-type rearrangement
of epoxy-alcohol 33 gave aldehyde 34 with
the desired stereochemistry. Treatment of compound 34 with HCl in MeOH effected spiro-lactal formation and provided (±)-peribysin
E. The overall yield of our synthesis is 3.2% from 2-methylcyclohenen-1-one.