A facile synthesis of (6S,1′S)-(+)-hernandulcin and (6S,1′R)-(+)-epihernandulcin

A facile total synthesis of (+)-hernandulcin () was accomplished from (−)-isopulegol in 6 steps with 15% overall yield. Epoxidation of (−)-isopulegol with m-chloroperbenzoic acid followed by opening of the epoxide with prenyl Grignard afforded the tertiary alcohol with correct C-6 and C-1′ stereochemistry as a major product. Oxidation of the secondary alcohol in compound to the ketone was accomplished in high yield by using TPAP and N-methylmorpholine N-oxide. Conversion of the ketone to α,β-unsaturated ketone via organoselenium intermediate gave (+)-hernandulcin (). This method was also successfully applied to the synthesis of (+)-epihernandulcin ().