Concise total syntheses of (+)- and (−)-ar-macrocarpene

Abstract

Concise catalytic asymmetric total syntheses of both the enantiomers of aromatic sesquiterpenes, (+)-ar-macrocarpene (1) and (–)-ar-macrocarpene (ent-1) is featured in 4 steps, 66.0% overall yields from commercially available 5,5-dimethylcyclohexane 1,3-dione 13. The enantioenriched 5,5-dimethyl-3-(p-tolyl)cyclohexanone 10 is found to be the key intermediate, which was obtained from catalytic enantioselective p-tolylboronic acid addition onto enone 11 using Pd(II)-(S,S)-DUPHOS (ent-L5) in >99% ee. Finally, a Wolf-Kishner reduction of cyclohexanone 10 completes straightforward access to naturally occurring sesquiterpenoid, (+)-ar-macrocarpene (1).