A concise catalytic route to the marine sesquiterpenoids (-)-clavukerin A and (-)-isoclavukerin A

Using a combined organocatalytic/metal-catalyzed strategy, the enantiopure title hydroazulenes were prepared in only four steps from (S)- and (R)-citronellal, respectively. A catalyst-controlled diastereoselective Michael addition of these aldehydes to methyl vinyl ketone followed by chemoselective dibromoolefination and one-pot Wittig olefination/alkyne formation afforded the key dienynes that underwent regioselective domino metathesis to yield the target natural products. A combination of an organocatalytic Michael addition and a ruthenium-catalyzed dienyne metathesis allowed efficient access to the enantiopure title hydroazulenes from (S)- and (R)-citronellal, respectively, in only four steps.