Total Synthesis of (−)-Enigmazole B

Total synthesis of (−)-enigmazole B was achieved for the first time. Highlights of the present synthesis include an olefin cross-metathesis and hemiacetalization/intramolecular oxa-Michael addition sequence for accessing an (E)-configured enol tosylate, a Sonogashira cross-coupling to assemble all the carbon atoms of the target natural product, a remarkably chemo- and regioselective Au-catalyzed intramolecular alkyne hydroalkoxylation for the construction of the dihydropyran ring, and a Yamaguchi macrolactonization to close the 18-membered macrolactone skeleton.