Enantioselective total synthesis of (-)-FR182877

An enantioselective total synthesis of (−)-FR182877 is described. This total synthesis features 1) the one-pot stereoselective tandem IMDA-IMHDA reaction which affords the tetracyclic compound including the ABCD ring system of (−)-FR182877 with the correct new seven stereogenic centers, 2) the palladium-mediated 7-exo-trig intramolecular Heck reaction for the construction of the highly strained seven-membered F-ring, and 3) the iridium-mediated isomerization of the allylic alcohol to the α-methyl ketone followed by epimerization and the stereoselective reduction to furnish all the stereogenic centers of (−)-FR182877.