Total Synthesis of (+)-Mutilin: A Transannular [2+2] Cycloaddition/Fragmentation Approach

A new and enantioselective total synthesis of the diterpenoid (+)-mutilin is described. Following a Claisen rearrangement approach to construct the 6,9-bicycle, a transannular [2+2] photocycloaddition and the ensuing ring-opening reaction were implemented to forge the characteristic 5–6–8 propellane-like skeleton. Subsequent late-stage alkylations and reduction completed the synthesis.