Convergent synthesis of potent COX-2 inhibitor inotilone

The first synthesis of potent COX-2 inhibitor inotilone is reported. The convergent route features a Mukaiyama aldol condensation that generates the target without the use of protecting groups or a separate dehydration step. The approach also highlights a superior regioselective preparation of 1-bromo-2,4-pentanedione involving a bis(silyl enol ether) and NBS.