Enantioselective synthesis of the tricyclic core of (−)-FR901483

An enantioselective synthesis of the tricyclic core structure of the immunosuppressant natural product (−)-FR901483 has been achieved. A palladium-catalysed (Pd2(dba)3, Xantphos, KOPh) intramolecular enolate alkenylation reaction was used as the key ring forming step for the construction of the bicyclo-[3,3,1]-azanonane ring system. An alkylidene carbene 1,5-CH insertion reaction was used to construct the nitrogen-bearing stereocentre in the vinyl bromide cyclisation precursor.