Total Syntheses of (±)-Cephalotaxine and (±)-8-Oxocephalotaxine

A synthesis of (±)-cephalotaxine (1) was obtained based on a novel oxidative rearrangement of the bicyclic enamide 5 to the spirocyclopentanone lactam 20. The overall yield from keto ester 6 and amine 7 was 28%, in nine steps, or 41% in ten steps. Double-bond isomerization of minor side product ene lactam 9, with formation of the key ene lactam intermediate 5, increased the overall yields of the synthesis to 45% (nine steps) or 66% (ten steps). The racemate of the natural product 8-oxocephalotaxine (40) was obtained in an alternative last step by a selective reduction of the keto lactam 39.