Total synthesis of the pentacyclic diterpenoid tropone hainanolidol

The total synthesis of the unusual diterpenoid tropone, hainanolidol (1), d iscovered in the bark of the yew species, Cephalotaxus hainanensis, has bee n completed in 26 steps from 3,5-dimethylanisole. The intramolecular cyclop ropanation reaction of the aryl ring in (30) by means of the rhodium mandel ate-catalysed reaction of the diazoacetyl function was used to assemble the 5/7 ring system of (31), at the same time elaborating a cycloheptatriene m oiety that could be transformed subsequently to the tropone functionality i n the target molecule. While removing the acetal protecting group from (31) an unexpected Mukaiyama-type aldol process was induced by ZnBr2, affording (32), the structure of which was determined by X-ray analysis. With greate r care, the aldehyde (33) could be obtained and the desired carbocyclic rin g system completed by means of a base-catalysed aldol reaction with the new ly formed hydroxyl being employed subsequently in the formation of the delt a -lactone function in (35). Desilylation, reduction of the C-10 carbonyl f unction and brief exposure to acid finally afforded (1). This last step too k advantage of the stability of the tropylium ion (40) to provide a 'thermo dynamic sink' for the reaction outcome. The synthesis of (1) also constitut es a formal synthesis of the troponoid ether, harringtonolide (2), since th is compound had been obtained previously from (1) by means of a transannula r oxidation process. Methodology for the assembly of the tropone moiety in (1) and (2) was modelled on the simpler bi- and tricyclic systems, (13) and (22), respectively.