Daphniphyllum alkaloids. 11. Biomimetic total synthesis of methyl homosecodaphniphyllate. Development of the tetracyclization reaction

A biomimetic total synthesis of (±)-methyl homosecodaphniphyllate has been developed. The synthesis starts with a triply convergent, tandem Michael addition-enolate alkylation, wherein amide 9, enoate 7, and alkyl iodide 5 are assembled in essentially quantitative yield to obtain compounds 13, 14, and 15. The major isomer 13 is converted in three steps into a 1:1 mixture of diols 18a and 18b. These diols are subjected to a two-step process involving Swern oxidation and treatment of the resulting dialdehyde sequentially with ammonia and acetic acid