Total Synthesis of - -Papuamine

Abstracted with permission from J. Org. Chem., 1996,61, 700 1996 American Chemical Society 

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Applications of /3-Tosylethylamine. Borzilleri and Weinreb used TSE amine (3) in an imino-ene cycUzation for the total synthesis of (—)-papuamine. Exposure of the allenylsilane aldehyde 8 to amine 3 in the presence of SnCLj or under thermal conditions generates the corresponding imine, which undergoes stereospecific cyclization to afford the TSE aminoalkyne 9 following workup with TBAF (eq 3). The aminoalkyne 9 was converted to the... 

Barrett, A.G.M., Boys, M.L., and Boehm, T.L. (1994) Total synthesis of (+)-papuamine determination of the absolute stereochemistry of the natural product J. Chem. Soc. Chem. Commun., 1881-1882. 

Deshpande [74], has carried out carbon-carbon bond formation on a solid support using a polymer-supported aryl iodide and vinyl (or aryl) tins. In the area of natural-product synthesis. Overman and co-workers have carried out total syntheses of (—) and (+)-strychnine which include an aryltin/CO/alkenyltin coupling step [75] (a technique introduced earlier by Stille [1]). Very recently, Heathcock and co-workers have reported total syntheses of (—)-papuamine and (—)-haliclonadiamine which include a key step in which a 1,3-diene unit is constructed by coupling two alkenyltin moieties thus reaction (Scheme 4-27) only proceeds in the presence of copper (I) iodide [76]. 

These novel structures, together with their biological aspects, make this family of alkaloids a highly attractive target for total chemical synthesis. Several approaches for the total synthesis of manzamine A have been published, although its synthesis has not yet been achieved. Likewise, in recent years other compounds such as papuamine, haliclonadiamine, saraine or cyclostellamine C have been candidates for total synthesis. 

Allenylsilanes 159 (Eq. 13.53) and 161 (Eq. 13.54) differ in the axial stereochemistry of the allene function. In each case, formation of the benzyl imine, followed either by treatment with tin(IV) chloride in benzene at room temperature or heating in toluene, leads to diastereomeric products 160 and 162 [63], Significantly, there is no crossover, pointing to a concerted (or fast, stepwise) process. Since the absolute stereochemistry of the allenylsilanes is easily controlled, the methodology is ideal for applications in total synthesis. Weinreb and co-workers have used the reaction for his synthesis of the marine natural product (-)-papuamine. 

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