Silphiperfolene

The presence of a tetrasubstituted C=C bond in the A-ring of (—)-silphiperfolene provides a logical starting point from where to commence retrosynthetic disassembly. It was Fraser-Reid s view that the option of further functionalisation followed by disconnection was the more... 

Scheme 10.1 Fraser-Reid s retrosynthetic analysis for (—)-silphiperfolene.

Mechanistic analysis of the Fraser-Reid (—)-silphiperfolene synthesis... 

For example, ( )-hirsutene, a member of the triquinane class of natural products, has been prepared by tandem radical cyclization as shown in equation 132801. Also, in a key step in the synthesis of silphiperfolene, the tricyclic ketal precursor oxosilphiperfolene was generated by a tandem cyclization process (equation 133)805. The desired enantiomer was generated in a 5 2 excess over the unwanted one. 

Figure 3.9. Natural products synthesized using Meyers s bicyclic lactam methodology cuparenone [100], mesembrine [101], abscisic acid [102], capnellene [102], silphiperfolene [94], and aspidospermine [103].

Fraser-Reid s group have described further examples of the use of serial radical cyclization to prepare di- and triquinane natural products. The previously-reported intermediate (4) (Vol. 23, p. 264) has been ring-opened by a Vasella-Bernet reaction, and hence converted to the triquinane (5) with the silphinene skeleton (Scheme 2). Similar initial steps were involved in the conversion of (6) into silphiperfolene (7), and to transform (8) (Vol. 23, p. 265) into (-)-a-pipitzol (9) (mannose carbons numbered). ... 

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