Acids scopadulcic

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Scheme 4. Overman s sequential Heck cyclization approach to the synthesis of the scopadulcic acids.

Schlosser s super base 615 f. Schmidt trichloroacetimidate glyco-sidation 528,531,537,556 Schwartz s reagent 606, 616 scopadulcic acid A 571 scopadulcic acid diterpenes 569 secocorrin 100, 122, 126 f., 130... 

Scheme 28. Domino Heck reaction for the total synthesis of (-)-scopadulcic acid A 129...

Scheme 8. Cu-Catalyzed asymmetric cyclopropanation used by Overman in the enantioselective total synthesis of scopadulcic acid A (1999).

The resulting stereoisomeric (6R, 8.S )-cyclohcptcnone 31 is used for the synthesis of (+)-scopadulcic acid A 32 as an enantiodivergent approach. 

Finally the methyl ester is cleaved with lithium n-propyl-mercaptide by nucleophilic displacement and the benzyl ether by conventional catalytic hydrogenolysis to furnish (-)-scopadulcic acid (1). 

The above described total synthesis features the first enantiodivergent approach to (+)- and (—)-scopadulcic acid A. The central transformations are the stereoselective carbonyl group reduction with (S)-Alpine Borane , the use of enolization stereoselection to dictate which enantiomer is produced, and the palladium-catalyzed bis-Heck cyclization which occurs with complete stereo- and regiocontrol to establish the scopadulan scaffold. 

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