TOTAL SYNTHESIS OF (-)-DENDROBINE VIA ALPHA-CARBONYL RADICAL CYCLIZATION

An efficient total synthesis of enantiomerically pure (-)-dendrobine ( 1) is accomplished based on an ol-carbonyl radical cyclization reactio n. (S)-carvotanacetone (6) was converted to bicyclic acetal-enone 4 in five steps. CuI-mediated conjugate addition of 4-(trimethylsilyl)-3-b utynylmagnesium chloride to 4 followed by treatment with TMSC1 afforde d trimethylsilyl enol ether 10. Iodination of 10 with NaI and m-CPBA g ave iodoketone 3. Intramolecular radical cyclization of 3, effected wi th Bu3SnH and AIBN, furnished tricyclic ketone 2. Removal of the TMS g roup of 2 and oxidation of the resulting cyclic acetal 12 with m-CPBA and BF3 etherate gave peroxy compound 13. Compound 13 was treated with DBU to yield lactone 14. Hydroboration of 13 with basic H2O2 oxidatio n gave diol 17. Conversion of 17 to the corresponding azido alcohol 19 followed by Jones oxidation furnished azido ketone 20. Treatment of 2 0 with PPh3 followed by reduction with NaBH3CN afforded amine 21. Crud e amine 21 was methylated to give enantiomerically pure (-)-dendrobine (1).