Total Synthesis of (−)-Dendrobine via α-Carbonyl Radical Cyclization

An efficient total synthesis of enantiomerically pure
(−)-dendrobine (1) is accomplished based on
an
α-carbonyl radical cyclization reaction.
(S)-carvotanacetone (6) was converted to
bicyclic acetal-enone 4 in five
steps. CuI-mediated conjugate addition of
4-(trimethylsilyl)-3-butynylmagnesium chloride to 4 followed
by treatment
with TMSCl afforded trimethylsilyl enol ether 10.
Iodination of 10 with NaI and m-CPBA gave
iodoketone 3.
Intramolecular radical cyclization of 3, effected with
Bu3SnH and AIBN, furnished tricyclic ketone
2. Removal of
the TMS group 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 14
with basic H2O2
oxidation gave diol 17. Conversion of 17 to
the corresponding azido alcohol 19 followed by Jones
oxidation furnished
azido ketone 20. Treatment of 20 with
PPh3 followed by reduction with NaBH3CN
afforded amine 21. Crude
amine 21 was methylated to give enantiomerically pure
(−)-dendrobine (1).