A novel approach to the taxane BC ring system through formation of alpha-ketol by oxidative removal of the phenylsulfonyl group with subsequent in situ oxidation.
Cis-fused bicyclo[6.4.0]dodecene 11 was converted into taxane BC ring system 21 in three steps; transformation of the phenylsulfonyl group to an alpha-hydroxy carbonyl group by the treatment with potassium hexamethyldisilazide (KHMDS) and triethyl phosphite under oxygen atmosphere, followed by reductive elimination of the hydroxyl group of alpha-ketol moiety, and inversion of ring juncture. Epimerization of the sulfonyl group of 11 was indispensable for the first oxidation process (17 --> 18) and the second oxidation of 12 leading to hydroxylation at the alpha-position of the carbonyl group proceeded with high regio- and stereoselectivity to give 13. On the other hand, reaction of the cross-conjugated compound 5 with KHMDS at 0 degrees C brought about a complete reorganization of molecular framework to provide the compound 7 in which the five-membered ring and the conjugated seven-membered ring were connected through a single bond.
Fujishima
H
H
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan.
Takeshita
H
H
Toyota
M
M
Ihara
M
M
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D013441:Sulfinic Acids / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry; D043823:Taxoids
D001952:Bridged-Ring Compounds; D013441:Sulfinic Acids; D013450:Sulfones; D043823:Taxoids; C080625:taxane