P-12 新規ラジカル環化反応の開発(ポスター発表の部)

抄録

During the course of our program directed towards the total synthesis of diterpenoid quinones with interleukin-1 inhibitory activities, we found the novel and fascinating free-radical mediated cyclization reactions which led to the formation of tricyclic spiro compounds or bicyclo[5.4.0]undecanones. 1. Development of Radical Cascade Reaction Treatment of 7a,b with tri-n-butyltinhydride in the presence of AIBN in refluxing toluene provided the spiro ketones 8a,b in 57% and 51% yield, respectively. The mechanism of formation was speculated by deuterium incorporation experiments and calculations. 2. Free-Radical Mediated Ring Expansion Reaction In contrast to 7a,b, the radical reaction of the bicyclic keto thiocarbonate 17 afforded the bicyclo[5.4.0]undecanone 21, which would be produced via cyclopropyloxy radical 23 or acyl radical 24 intermediate, in 59% yield. 3. Formal Total Synthesis of (+)-Confertin Employing the Ring Expansion Reaction Exposure of 36, derived from the chiral enone 32, to the same conditions as before gave the bicyclo[5.3.0]decanone 37, which was converted to the hydroxy ketone 38. The spectral properties of 38 were identical to those of the authentic material reported in the total synthesis of racemic confertin by Heathcock. 4. Alternative Ring Expansion Reaction and Synthesis of (+)-O-Methylpodocarpic Acid The radical reaction of 50 having the different substitution pattern on the phenyl ring afforded unexpectedly the ring expanded ketone 52 as the major product along with spiro compound 51. This results was rationalized by calculations of the energy difference between the chair and the boat conformation of the intermediary radicals. Additionally, the chiral alcohol 44, a synthetic intermediate of 50, was successfully converted to the O-methylpodocarpinol 47, which had been led to (+)-O-methylpodocarpic acid 48 by Snider. Furthermore, the radical reaction of 54 involving the epimeric quaternary carboncenter appeared to give exclusively the ring expanded product 55.