33 水銀トリフラートを活用するタキサン骨格への生合成類似アプローチ(口頭発表の部)

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We have developed an efficient olefin cyclization agent mercury(II) triflate, Hg(OTf)_2, and applied to the syntheses of a variety of carbocyclic terpenoids. Recently we found that the Hg(OTf)_2 is formed almost instantaneously in acetonitrile as a colorless solution. When this freshly prepared Hg(OTf)_2 was treated with homogeranyl acetate (2) in acetonitrile, an organomercuric compound 3 that has a tetrasubstituted double bond was obtained selectively. Of course it corresponds to the A ring of taxol (1). Thus we designed to construct taxane skeleton from 3 according to a biomimetic entry. Although a tremendous number of synthetic studies toward taxol have been carried out, biomimetic routes have not been intensively studied. Although a reaction of homogeranyl acetate (2) with Hg(OTf)_2 in acetonitrile at-20℃ for 20min afforded organomercuric compounds 3, 4, 5, and 6 in a ratio of 78:16:3:3, a 92:8 mixture of 3 and 4 was obtained in 93% yield after 72h. Furthermore it was found that isomer due to the minor trisubstituted olefin was gradually transformed into tetrasubstituted olefin during the course of the synthesis. Thus the mixture of 3 and 4 was employed for next hydroxylation step leading to a ketone 7 after oxidation. Acetallization, hydrolysis of acetate, and Swern oxidation provided aldehyde 8. The olefinic isomer originated from 4 was completely disappeared at this stage. Alkylation to give 10 and following Red-Al reduction afforded E-olefin 11, and hydrolysis-oxidation sequence gave keto aldehyde 12. Low valent titanium promoted McMurry cyclization of the ketoaldehyde 12 in PhH-THF provided diols with bicyclo[9,3,1]-pentadecatriene skeleton 13 and 14 in 70% yield in 5:1 ratio. The stereochemistries of 13 and 14 were established by the NOESY NMR experiments of the derived carbonates 18 and 19, respectively. Since the minor diol 14 afforded single crystal, the structure was also confirmed directly.
天然有機化合物討論会の論文
1996-09-02

33 水銀トリフラートを活用するタキサン骨格への生合成類似アプローチ(口頭発表の部)

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