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[摘要]：An efficient stereocontrolled route to the spirocyclic perhydrohistrionicotoxin deriv. (?-2,7,8-epi-PHTx (I) is described. The reaction of 2-butyl-3-(methoxymethoxy)cyclohexanone oxime with 2,3-bis(phenylsulfonyl)-1,3-butadiene gives rise to a 7-oxa-1-azanorbornane cycloadduct in high yield. The formation of the bicyclic isoxazolidine arises from conjugate addn. of the oxime onto the diene to give a transient nitrone which then undergoes an intramol. dipolar cycloaddn. Treatment of the cycloadduct with 5% Na/Hg results in reductive nitrogen-oxygen bond cleavage to furnish an azaspiro[5.5]undecane. Elaboration to the dihydropyridin-4(1H)-one was followed by stereoselective conjugate addn. using n-pentyl cuprate to give an azaspirocycle. The stereochem. of the product was deduced from an X-ray crystal structure of the corresponding N-tosylhydrazone deriv. The dominant factor controlling the stereochem. of the conjugate addn. is the A(1,3)-strain present in the planar vinylogous amide. A stereoelectronically preferred axial attack by the organocuprate at the b-position leads to the obsd. diastereoselectivity. The azaspirocycle was transformed into I in five addnl. steps. Utilizing this tandem conjugate addn./dipolar cycloaddn. cascade, we have also successfully synthesized an azaspiro[5.5]undecane, which had previously been converted into (?-perhydrohistrionicotoxin, thereby completing a formal total synthesis of this alkaloid. |
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