ALPHA-CARBONYL RADICAL CYCLIZATION APPROACH TOWARD ANGULAR TRIQUINANES - TOTAL SYNTHESIS OF ENANTIOMERICALLY PURE (-)-5-OXOSILPHIPERFOL-6-ENE

An alpha-carbonyl radical cyclization approach toward synthesis of ang ular triquinanes is described. As a model study, conjugate addition of 4-(trimethylsilyl)-3-butynylmagnesium chloride to enone 7 followed by trapping of the enolate with chlorotrimethylsilane gave trimethysilyl enol ether 8. Iodination of 8 with a mixture of NaI and m-CPBA afford ed iodo ketone 6. Radical cyclization of 6 effected by Bu3SnH and AIBN gave 5. Epoxidation of 5 with m-CPBA yielded epoxy ketone 9. Desilyla tion and rearrangement of 9 by formic acid gave aldehyde 4. Aldol cond ensation and dehydration furnished angular triquinane skeleton 3. Tota l synthesis of (-)-5-oxosilphiperfol-6-ene (1) was accomplished in 12 steps starting from keto ester 14 based on this route. Conjugate addit ion of 3-hexynylmagnesium bromide to chiral ester 13 followed by treat ment with chlorotrimethylsilane gave intermediate 15. Iodination of 15 with a mixture of NaI and m-CPBA gave alpha-iodo ester 12. Intramolec ular radical cyclization of 12 gave ester 11. Reduction of 11 by LiAlH 4 yielded alcohol 16. On treatment with m-CPBA, alcohol 16 was convert ed to the corresponding epoxide 17, which was subjected to the epoxy-k etone rearrangement using BF3 etherate as a catalyst to give ethyl ket one 18. Subsequent oxidation of 18 with PCC afforded aldehyde 10. Intr amolecular aldol condensation of 10 yielded tricyclic compound 19. Met hylation of 19 gave 20. Conjugate addition of lithium dimethylcuprate to 20 followed by trapping of the resulting enolate with chlorotrimeth ylsilane gave 21. Oxidation of 21 by DDQ afforded enantiomerically pur e (-)-5-oxosilphiperfol-6-ene (1). Racemic (+/-)-1 was also synthesize d in the same manner in order to determine the optical purity of chira l product (-)-1. The gas chromatographic analysis with a chiral column proved that 1 has high enantiomeric purity. A single-crystal X-ray an alysis of 2,4-dinitrophenylhydrazone 22 was performed to unambiguously confirm the stereochemistry of 19.