Abstract
Azadirachtin (1), which was isolated in 1968 from the seeds of the Indian neem tree, exhibits strong antifeedant and repellent activities against insects. Toward the total synthesis of 1, we designed a new strategy for constructing the highly hindered quaternary C8 carbon atom via an addition reaction of an allylborane with an aldehyde. Enol silyl ether 14 was synthesized from enone 13 through the stereoselective conjugate addition reaction with a vinylcuprate. After construction of the A ring by RCM, cyclic acetal 17 was obtained by hydrogenation of 16 in MeOH and subsequent treatment with TsOH. Stereoselective alkylation of ester 17 followed by hydrolysis produced hydroxy ketone 18 which was then converted to an iodo acetal. Treatment with KO'Bu effected stereoselective construction of the C ring, and the product was transformed into diene 23 in three steps. The reaction of diene 23 with BH_3・THF followed by pinacol resulted in formation of the undesired allylboranes 24 and 25 through hydroboration at the C7-C8 double bond. On the other hand, the hydroboration reaction of dienol triflate 26 afforded allylborane 27 which was converted to 28 through a cross coupling reaction. The key addition reaction of allylborane 28 with aldehyde 29 proceeded smoothly to afford propargyl alcohol 30 as a single isomer. Finally, the E ring was constructed by using the Pd-catalyzed Nazarov cyclization reaction of en-yne 34 giving rise to a cyclopentenone derivative 35.
