Total Synthesis of (−)-Coriolin

Abstract

An efficient synthetic method for (-)-coriolin has been developed on the basis of a [3+2] cycloaddition reaction of a 1-(methylthio)-2-siloxyallyl cationic species and vinylsulfides. An enantiomerically pure C-ring unit was prepared through optical resolution of five-membered allyl ester 6b using a lipase. The first [3+2] cycloaddition reaction of C-ring unit (S)-7 gave bicyclic ketones 8 and 9, which were easily converted into vinyl sulfide 11. Stereoselective construction of the A-ring was achieved by the second [3+2] cycloaddition reaction of the BC-ring unit. New methods for introduction of the oxygen functional groups to the triquinane skeleton were also developed for the last stages of the total synthesis. Thus, the C7 hydroxyl group was introduced by epoxidation of dienol silyl ether 17, and stereocontrolled construction of the spiro epoxide moiety was accomplished on the basis of a Darzens-type reaction.

(3+2)-Cycloaddition Reactions of Oxyallyl Cations

“…13,14 As shown in Scheme 4, the ABC triquinane ring system of coriolin was constructed via two successive (3+2)-cycloaddition reactions. Treatment of benzyl ether 16 with vinyl sulfide 6 in the presence of EtAlCl 2 provided a 1:1 mixture of annulated products 17 and 18 in diastereomerically pure forms.…”

Synthesis of the Epimeric Secosteroids Strophasterols A and B

“…[19] After considerable experimentation, we found that exposure of 17 to hydrogen in the presence of palladium on carbon in hexane gave 7 exclusively (95 %i solated yield), [20] while hydrogenation with Crabtreesc atalyst in CH 2 Cl 2 afforded as eparable 1.7:1 mixture of 22-epi-7 and 7,favoring the former isomer. Although 22-epi-7,w hich we set as ap recursor to 2,c ould also be secured (20 %yield through 2steps from 8)byconducting the dithioacetalization at room temperature,w es ought ab etter way to give 22-epi-7 preferentially and examined the stereoselectivity of the hydrogenation of trisubstituted cyclopentene 17 prepared from 8 via thioenol ether 16.…”

Access to Sulfides through Free Radical Reaction of Vinyl Halides with Thiols

“…[5] Vinyl sulfides are popular fragments utilized to prepare ketones, [6] olefins, [7] diaryl sulfides, [8] cyclobutyl sulfides, [9] and cyclopentyl sulfides. [10] Alkyl sulfides are generally used as sulfoxide precursors. [11] Sulfide derivatives are also widely used as organic materials in polymer [12] and molecular electronics.…”