A Synthetic Approach to the Quassinoids

Article abstract of DOI:10.1021/jo00192a004

A synthetic route to the quassinoids has been developed.Two-stage annelation of 2-methylcyclohexanone with 1-chloro-3-pentanone gives tricyclic dienone 9 (60percent), which is oxidized by acetyl chromate in acetic acid to give dienedione 27 (80percent).Bisketalization of this material followed by hydrolysis of the conjugated enone ketals provides monoketal 30 (77percent), along with recovered 27.Ring C of 30 is functionalized by the Stiles and Reich methods to obtain the unsaturated keto ester 33 (73percent).The latter material reacts with ketene acetal 35 at 5-6 kbar and room temperature to give an adduct that is desilylated by treatment with aqueous KF; keto diester 39 is produced in 95percent yield.Epoxidation of 39 occurs smoothly with m-CPBA to give 46 (88percent), which is converted into allylic alcohol 40 by the two-step Sharpless procedure (78percent).Finally, pyridinium chlorochromate induces solvolytic cyclization of 40, affording 41 in 55percent yield.In the course of the investigation, it was also discovered that β-keto ester 46 is oxidized by m-CPBA to 47 in quantitative yield.