Stereoselective Total Synthesis of Copa and Ylango Sesquiterpenoids: (+)-Copacamphor, (+)-Copaborneol, (+)-Copaisoborneol, (−)-Ylangocamphor, (−)-Ylangoborneol, (−)-Ylangoisoborneol

Abstract

Efficient, stereoselective syntheses of the tricyclic sesquiterpenoids (+)-copacamphor (3), (+)-copaborneol (4), (+)-copaisoborneol (5), (−)-ylangocamphor (6), (−)-ylangoborneol (7), and (−)-ylangoisoborneol (8) are described. Conversion of the keto acetate 9 (previously synthesized from the dione 1) into the keto tosylate 17 was accomplished via an eight-step sequence. Intramolecular alkylation of 17 afforded, in high yield, (+)-copacamphor (3), which had previously been converted into the corresponding alcohols 4 and 5 by Kolbe-Haugwitz and Westfelt. Alkylation of the enolate anion of the bicyclic dione 2 with 2-bromopropane in hexamethylphosphoramide gave mainly the O-alkylation product 19. Conversion of 19 into the keto mesylate 29 was carried out in 5 synthetic steps. Intramolecular alkylation of 29 afforded (−)-ylangocamphor (6). Reduction of the latter with calcium in liquid ammonia gave (−)-ylangoborneol (7), while reduction with lithium aluminum hydride yielded (−)-ylangoisoborneol (8).

Tricyclic Sesquiterpenes from Marine Origin

“…Its ozonolysis, subsequent oxidation, and methylenation afforded compound 506 in 76% yield. A carbonyl intramolecular condensation of the latter then afforded the bicyclic compound 507 in 76% yield, and 8 more steps , were needed to deliver the alcohol 508 in 17.9% yield. Oxidation (Collin’s reagent), intramolecular Prins reaction (CF 3 CO 2 H), and subsequent oxidation (excess of Collin’s reagent) of the resulting alcohol group furnished compound 509 in 55% yield .…”

Synthesis of Functionalized Bicyclo[3.2.1]octanes and Their Multiple Uses in Organic Chemistry

“…The synthesis and the cyclization of chiral keto ester 99, derived from (+)carvomenthone, was extensively studied by Piers and collaborators. 60 Their strategy involves the formation of bicyclo[3.2.1]octane-1,3-dione 100 which serves as key starting synthon for the stereoselective total synthesis of copa and ylando sesquiterpenoids.…”

Synthesis of a novel series of tetracyclic opioid antagonists incorporating an 8-aminobicyclo[3.2.1]oct-6-ene sub-unit

“…These chlorides all had the same 'up' geometry, as observed in other simpler series, 4,5 and revealed consistently in proton NMR by a doublet at about 3.9-4.1 ppm for the -CHCl-proton with a vicinal coupling of 5.0 Hz to the bridgehead hydrogen. 18 Another feature of the cycloaddition is that the alkyne could, in principle, approach the cyclohexenyl ring from either face, i.e. syn or anti to the angular methyl group.…”