Total syntheses of (+̲)-Methyl cantabrenonate, (+̲)-Methyl epoxycantabronate, and (+̲)-Crinipellin B

• Main Author: Renaud, Johanne
• Language: English
• Published: 2008
• Online Access: http://hdl.handle.net/2429/1913

The syntheses of two structurally related target compounds, (±)-methyl cantabrenonate(13) and (±)-methyl epoxycantabronate (14) are described in the first part of this thesis, while the preparation of the naturally occurring crinipellin B (15) is discussed in the second part of the thesis. Two methylenecyclopentane annulation sequences previously developed in our laboratories played key roles in the syntheses of (±)-13, (±)-14 and (±)-15. A new cyclopentenone annulation procedure was elaborated to assemble the last 5-membered ring of crinipellin B (15). The syntheses of (±)-13 and (±)-14 first involved the conversion of 3-methy1-2-cyclopenten- 1-one (64) into the enone 62 via known chemistry. The enone 62 was transformed into the keto alkene 60 in one step utilizing a methylenecyclopentane annulation method developed previously by Piers and Karunaratne. Thus, conjugate addition of the reagent 18 to the enone 62 afforded the lithium enolate anion 106. This intermediate was allowed to undergo intramolecular alkylation, upon addition of HMPA to the solution containing 106 and warming to room temperature. The keto alkene 60 was converted into the ketone 59 via a sequence of steps which allowed establishment of the correct configuration of the methyl group at C-9. Three synthetic operations on the ketone 59 afforded the enone 120which was successfully transformed into (±)-13 and (±)-14. The synthesis of (±)-crinipellin B (15) was accomplished in 22 steps from the commercially available 2-methyl-2-cyclopenten- 1-one. The starting material was efficiently converted into the bicyclic enone 194 which was subjected to a methylenecyclopentane annulation sequence regioisomeric to that described above. Thus, treatment of 194 with the reagent 209 in the presence of TMSBr provided the vinyl germane 219. A trimethylgermyl-iodine exchange on 219 afforded the vinyl iodide 220, which was allowed to cyclize under conditions ((Ph3)4Pd, t-BuOK, t-BuOH, THF) developed previously by Piers and Marais. The keto alkene 191 was obtained in good overall yield from 194. Three synthetic operations on 191 yielded the ketone 224. A newly elaborated cyclopentenone annulation procedure allowed the conversion of 224 into the enedione 267. Alkylation of 224 with (Z)-3-bromo- 1 -iodopropene (251) gave an intermediate vinyl iodide, which was allowed to undergo cyclization by treatment with n-BuLi in THF. The resultant allylic alcohol 249 underwent oxidative rearrangement to furnish the enedione 267. Two synthetic steps provided the enedione epoxide 188, which was converted into (±)-crinipellin B (15).