Studies on Palladium-Catalyzed reactions and their synthetic application to biologically active compounds

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Synthetic studies on glycinoeclepin A has been examined according to the following reaction sequences. l-Menthone was treated with m-CPBA in dichloromethane at room temperature to give the 7-membered lactone in 94% yield. Methylation of the lactone thus obtained proceeded very smoothly at -10 ﾟC by the reaction of the enolate generated with lithium bis (trimethylsilyl) amide in THF at -10 ﾟC with iodomethane. Then highly stereoselective allylation was realized by treating the enolate generated with potassium bis (trimethylsilyl) amide at -30 ﾟC with 2-bromopropene, providing dialkylated 7-membered lactone. The relative configuration of the vicinal dimethyl groups was confirmed to be cis by NOE experiments.The ring opening of the lactone was effected very smoothly to give the dimethylamide by refluxing in toluene with excess aluminum amide reagent prepared from the trimethylaluminum and dimethylamine hydrochloride. Oxidative cleavage of the terminal double bond with OsO_4/NaIO_4 and the subsequent acetalizatio with ethylene glycol provided the acetal in 61% overall yield. Oxidation of the alcohol with TPAP to the ketone and the subsequent silyl enol ether formation proceeded in 79% overall yield. Then, oxidation of the silyl enol ether with m-CPBA and the suspequent deprotection with TBAF gave rise to the alpha-keto alcohol which, without purification, was cleaved with NaIO_4 to give the aldehyde. Reduction of the aldehyde with NaBH4 and protection with MPMCl provided the amide acetal in 60% overall yield.