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

钯催化反应及其在生物活性化合物合成中的应用研究

• 批准号: 05453132
• 负责人: TSUJI Jiro
• 金额: $ 4.54万
• 依托单位: Okayama University of Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05453132/
• 关键词: Palladium cafalyst; Carbonylation; Glycinoeclepin A; l-Menthone; Propargyl carbonate; Carbon monoxide; グリシノエクレピンA; 炭酸プロパルギルエステル; ビシナルジカルボニル化; トリエステル; エン反応; ギ酸プロパルギルエステル; 加水素分解反応; 2置換アセチレン; 共役エンイン

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.

大豆凝集素A的合成研究按以下反应顺序进行。L-薄荷酮在二氯甲烷中与间CPBA反应制得7元内酯，产率为94%。在-10ﾟC下，双(三甲基硅基)胺锂在四氢呋喃中生成的烯酸酯与碘甲烷反应，得到的内酯在-10ﾟC下的甲基化反应非常顺利。在-30ﾟC下，双(三甲基硅基)酰胺钾与2-溴丙烯反应生成的烯醇酸酯与2-溴丙烯反应得到二烷基7元内酯，从而实现了高立体选择性的烯丙化反应。NOE实验证实了邻二甲基团的相对构型为顺式，内酯在甲苯中与过量的盐酸二甲胺铝试剂回流，使内酯开环非常顺利，得到了二甲胺。用OSO4/NaIO4氧化裂解末端双键，然后与乙二醇缩醛，总收率为61%。用TPAP将醇氧化成酮，然后生成硅烯醇醚，总收率为79%。然后用m-CPBA氧化硅烯醇醚，用TBAF去保护，得到α-酮醇，不经提纯，用NaIO_4裂解得醛。用NaBH4还原缩醛，用MPMCl保护，总收率为60%。

项目成果

T.Mandai, J.Tsuji: "A new candidute for a properly substituted" J.Org.Chem.59. 5847-5849 (1994)

T.Mandai、J.Tsuji：“适当替代的新候选者”J.Org.Chem.59。

T.Mandai, J.Tsuji: "Preparation of alpha-Vinylidene-alpha-lactones-" J.Organometal.chun.488. 127-131 (1995)

T.Mandai、J.Tsuji：“α-亚乙烯基-α-内酯的制备”J.Organometal.chun.488。

T.Mandai, J.Tsuji: "Tandem pulludiun-Catalyzed curbonylation and intramolecular ene reaction-" Tetruhedron Lett.35. 5701-5704 (1994)

T.Mandai，J.Tsuji：“串联普鲁迪恩-催化的限制性化和分子内烯反应-”四面体快报.35。

T.Mandai,J.Tsuji,Y.Tsujiguchi,S.Saito: "a novel route to cross-conjugated 4-oxo-5-alkylidene-2-cyclopenten carboxylates by Pd(O)-catalyzed vicinal carbonylation of 4-en-2-ynyl carbonates" J.Am.Chem.Soc.,. 115. 5865-5866 (1993)

T.Mandai，J.Tsuji，Y.Tsujiguchi，S.Saito：“通过 Pd(O) 催化 4-en- 的邻位羰基化来交叉共轭 4-oxo-5-alkidene-2-cyclopenten 羧酸盐的新途径

T. Mandai, J. Tsuji: "Tanden Palladium Catulyzed cuibonylation and in trumolecular ene reaction of 1-(2-jnesliylcahonyl etlty)-4-alkenyl methyl caibonde" Tetirhedvion letters. 35. 5701-5704 (1994)

T. Mandai、J. Tsuji：“Tanden Palladium Catulyzed cubonylation and in trumolecular ene reaction of 1-(2-jnesliylcahonyl etlty)-4-alkenylmethyl caibonde”Tetirhedvion 字母。