鈀催化之α芳基化在乙烯類似物上的研究與芳香羅漢松烷二萜類的全合成研究

Palladium-Catalyzed α Arylation Reaction of Cyclic Vinylogous Esters: Total Syntheses of Aromatic Podocarpane-type Diterpenoids

侯文易(Wen-Yi Hou)

指導教授 ： 吳彥谷

國立交通大學/理學院/應用化學系所/碩士(2017年)

摘要

本論文內容共分兩個部分：第一部分為鈀催化之α-芳基化在乙烯類似物上方法學的研究；第二部分則為鈀催化之α-芳基化在天然物上的應用。

第一部分：利用市售的1,3-環己二酮(81)進行三次在不同位置上的烷基化，得到乙烯類似物86，其先與2-甲基-4-溴苯甲醚(88)以溶劑為甲苯，鈀金屬來源為雙(二亞苄基丙酮)鈀，三叔丁基膦為配位體，與多種不同的鋰鹽類鹼進行測試，結果為二環己基氨基鋰得到最好的產率。以上述的條件，乙烯類似物86分別與20種不同的溴化芳香基進行測試，結果為含有推電子官能基與拉電子官能基的溴化芳香基皆可以得到良好的產率(74%～88%)，相對應的產物為化合物100～106；鄰位溴化芳香基可以得到68%的產率，所對應的產物為化合物107；雜環溴化芳香基則可以得到一定的產率，所對應的產物為化合物108～112。

第二部分：我們利用第一部分方法學得到的芳基酯類化合物104與乙烯基溴化鎂進行親核反應，加入酸水溶液之後進行Stork-Danheiser位移，成功地得到共軛二烯酮化合物145，利用路易士酸進行分子內的Friedel–Crafts reaction可得到含有三環骨架的烯酮化合物146，藉由Birch還原條件下進行還原甲基化反應，得到十氫萘系統之三環化合物(±)-142，利用三溴化硼移除化合物142苯環上甲氧基的甲基，成功地得到天然物(±)12-hydroxy-13- methylpo- docarpa-8, 11,13-trien-3-one (133)，對天然物133的酮基進行還原，可得到天然物3β,12-dihydroxy- 13-methyl-podocarpane-8,11,13- triene(134)。
化合物(±)-142與氯鉻酸吡啶鹽進行芐位氧化反應可得到天然物nimbinone 的衍生物 (±)-O-methyl nimbinone (135)

關鍵字

天然物合成 ； 鈀催化 ； α芳基化 ； 二萜類 ； 全合成

並列摘要

The first part of this thesis describes palladium-catalyzed α-arylation reaction of cyclic vinylogous esters. The commercial 1,3-cyclohexedione (81) was undergo three times alkylation on the different atoms of compound 81 to get the vinylogous esters 86. We examined several reaction parameters and found the optimal condition called for the combination of Pd(dba)2 and tBuP3 and lithium dicyclohexylamide acting as a base. The optimized conditions were utilized to conduct the coupling reaction between a vinylogous ester and bromoarenes. Electron-deficient and Electron-rich bromoarenes were effective coupling partners, the corresponding products are compound 100～106. It is noteworthy that the arylation is compatible with a sterically demanding ortho-substituted substrate, albeit at a slower rate (compound 107). We examined the compatibility of heterocyclic bromides in this transformation and it can be applied with good yield and the corresponding products are compound 108～112.
The second part is describle total syntheses of aromatic podocarpane-type diterpenoids. A conjugated dienone 145 was prepared from the arylated product 104 via a Stork−Danheiser transposition that comprises sequential 1,2-addition of vinylmagnesium bromide and acidic hydrolysis. Lewis acid-promoted intramolecular Friedel−Crafts reaction of the dienone 145 led to the formation of a tricyclic compound 146. Reductive alkylation of the tricyclic compound under birch conditions provided the desired trans-decalin system bearing the gem-dimethyl moiety 142. Then, the facile removal of the O-methyl group with boron tribromide delivered racemic 12-hydroxy-13-methylpodocarpa-8,11,13- trien-3-one (133). Following reduction in excellent diastereoselectivity, thus accomplishing the first total synthesis of racemic 3β,12-dihydroxy-13-methyl -podocarpane-8,11,13-triene (134). Finally, we showed that (±)-O-methyl nimbinone (135)could be prepared via benzylic oxidation of compound (±)-142.

並列關鍵字

total synthesis ； Palladium-Catalyzed ； α Arylation ； Diterpenoids

參考文獻

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