鈀金屬錯合物催化芳香基碘化物和炔類的異種偶合、氫芳香基化和擴環加成反應

Palladium-catalyzed Cross Coupling, Hydroarylation and Ring-expansion Reactions of Aryl Iodides with Alkynes

魏麗梅(Li-Mei Wei)

指導教授 ： 吳明忠

高雄醫學大學/藥學院/藥學研究所/博士(2002年)

摘要

近數十年來，利用鈀金屬錯合物為催化劑，生成碳-碳鍵的有機反應，已被有機化學家廣泛地研究。本篇論文主要是探討鈀金屬錯合物催化炔類化合物和芳香基碘化物的異種偶合、氫芳香基化和擴環加成反應。第一部份是以Pd(PPh3)4為催化劑，在甲醇和甲醇鈉的存在下，加熱迴流24小時，可以成功地將2-炔基苯甲氰(2-alkynylbenzonitriles)和芳香基碘化物(aryl iodides)進行連續性環化偶合反應，得到3,4-二取代異奎啉(3,4-disubstituted isoquinolines)和3-二芳香基亞甲基異吲哚(3-diarylmethylideneisoindoles)，在相同的條件下，2-乙炔基苯甲氰(2-ethynylbenzonitriles)和2.5倍當量碘苯，加熱迴流48小時，可得到環化偶合的產物3-二苯基亞甲基異吲哚 (3-diphenylmethyleneisoindole)和少量單偶合的產物3-苯基亞甲基異吲哚(3-phenylmethyleneisoindole)，產率分別為45% 和6%。
第二部份是利用內部乙炔(internal alkynes)和芳香基碘化物，以甲醇為溶劑，在醋酸鈀(Pd(OAc)2)和甲醇鈉的存在下，於室溫下，進行氫芳香基化反應(hydroarylation)，得到三取代乙烯。在此加成反應中，有機鈀金屬的氫分解反應(hydrogenolysis)是經由甲氧根鈀金屬中間物(palladium methanolate)的β-氫脫去反應 (β-hydrogen elimination) 而得到。
第三部份是有關合成2-二芳香基亞甲基環戊酮(2-diarylmethylenecyclopentanones)類似物的新方法，其反應物為1-(1-炔基)環丁醇(1-(1-alkynyl)cyclobutanols)和芳香基碘化物，在醋酸鈀的催化下，以乙氰為溶劑，反應溫度為80 ℃，反應時間為24小時，可以進行連續性擴環加成反應，得到一系列2-二芳香基亞甲基環戊酮。若將鈀金屬催化劑改為Pd(dba)2、Pd(OCOCF3)2和Pd(CH3CN)2Cl2也可得到環戊酮的產物，產率分別為50%、40% 和48%。
於所有使用的鹼中，以有機鹼三乙基胺可得到最高的產率，但改用無機鹼，如碳酸鉀、碳酸鈉和醋酸鈉也可得不錯的產率。

關鍵字

鈀金屬錯合物 ； 芳香基碘化物 ； 炔類 ； 異種偶合 ； 氫芳香基化 ； 擴環加成

並列摘要

The chemistry of palladium has been developed in recent years as a powerful method to promote the formation of carbon-carbon bond. In this thesis, we describe the palladium-catalyzed cross-coupling, hydroarylation and ring expansion-addition reactions of aryl iodides with alkynes.
Firstly, the reaction of aryl iodides with 2-alkynylbenzonitriles in the presence of Pd(PPh3)4 and NaOCH3 in methanol provided 3-diarylmethylideneisoindoles and 3,4-disubstituted isoquinolines via the cross-coupling and cyclization reaction. Reaction of 2-ethynylbenzonitrile with 2.5 equiv. of iodobenzene gave 3-diphenylmethylideneisoindole in 45% yield along with the minor monocoupled adduct 3-phenylmethylideneisoindole in 6% yield.
Secondly, treatment of aryl iodides with disubstituted alkynes in the presence of Pd(OAc)2 and sodium methoxide in methanol afforded trisubstituted ethylenes. The hydrogenolysis of the organopalladium is proposed through β-hydride elimination of the palladium methanolate intermediate.
Finally, the one-step synthesis of 2-diarylmethylidenecyclopentanone derivatives was achieved by the palladium-catalyzed tandem rearrangement and addition of 1-ethynylcyclobutanols with aryl iodides. When the catalyst (Pd(OAc))2 was replaced by Pd(dba)2, Pd(OCOCF3)2 or Pd(CH3CN)2Cl2 under the same reaction conditions, 2-diarylmethylidenecyclopentanones were obtained in modest yields. Triethyl amine (Et3N) was the best base, and other bases, such as K2CO3、Na2CO3 and NaOAc, were less effective.

並列關鍵字

Palladium Complex ； Aryl Iodides ； Alkynes ； Cross Coupling ； Hydroarylation ； Ring-expansion Reactions

參考文獻

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