新穎的三組分反應之開發與其結合一鍋化方式製備多官能基的烯類化合物

陳佩怡

指導教授 ： 林文偉

國立臺灣師範大學/理學院/化學系/碩士(2010年)

摘要

多組分反應在有機化學中扮演著重要的角色，它可結合三個或多個反應物，利用單一操作就可得到複合產物，是符合經濟效應與環保的合成方法。Baylis-Hillman反應為有效生成碳-碳鍵的方法之一，其產物為好的Michael acceptor，藉由親核試劑的加成可成功的應用於合成許多高官能基化合物。然而，Baylis-Hillman反應速度緩慢而最後得到Michael加成的產物通常需要花費數天的反應時間。
本篇論文主要是以醛類、烷基丙烯酸酯和醯胺化合物在EtPPh2催化下進行tandem三組分反應合成出多官能基的產物。反應機構主要為醛類與烷基丙烯酸酯先進行Baylis-Hillman反應，接著醯胺化合物再Michael加成到Baylis-Hillman產物上即可得到三組分產物，產率為66-88%。除此之外，也開發出利用醛類、烷基乙烯基酮及不同親核試劑，在PPh3催化下進行tandem三組分反應，其產物可應用在一鍋化條件下合成出多官能基烯類化合物，反應時間為3-29.5小時，產率為80-98%，立體選擇性可高達E/Z = 97/3。

關鍵字

Morita-Baylis-Hillman反應 ； 三組分反應 ； Tandem 反應

並列摘要

The multi-component reaction plays an important role in organic chemistry. It allows generation of an adduct in a single operation from three or more reactants. Therefore, it has economic benefits and becomes one of useful “green” synthetic methods. The Baylis-Hillman reaction is a well-known method to create carbon- carbon bond. Numerous successful applications for syntheses of highly functional compounds were achieved by the Michael addition of nucleophiles toward the Baylis-Hillman adducts, which are good Michael acceptors, as routine protocols. However, the Baylis-Hillman reaction is very slow, and therefore the whole process often takes several days to obtain the final Michael product.
We have successfully developed EtPPh2-catalyzed tandem three-component reaction of aldehyde, alkyl acrylate, and amide to afford the highly functional products (66-88% yields). The reaction mechanism is proposed to undergo the Morita-Baylis-Hillman reaction of aldehyde and alkyl acrylate followed by Michael addition of amide toward the corresponding adduct. Besides, a general procedure for one-pot syntheses of highly functional α,β-unsaturated ketones via tandem PPh3-catalyzed three-component reaction of aldehydes, alkyl vinylketones and amides is also developed. A wide variety of highly functional α,β-unsaturated ketones can be furnished in 80-98% yields with high stereoselectivity (E/Z up to 97: 3) within overall 3-29.5h.

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