Application of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane derivatives in asymmetric organocatalysis: the Biginelli reaction
Application of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane derivatives in asymmetric organocatalysis: the Biginelli reaction
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DOI：
10.3998/ark.5550190.0009.606
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发表时间：
2008-01-01
期刊：
影响因子：
0.9
通讯作者：
Juaristi, Eusebio
中科院分区：
文献类型：
--
作者：
Gonzalez-Olvera, Rodrigo;Demare, Patricia;Juaristi, Eusebio
本文介绍了三种手性双环二胺作为有机催化剂在对映选择性Biginelli反应中的应用。该反应的产物是3,4-二氢嘧啶-2(1H)- 1 (DHPM)，这是一种具有重要生物活性的杂环。发现(1S,4S)-2,5-重氮杂环[2.2.1]庚烷中心点2HBr(1)及其n -甲基化衍生物2能有效催化乙酰乙酸乙酯、代表性芳香醛和尿素之间的反应，得到预期的DHPMs，产率高，对映选择性中等，为18-37% ee，有利于(S)对映体（类似对映诱导）。在10mol %的氢溴盐(1S,4S)-2-[(R)-1-苯乙基]-2,5-重氮杂环[2.2.1]庚烷中心点2HBr(3)存在下，所期望的dhpm的产率更高（高达94%），对映体过量略高（高达46% ee）。
This report describes the application of three chiral bicyclic diamines as organocatalysts in the enantioselective Biginelli reaction. The product in this reaction is 3,4-dihydropyrimidin-2(1H)-one (DHPM), a heterocycle of great importance owing to its interesting biological activity. It was found that (1S,4S)-2,5-diazabicyclo[2.2.1] heptane center dot 2HBr (1) and its N-methylated derivative 2 effectively catalyze the reaction between ethyl acetoacetate, representative aromatic aldehydes, and urea to afford the expected DHPMs in good yields and moderate enantioselectivities, 18-37% ee, favoring the (S) enantiomer (like enantioinduction). Better yields (up to 94%) and slightly higher enantiomeric excess (up to 46% ee) of the desired DHPMs were obtained in the presence of 10 mol% of the hydrobromide salt (1S,4S)-2-[(R)-1-phenylethyl]-2,5-diazabicyclo[2.2.1] heptane center dot 2HBr (3).