以有機不對稱催化連鎖反應合成多取代四氫吡喃併吡唑分子
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2018
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Abstract
利用小分子掌性有機催化劑，進行不對稱連鎖反應，可在短時間內建構數個新的化學鍵結與立體中心，為環保且高效率之有機合成策略。共軛烯炔是具多官能基之親電試劑，然而過往文獻中，大部分是利用金屬活化或是有機催化劑結合金屬方式，進行合成反應，使用非金屬催化劑的相關報導屈指可數。
本研究利用有機催化不對稱反應，以共軛烯炔、吡唑啉酮與丁烯酮為起始物，二氯甲烷為溶劑，在少量雙官能基催化劑作用下，並添加鹼試劑1,8-二氮雜二環[5.4.0]十一碳-7-烯及丁烯酮，經由不對稱Michael/oxa-Michael/Michael連鎖反應，合成多取代且具有一個四級碳立體化學中心之四氫吡喃併吡唑，產率（84-98 %）、非鏡像選擇性（dr >20 : 1）與鏡像選擇性（82-95 %）皆有優異的表現。期待日後此合成方法在相關學術及產業界應用有所貢獻，而相關合成應用目前仍在本實驗室進行中。
Asymmetric organocatalytic tandem reactions are environmental friendly and highly efficient synthetic strategies by utilizing chiral organocatalyst, which allow for the construction of multiple new chemical bonds and stereogenic centers in short time. Enyne, a highly functionalized reagent, was mostly activated by metal complexes or organocatalysts combined metal reagents to carry out the synthesis reaction according to past literature. However, there is only few reports using non-metal catalysis be published. In this research, an efficient organocatalytic tandem reaction among 1,3-enynes, pyrazolones and methyl vinyl ketone has been designed that furnishes highly functionalized tetrahydropyranopyrazole with a quaternary stereocenter in excellent chemical yields (84-98%) and outstanding stereoselectivities (ee =82-95 % and dr >20 : 1) in the presence of few amount of bifunctional squaramide catalyst and 1,8-diazabicyclo(5.4.0)undec-7-ene through an Michael/oxa-Michael/Michael tandem sequence. Hope that this synthesis method will contribute to the relevant academic and industrial applications in the future, and the related synthetic applications are still in progress in our laboratory.
Asymmetric organocatalytic tandem reactions are environmental friendly and highly efficient synthetic strategies by utilizing chiral organocatalyst, which allow for the construction of multiple new chemical bonds and stereogenic centers in short time. Enyne, a highly functionalized reagent, was mostly activated by metal complexes or organocatalysts combined metal reagents to carry out the synthesis reaction according to past literature. However, there is only few reports using non-metal catalysis be published. In this research, an efficient organocatalytic tandem reaction among 1,3-enynes, pyrazolones and methyl vinyl ketone has been designed that furnishes highly functionalized tetrahydropyranopyrazole with a quaternary stereocenter in excellent chemical yields (84-98%) and outstanding stereoselectivities (ee =82-95 % and dr >20 : 1) in the presence of few amount of bifunctional squaramide catalyst and 1,8-diazabicyclo(5.4.0)undec-7-ene through an Michael/oxa-Michael/Michael tandem sequence. Hope that this synthesis method will contribute to the relevant academic and industrial applications in the future, and the related synthetic applications are still in progress in our laboratory.
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有機催化合成, 連鎖反應, 方醯胺, 共軛烯炔, 四氫吡喃併吡唑, organocatalytic synthesis, tandem reaction, squaramide, 1, 3-enyne, tetrahydropyranopyrazole