多取代螺環己烷化合物之有機催化[4+2]連鎖環化反應
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2014
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有機合成研究領域，以生成單一碳-碳鍵為主。若要合成官能基複雜天然物，需要數十步驟，官能基保護與去保護反應之間，使得產率銳減、降低原子使用率及造成能源浪費等問題。因此化學家開發不對稱有機連鎖合成策略，合成多個掌性中心的產物分子反應，開展有機合成新的領域，經由建立多個碳-碳鍵以及立體化學中心，合成具高鏡像選擇性的化合物，此合成方法在天然物全合成與藥物設計有更多應用性。本實驗使用2-芳香環亞甲基氫茚-1‚3-二酮和戊二醛，加入20 mol%的‚-L-雙苯環脯胺醇矽醚有機催化劑及20 mol%N,N-二異丙基乙基胺（N,N-diisopropyl ethylamine，DIPEA），在乙醚為溶劑及反應溫度為0 ℃下，進行不對稱催化Michael/aldol連鎖反應。經由簡單的操作，此一鍋化的反應，順利獲得多取代環己烷螺環之產物，其有優異的產率(yield = 99%)及非常良好的立體選擇性(>95:5 dr和95% ee)。藉著核磁共振儀，分析產物中各個氫原子的分裂狀況，並經由單晶繞射X-ray，確認其產物絕對立體組態。期待此合成方法，在產業界及學術界有所貢獻。
The field of organic syntheses that main work is to generate single carbon-carbon bond in the past. To the synthesis complex natural products with multifunctional groups need dozens of steps. Between protection and deprotection in the functional groups, it will cause decreasing yield, reducing atom economy and energy wastage. Chemist developed the strategy of asymmetric organocatalytic to solve the issues. The products with multifunctional groups and chiral centers can be manufactured in one pot reaction. Through carbon-carbon built and chiral center constructed, that is able to synthesize highly enantioselectivity and yield products and apply to nature products total synthesis and drug design. The brand-new organic syntheses concept is worthy of further study. In this experiment, treatment of 2-arylideneindane-1‚3-diones with glutaraldehyde using a catalytic amount of ‚-L-diphenylprolinol trimethylsilyl ether (20 mol%) and DIPEA (20 mol%) in diethyl ether at 0 oC to give multisubstituted spirocyclohexanes via domino Michael-aldol reaction. This one-pot sequential catalysis for construction of substituted spirocyclohexane carbaldehydes with three stereocenters via a formal [4 + 2] annulation strategy is synthetically useful. Simple operated, we obtain good chemical yields and high-to-excellent stereoselectivities (>95:5 dr and 95% ee). The split and interaction of hydrogen atoms are analyzed by NMR. The absolute conformation is confirmed by X-ray ORTEP spectra.
The field of organic syntheses that main work is to generate single carbon-carbon bond in the past. To the synthesis complex natural products with multifunctional groups need dozens of steps. Between protection and deprotection in the functional groups, it will cause decreasing yield, reducing atom economy and energy wastage. Chemist developed the strategy of asymmetric organocatalytic to solve the issues. The products with multifunctional groups and chiral centers can be manufactured in one pot reaction. Through carbon-carbon built and chiral center constructed, that is able to synthesize highly enantioselectivity and yield products and apply to nature products total synthesis and drug design. The brand-new organic syntheses concept is worthy of further study. In this experiment, treatment of 2-arylideneindane-1‚3-diones with glutaraldehyde using a catalytic amount of ‚-L-diphenylprolinol trimethylsilyl ether (20 mol%) and DIPEA (20 mol%) in diethyl ether at 0 oC to give multisubstituted spirocyclohexanes via domino Michael-aldol reaction. This one-pot sequential catalysis for construction of substituted spirocyclohexane carbaldehydes with three stereocenters via a formal [4 + 2] annulation strategy is synthetically useful. Simple operated, we obtain good chemical yields and high-to-excellent stereoselectivities (>95:5 dr and 95% ee). The split and interaction of hydrogen atoms are analyzed by NMR. The absolute conformation is confirmed by X-ray ORTEP spectra.
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一鍋化, 多取代螺環己烷, 不對稱有機催化連鎖反應, One pot, Substituted spirocyclohexanes, Organocatalytic synthesis