多取代環己烷化合物之有機催化連鎖環化反應 Organocatalytic Synthesis of Functionalized Cyclohexanes via Domino Michael/Michael/Cyclization Reaction

Date
2013
Authors
簡崇瀚
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Abstract
藉由二分子一鍋化反應,進行不對稱有機催化連鎖反應,發展鏡像選擇性全取代二螺環己烷。本實驗使用2-芳香環亞甲基氫茚-1‚3-二酮和醛類,加入5 mol%的‚-L-雙苯環脯胺醇矽醚有機催化劑及 20 mol%的1‚4-二氮雜二環[2.2.2]辛烷,在二甲基二醯胺為溶劑及-20 oC下,進行Michael/Michael/aldol連鎖反應,得到全取代二螺環己烷,其有不錯的產率及非常好的立體選擇性(>95:5 dr 和 高達 99% ee);除此之外,經由單晶繞射X-ray確認其產物絕對立體組態;另一方面,本實驗也嘗試使用2-(4-硝基苯亞甲基)-氫茚-1‚3-二酮及丙烯醛,以20 mol%的掌性三級胺進行催化,在二甲基二醯胺為溶劑及0 oC下,經由Michael/Michael/cyclization連鎖反應,可得到五取代二螺環己烷,其產率及鏡像選擇性在持續探討中。本實驗成功利用二種不同策略,進行合成多取代環己烷,並且建構兩個四級碳中心,在未來合成發展上極具經濟效益。
An interesting asymmetric organocatalytic domino reaction by using two components have been developed that gives fully substituted dispirocyclohexanes in one pot. In this study‚ treatment of 2-arylideneindane-1‚3-diones with aldehydes using a catalytic amount of ‚-L-diphenylprolinol silyl ether (5 mol%) and DABCO (20 mol%) in DMF at -20 oC to give fully substituted dispirocyclohexanes via domino Michael/Michael/aldol process with moderate chemical yields and high-to-excellent stereoselectivities (>95:5 dr and up to 99% ee). Besides‚ the absolute stereochemistry is determined by single crystal X-ray analysis of product. On the other hand‚ in another study‚ reaction was carried out under 0 oC by using the (2-(4-nitro-benzylidene)-indan-1‚3-dione) and acrolein as starting materials in DMF in the presense of chiral tertiary amine catalyst (20 mol%) to give pentasubstituted dispirocyclohexanes via cascade Michael/Michael/cyclization process but the chemical yields and enantioselectivity has not been optimized. Successfully synthesis of multisubstituted cyclohexanes and construct two all-carbon quaternary by using two diferrent strategy are more commercial for another synthetic development in the future.
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一鍋化, 不對稱有機催化連鎖反應, 多取代二螺環己烷, domino/cascade, dispirocyclohexanes, Michael/Michael/cyclization
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