多取代環己烷化合物之有機催化連鎖環化反應
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2013
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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.
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