經由不對稱有機連鎖1,6/1,4-加成反應合成雙環[3.3.1]壬-9-酮架構

Abstract

利用有機小分子進行連鎖催化反應，為有效率之有機合成策略，另一方面，不對稱有機催化1,6-加成反應則較具挑戰。使用二烯化合物搭配環己酮的去對稱化反應，進行不對稱有機連鎖1,6-加成反應，可得到良好產率及優異立體選擇性的產物。 本文利用4-甲基環己酮114a為手性前驅起始物，在L-脯胺酸所衍生之有機催化劑I的作用下，與1,3-茚二酮所衍生的二烯化合物104，於室溫下進行1,6加成/1,4加成連鎖反應。得到以雙環[3.3.1]壬-9-酮為主體架構之產物115，產率45% - 99%，非鏡像選擇性> 20:1，鏡像選擇性最高達97% ee。

Organocascade reaction that catalyzed by organic small molecules is an efficient strategy for organic synthesis, on the other hand, asymmetric organocatalytic 1,6-addition cascade reactions are still a challenge. In this study, the addition of prochiral 4-methyl cyclohexanone to diene-tethered indan-1,3-dione proceeded in asymmetric 1,6/1,4-addition manner to give the bicyclo[3.3.1]nonan-9-one products in good yields and with excellent stereoselectivity. The bridged bicyclic products 115 were obtained in 45-99% yields and with excellent stereoselectivities (up to > 20:1 dr and up to 97% ee).