有機催化連鎖外消旋硝基丙烯醇動力學分割之探討

Abstract

利用小分子有機催化劑，進行連鎖不對稱有機催化反應，短時間且高效率地，建構多重原子的鍵結與立體化學中心，是一種高效率的手性合成策略，避免繁瑣的步驟或是保護基的反應操作；此外，藉助反應活化能的差異，造成不同反應速率，進行動力學分割，分離外消旋化合物，並得到兩種高光學純度的分子，減少廢棄物生成，具有發展潛力。本實驗發展出以-雙苯基脯胺醇三甲基矽醚和酸試劑作為反應共催化劑，促使醛類分子與硝基丙烯醇，進行Michael加成/縮醛化反應，合成出多取代四氫吡喃化合物。透過10 mol%的苯甲酸，作為反應酸試劑，在1, 2-二氯乙烷為反應溶劑的條件，反應溫度為0 oC，並在-雙苯基脯胺醇三甲基矽醚（10 mol%）存在的最佳條件下，進行不對稱連鎖催化反應，可獲得不錯產率，鏡像超越值最高為99% ee的四氫吡喃衍生物，並且回收掌性硝基丙烯醇分子，光學純度最高達97% ee。

Asymmetric organocatalytic domino reactions are highly efficient synthetic strategies by utilizing organocatalyst, these reactions which involving two or more bond-forming reactions and several stereogenic centers efficiently in short term, and avoid operating complicated protection/deprotection steps. Kinetic resolution is one of the potentially developed concepts, which might obtain enantioriched targeted product and separated optical unreactive recovery simultaneously through different activation energy. Here we report an efficient -diphenyl-L-prolinol trimethyl silyl ether and acidic additive-promoted Michael/acetalization reaction of various aldehydes and nitro allylic alcohols, and acquire expected tetrahydorpyrans. The reaction is carried out by taking aldehydes and nitro allylic alcohols, in presence of catalyst（10 mol%）and benzoic acid（10 mol%）in the DCE at 0 oC, which proceeds by way of a catalyzed Michael/acetalization reaction sequence obtaining the products with good yields and excellent stereoselectivities（up to 99% ee）, in regard to the recovered nitro allylic alcohols, all we can receive good-to-excellent enantiomeric excess（up to 97% ee）.