本論文利用密度泛函理論計算方法 M06-2X 搭配基底函數 6-31++G(d,p) 並用連續極化模型模擬二甲基亞礬的溶劑效應，來探討以去甲基尼古丁為催化劑進行曼尼希反應的可行性。

我們將該催化反應的計算分為三個主要部份，第一個部份為去甲基尼古丁藉由水分子的幫助和酮類分子形成去甲基尼古丁衍生烯胺。第二個部份為去甲基尼古丁衍生烯胺和亞胺的立體控制步驟之計算，在該部份中去甲基尼古丁衍生烯胺因為水分子的參與而和亞胺形成碳-碳單鍵。第三部份則為利用水分子將在立體控制步驟形成的中間產物進一步反應得到去甲基尼古丁和最終的曼尼希產物。

透過上述的三個部份反應和無催化劑之曼尼希反應的能障計算，我們認為去甲基尼古丁在含水的二甲基亞礬溶劑中對曼尼希反應具有催化的效果，其中可以看出水分子在整體的反應過程中扮演著關鍵性的角色，這提高了去甲基尼古丁催化曼尼希反應在含水有機溶劑或是水溶液中進行的可行性。另外，根據我們對四條可能的立體控制步驟之探討和計算，我們認為該催化反應傾向於得到S型曼尼希產物。

The nornicotine catalyzed Mannich reaction and its mechanism are analyzed with quantum chemical calculations by M06-2X/6-31++G(d,p) method and the polarizable continuum model (PCM) for the solvent effect of dimethyl sulfoxide. The Mannich reaction with nornicotine as a catalyst can be separated into three steps. First, the nornicotine-derived enamine is generated from nornicotine and a ketone with the aid of a water molecule. Second, the nornicotine-derived enamine forms a C-C bond with the imine to produce a chiral intermediate with the assistance of a water molecule. There are four possible stereo-control paths and the analysis suggests that nornicotine as a catalyst favors the S- over R-Mannich product. Third, water catalyzes the release of the original nornicotine catalyst from the Mannich product. The calculation indicates that water is a key element in the proposed mechanism and that nornicotine can catalyze the Mannich reaction in wet solvents or even pure water.

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