钌催化酮的直接不对称还原胺化

手性胺作为一类重要的化合物，在制药、农药及材料科学等领域起重要作用。一直以来高效的手性胺合成方法得到科学家广泛的关注。过渡金属催化的直接不对称还原胺化反应，可以将酮一步转化为手性胺，是现如今化学合成制备手性胺类化合物最为简洁高效的方法之一。近年来，钌催化的铵盐为氨源的不对称还原胺化直接制备手性伯胺受到了广泛关注，并得到了一定程度的发展。然而，该方法仍然存在很大的底物限制，需要进一步研究，发展出更为普适、高效的手性伯胺制备方法。

为实现酮的高效、高选择性不对称还原胺化，用以得到手性伯胺，本文将继续探索醋酸钌-手性双膦配体体系催化的直接不对称还原胺化，希望能够发展出适用范围广高效可靠的用于各种手性伯胺制备的不对称还原胺化方法。本文研究了以α-酮酰胺为底物，氢气作为还原剂，利用醋酸钌-轴手性双膦配体络合物作为催化剂的不对称还原胺化反应。该方法具有良好的底物普适性，实现了α-芳基取代的α-酮酰胺、α-烷基取代的α-酮酰胺的不对称还原胺化反应，高效制备得到N非保护的非天然α-氨基酸衍生物。利用动态动力学拆分，该方法同样实现有两个手性中心的β-芳基-β-烷基取代的α-氨基酸衍生物的不对称还原胺化。除此之外，本文同样完成了以α-三氟苯乙酮为底物，醋酸铵为氨源，一步构建N非保护的手性α-三氟乙胺的方法。本文中完成不同电性取代的α-三氟乙胺底物的高效高选择性合成。最后本课题通过完成反应放大实验以及生物活性分子的合成证明该体系的应用潜力。

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