手性螺环双吲哚骨架的催化不对称构建及其应用研究

1,1’-螺二氢茚的类似物(类SPINOL)广泛应用于催化不对称与材料等领域。随着该类骨架的合成以及应用不断被报道，人们发现在这类螺环骨架中引入杂原子会改变其二面角以及螯合基团的空间位置，从而影响其衍生物的催化活性。

然而，目前含杂原子的螺环骨架类型较少，需要复杂的合成路线与繁琐的手性拆分步骤。同时，杂原子存在于螺环上，难以引入并且稳定性有限。通过杂芳环在螺环中引入杂原子的构建方法与应用研究有限，杂芳环碳螺环骨架的性质尚未开发。吲哚是自然界丰富的杂原子芳烃，在催化不对称领域应用广泛，因此利用不对称催化的方式构建光学纯的螺环吲哚化合物具有一定的科学价值。

近年来，双吲哚化合物因其优异的生物活性，在生物以及材料领域取得卓著的成果，手性螺环双吲哚化合物的开发有着丰富的应用前景。本文筛选不同的醛基吲哚，以4-醛基吲哚作为起始原料，经过两步合成双螺环吲哚的环化前体。通过对催化剂的筛选与改造，探究了影响底物反应速率以及实现优异对映选择性控制的关键因素。最终在手性磷酸(CPA)的催化下，首次构建了轴手性螺环吲哚4,4’,5,5’-四氢螺苯并吲哚骨架(SBENDOLE)，并且进行了对称与非对称类型的底物进行了拓展。包括烷基、芳基以及杂环取代基，以中等偏上的收率及优异的对映选择性得到对应的螺环双吲哚化合物，验证了该方法的底物普适性 (14 examples, up to 97% yield, 99% ee)。

本文后半部分初步研究了SBENDOLE的应用价值，通过溴取代以及硫取代的反应验证了SBENDOLE具有与吲哚类似的化学性质。并由该骨架衍生出不同种类的手性催化剂以及配体，例如手性硫脲，手性膦氧化合物等。值得注意地是，在该类螺环骨架的基础上合成了多环芳烃的手性荧光分子，具有良好的CPL性质以及量子荧光效率。这些证明了SBENDOLE骨架在材料以及催化领域有潜在的应用前景，此外SBENDOLE骨架作为轴手性螺环双吲哚甲烷分子，本身在生物医药，尤其是抗癌药物的研发领域具有巨大的价值。上述因素使SBENDOLE具备成为手性双吲哚“平台分子”的潜力。

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