CATALYTIC ENANTIOSELECIVE SYNTHESIS OF ALLYLAMINES

虽然利用手性刘易斯酸在不对称C-C键形成方面取得了很大进展，但很少关注高选择性的C-N键的构建。本研究提出了一种通过[3，3] σ转移重排反应合成烯丙基胺的催化对映选择性方法。本研究旨在拓展双恶唑啉-金属刘易斯酸配合物催化的对映体选择性反应的范围。 埃文斯从这些刘易斯酸的结构和机理研究中获得的关于这些体系的知识为检验这一假设提供了基础。该提案首先提出酰基异氰酸酯作为双齿底物，这将允许利用有组织的阳离子双（恶唑啉）-铜-底物络合物进行不对称诱导。将取代的烯丙基醚或硫醚加成到刘易斯酸活化的酰基异氰酸酯中产生与手性配体-金属络合物结合的反应性中间体。随后的[3，3]重排在手性环境中进行，从而提供作为酰基氨基甲酸酯的双保护的手性烯丙胺。与使用具有相同绝对构型的三齿吡啶基-双（恶唑啉）配体相比，使用二齿双（恶唑啉）配体提供了在新形成的中心处具有相反立体化学的手性烯丙基胺。本文所述实验的成功实现将评估该双（恶唑啉）-金属络合物催化不对称σ迁移重排的能力。从这些实验中获得的信息将被用来开发新的催化对映选择性反应。

While great advances have been made in asymmetric C-C bond formation utilizing chiral Lewis acids, less attention has been focused on the construction of C-N bonds with high levels of selectivity. This research proposal describes the development of a catalytic enantioselective method to synthesize allylamines via a [3,3] sigmatropic rearrangement. This study aims to extend the scope of enantioselective reactions catalyzed by bis(oxazoline)- metal Lewis acid complexes. The knowledge about these systems from structural and mechanistic studies of these Lewis acids by Evans provides a foundation on which to test this hypothesis. The proposal first presents acyl isocyanates as bidentate substrates that will allow the utilization of organized cationic bis(oxazoline)-copper-substrate complexes for asymmetric induction. Addition of substituted allylic ethers or thioethers to the Lewis acid activated acyl isocyanate generates a reactive intermediate bound to the chiral ligand-metal complex. The subsequent [3,3] rearrangement proceeds in a chiral environment, thus providing a chiral allylamine doubly protected as an acylcarbamate. Use of the bidentate bis(oxazoline) ligand provides chiral allylamines with the opposite stereochemistry at the newly formed center compared to the use of the tridentate pyridyl-bis(oxazoline) ligands of the same absolute configuration. The successful realization of the experiments described within will evaluate the ability of this bis(oxazoline)-metal complexes to catalyze asymmetric sigmatropic rearrangements. Information gained from these experiments will be utilized to develop new catalytic enantioselective reactions.