Convergent Synthesis via Asymmetric Catalysis

描述（由申请人提供）：该项目的重点是开发和应用镍催化的碳-碳键形成反应，用于合成具有医学重要性的有机分子。我们已经开发的方法将被用于合成几个amphidiniferous天然产物，sieboldine A，和dioxepandehydrothyrsiferol。这些化合物以前都没有通过全合成制备。将开发两种新的镍催化反应。两者都涉及未活化的α烯烃的偶联，其每年以公吨量制备。正在开发的一类新的偶联反应涉及具有累积双键的亲电试剂，如二氧化碳、烯酮和N-酰亚胺。每一种都结合了容易获得的起始材料，分别制备有合成价值的化合物，丙烯酸，烯酮和脒。另一类中的反应都涉及共轭加成反应，在这种情况下的进步是α烯烃，一种没有任何明显活化基团的烯烃，起亲核试剂的作用。 该项目的重点是开发和应用镍催化的碳-碳键形成反应，用于合成具有重要药用价值的有机分子，包括两性环内酯，sieboldine A和二氧杂环庚烷脱氢thyrsiferol。在该项目的另一部分中，将开发两种新的镍催化反应，每种反应都结合了现成的起始材料，以合成有价值的化合物。

DESCRIPTION (provided by applicant): The focus of this project is the development and application of nickel-catalyzed carbon-carbon bond-forming reactions for the synthesis of medicinally important organic molecules. Methods that we have developed will be utilized in the synthesis of several amphidinolide natural products, sieboldine A, and dioxepandehydrothyrsiferol. None of these has previously been prepared by total synthesis. Two new classes of nickel-catalyzed reactions will be developed. Both involve the coupling of unactivated alpha olefins, which are prepared in metric ton amounts annually. One new class of coupling reaction under development involves electrophiles with cumulated double bonds such as carbon dioxide, ketenes, and carbodiimides. Each of these unites readily available starting materials to make synthetically valuable compounds, acrylic acids, enones, and amidines, respectively. The reactions in the other class all involve conjugate addition reactions, with the advance in this case being that the alpha olefin, an alkene without any obvious activating group, functions as the nucleophile. The focus of this project is the development and application of nickel-catalyzed carbon- carbon bond-forming reactions for the synthesis of medicinally important organic molecules, including amphidinolides, sieboldine A, and dioxepandehydrothyrsiferol. In another part of this project, two new classes of nickel-catalyzed reactions will be developed, and each of these unites readily available starting materials to make synthetically valuable compounds.