Convergent Synthesis via Asymmetric Catalysis

项目描述（申请人提供）：本项目的重点是镍催化碳-碳成键反应的开发和应用，用于合成具有重要药用价值的有机分子。我们开发的方法将用于合成几种两苯二酚内酯天然产物、希泊尔定A和二氧乙基脱氢thyrsiferol。这些物质以前都没有用全合成法制备过。将开发两类新的镍催化反应。两者都涉及未活化α -烯烃的偶联，每年以公吨的数量制备。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、烯酮和碳二亚胺。它们中的每一种都结合了现成的起始材料，分别合成有合成价值的化合物，丙烯酸、烯酮和脒。另一类反应都涉及共轭加成反应，在这种情况下的进步是-烯烃，一种没有明显活化基团的烯烃，起亲核试剂的作用。

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.