Convergent Synthesis via Asymmetric Catalysis

描述(申请人提供)：该项目的重点是镍催化的碳-碳键形成反应的开发和应用，用于合成具有医学意义的重要有机分子。我们开发的方法将用于合成几种两性内酯天然产物，西波尔丁A和二恶烷脱氢百里香醇。这些化合物以前都不是通过全合成制备的。将开发两类新的镍催化反应。两者都涉及未活化的α-烯烃的偶联，每年以公吨数量制备。正在开发的一类新的偶联反应涉及具有累积双键的亲电体，如二氧化碳、烯类和碳二亚胺。这三种化合物中的每一种都将容易获得的原料联合起来，分别用于合成具有合成价值的化合物、丙烯酸、烯酮和酰胺。另一类反应都涉及共轭加成反应，在这种情况下的进展是，α-烯烃是一种没有任何明显活化基团的烯烃，起着亲核剂的作用。 本项目的重点是开发和应用镍催化的碳-碳键形成反应来合成医学上重要的有机分子，包括两面体内酯、西伯来定A和二恶英脱氢百里香醇。在该项目的另一部分中，将开发两类新的镍催化反应，每一类反应都将现成的原料联合起来，制造出具有合成价值的化合物。

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.