Metal-Mediated Routes to Biaryls

描述(申请人提供)：联芳基代表天然和非天然产物化学的一个主要领域。鉴于自然界中广泛存在含有联芳基轴的生理活性化合物，其中许多由于受阻旋转而具有轴向手性元素，因此需要方法学来应对这些特殊的合成挑战。突出现有局限性但为这一领域取得重大进展提供机会的代表性目标包括临床基本抗生素万古霉素和有效抗艾滋病的联芳胺。使用在芳基卤化物偶联伙伴中合理放置的内部膦配体，我们基于铃木-联芳基偶联的关键方法对万古霉素联芳基和胶束胺亚单位的方向性将得到控制。或者，应用于万古霉素的立体控制联芳基的概念上的新进入，将使用取代的非外消旋endiyne的Bergman环化来进行。 联芳基结构的化学通常是在溶液中使用Pd(0)催化进行的，将通过另一种金属体系进行研究：镍。本文提出了基于Ni/C的多相催化的新方法，这些方法将在微波条件下进行考察，而新一代的镍/石墨(“Ni/CG”)似乎提供了不同的反应活性曲线。 最后，将构建一系列新的基于联萘核的非外消旋配体，特别是Nobin。提出的方法将提供进入这一配基系统上前所未有的替代模式，以及它们安装在固体载体上的机会，以便在不同的条件下使用和重复使用。一个特殊的，但具有代表性的，新的取代环-诺宾的应用将被研究选择不对称的Aldol反应。

DESCRIPTION (provided by applicant): Biaryls represent a major area of natural and unnatural products chemistry. Given the widespread occurrence of physiologically active compounds in Nature that contain a biaryl axis, many of which due to hindered rotation possess an element of axial chirality, methodology is needed to respond to these special synthetic challenges. Representative targets which highlight existing limitations yet which provide opportunities for significant advances in this area include the clinically essential antibiotic vancomycin, and the potent anti-AIDS biaryls, the michellamines. Using a judiciously placed internal phosphine ligand in an aryl halide coupling partner, the directionality associated with our key Suzuki-biaryl coupling-based approach to the vancomycin biaryl and the subunits of the michellamines will be controlled. Alternatively, a conceptually new entry to stereocontrolled biaryls, as applied to vancomycin, will be pursued using a Bergman cyclization of a substituted nonracemic endiyne. The chemistry of biaryl constructions, which is usually effected in solution using Pd(0) catalysis, is to be pursued via an alternative metal system: nickel. Proposed herein are new methods for heterogeneous catalysis based on Ni/C, to be examined under microwave conditions, and the next generation species nickel-on-graphite ("Ni/Cg"), which appears to offer a different reactivity profile. Finally, a new series of nonracemic ligands based on the binaphthyl core, in particular of NOBIN, will be constructed. The approach presented will provide entry to unprecedented substitution patterns on this ligand system, as well as opportunities for their mounting on a solid support for use, and re-use, under heterogeneous conditions. A particular, albeit representative, application of a novel substituted cyclo-NOBIN will be studied for selected asymmetric aldol reactions.