Metal-Mediated Routes to Biaryls

描述（由申请人提供）：联芳基化合物代表了天然和非天然产物化学的主要领域。考虑到自然界中含有联芳基轴的生理活性化合物的广泛存在，其中许多化合物由于受阻旋转而具有轴向手性元素，因此需要方法来应对这些特殊的合成挑战。突出现有限制但为该领域的重大进展提供机会的代表性靶标包括临床必需抗生素万古霉素和有效的抗AIDS联芳基化合物，即米歇尔胺。使用明智地放置在芳基卤化物偶联配偶体中的内部膦配体，将控制与我们的关键Suzuki-联芳基偶联方法相关的万古霉素联芳基和米歇尔胺亚基的方向性。或者，一个概念上的新进入立体控制的联芳基，如应用于万古霉素，将追求使用Bergman环化取代的非外消旋烯二炔。 联芳基结构的化学，通常在溶液中使用Pd（0）催化剂进行，将通过替代金属系统进行：镍。本文提出了用于基于Ni/C的非均相催化的新方法，其在微波条件下进行检查，以及下一代物种石墨上镍（“Ni/Cg”），其似乎提供不同的反应性特征。 最后，一系列新的非外消旋配体的基础上的联萘核心，特别是NOBIN，将被构建。所提出的方法将提供进入前所未有的取代模式，这种配体系统，以及安装在固体支持使用的机会，和重复使用，在异质条件下。一个特定的，虽然代表性的，一种新的取代环NOBIN的应用将被研究选定的不对称羟醛缩合反应。

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.