Herrbach Audrey, Marinetti Angela, Baudoin Olivier, Guénard Daniel, Guéritte Françoise
Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
J Org Chem. 2003 Jun 13;68(12):4897-905. doi: 10.1021/jo034298y.
A catalytic asymmetric synthesis of the axially chiral bridged biaryl (-)-2, a structural analogue of natural (-)-rhazinilam possessing original antimitotic properties, is described. The key step is an intermolecular asymmetric Suzuki coupling, furnishing the nonbridged biaryl (-)-6, precursor of (-)-2, with up to 40% ee using binaphthyl ligand 7a. Various known or new binaphthyl and ferrocenyl phosphines as well as phosphetanes were screened as ligands in this reaction, the conditions of which were optimized. The comparison with another Suzuki coupling system showed that 7a is the most versatile ligand described to date for this type of transformation. This work gives the first application of the asymmetric Suzuki coupling to a biologically relevant target.
本文描述了轴向手性桥连联芳基化合物（-）-2的催化不对称合成，（-）-2是天然（-）-rhazinilam的结构类似物，具有独特的抗有丝分裂特性。关键步骤是分子间不对称铃木偶联反应，使用联萘配体7a，以高达40%的对映体过量（ee）得到非桥连联芳基化合物（-）-6，即（-）-2的前体。筛选了各种已知或新型的联萘基和二茂铁基膦以及磷杂环丁烷作为该反应的配体，并对反应条件进行了优化。与另一种铃木偶联体系的比较表明，7a是迄今为止报道的用于此类转化的最通用配体。这项工作首次将不对称铃木偶联反应应用于与生物学相关的目标。
