Synthetic Study of Biologically Active Chiral Biaryls for Drug

轴向手性双芳烯不仅在不对称反应中作为手性配体或助剂，而且在具有生物活性的天然产物中具有重要意义。为了不对称合成轴手性双芳基，我们研究了平面手性芳基卤化铬三羰基配合物与芳基硼酸的交叉偶联。因此，钯(0)介导的平面手性（2,6 -二取代溴苯）铬配合物与o取代芳基硼酸交叉偶联得到立体选择性轴向手性单Cr(CO)3络合双芳基。交叉偶联产物的轴向立体化学在很大程度上取决于芳基硼酸邻位取代基的空间体积和反应条件。该工艺为从单平面手性（芳烃）铬络合物开始立体选择性制备这两种对映异构体提供了一种很有前途的方法。利用这些方法，立体选择性地合成了具有生物活性的轴向手性天然产物万古霉素甾酮、korupen胺和轴向手性A-B环体系。

Axially chiral biaryls are significantly important not only as chiral ligands or auxiliaries in asymmetric reactions but also for biologically active natural products. For the asymmetric synthesis of axially chiral biaryls, we have investigated the cross-coupling of the planar chiral arylhalide chromium tricarbonyl complexes with arylboronic acids. Thus, palladium (0)-mediated Suzuki-Miyaura cross-coupling of planar chiral (2, 6-disubstituted bromobenzene) chromium complexes with o-substituted arylboronic acids gave stereoselectively axially chiral mono Cr(CO)3-complexed biaryls. The axial stereochemistry of the cross-coupling products was found to be largely dependent on the steric bulkiness of ortho substituent of arylboronic acids and reaction conditions. The overall process gives a promising approach for the preparation of both atropisomers stereoselectively starting from a single planar chiral (arene)chromium complex. By utilizing these methodologies, biologically active axially chiral natural products, steganone, korupensamine and axially chiral A-B ring system of vancomycin were stereoselectively synthesized.