Chiral Hexahalogenated 4,4′-Bipyridines

The preparation of 27 isomers of chiral hexahalogeno-4,4′-bipyridines by means of two complementary methods is described. The first one is convergent and based on the LDA-induced 4,4′-dimerization of trihalopyridines, whereas the second method is divergent and achieved through regioselective halogenation reactions of 4,4′-bipyridine-2,2′-diones. Iodine in 2,2′-positions of the 4,4′-bipyridines was introduced by a copper-catalyzed Finkelstein reaction (Buchwald procedure) performed on 2,2′-dibromo derivatives. Selected compounds of this new family of atropisomeric 4,4′-bipyridines were enantioseparated by high performance liquid chromatography on chiral stationary phases, and the absolute configurations of the separated enantiomers were assigned by using X-ray diffraction analysis. The latter revealed that various halogen bond types are responsible for crystal cohesion.本文报道了采用两种互补方法合成手性六卤代-4,4′-联吡啶（hexahalogeno-4,4′-bipyridines）的27种异构体的研究工作。第一种方法为收敛式合成，基于LDA诱导的三卤代吡啶（trihalopyridines）的4,4′-二聚反应；第二种方法为发散式合成，通过4,4′-联吡啶-2,2′-二酮的区域选择性卤代反应实现。在4,4′-联吡啶的2,2′-位引入碘原子，可通过对2,2′-二溴代衍生物实施铜催化的芬克尔斯坦反应（Finkelstein reaction，布赫瓦尔德操作法）完成。本研究选取该新型阻转异构4,4′-联吡啶家族中的部分化合物，采用手性固定相（chiral stationary phases）高效液相色谱法进行对映体拆分，并通过X射线衍射分析确定了拆分所得对映体的绝对构型。该分析结果表明，多种类型的卤键（halogen bond）是晶体凝聚的关键作用力。