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.

本文详述了通过两种互补策略制备27种手性六卤代-4,4′-联吡啶（chiral hexahalogeno-4,4′-bipyridines）异构体的方法。第一种为汇聚式合成策略，基于LDA诱导的三卤代吡啶4,4′-二聚反应；第二种为发散式合成策略，通过对4,4′-联吡啶-2,2′-二酮进行区域选择性卤代反应完成。针对4,4′-联吡啶2,2′-位的碘原子引入，我们以2,2′-二溴代衍生物为底物，采用铜催化的芬克尔斯坦反应（布赫瓦尔德操作法）实现转化。针对这一类新型阻转异构4,4′-联吡啶（atropisomeric 4,4′-bipyridines）化合物，我们通过手性固定相高效液相色谱法对部分目标产物进行了对映体拆分，并借助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，多种卤键类型是晶体凝聚的关键作用力。