Laboratorium für Organische Chemie, ETH Zurich , Vladimir-Prelog-Weg 3, 8093 Zurich, Switzerland.
Laboratorium für Physikalische Chemie, ETH Zurich , Vladimir-Prelog-Weg 2, 8093 Zurich, Switzerland.
J Am Chem Soc. 2017 Sep 6;139(35):12190-12200. doi: 10.1021/jacs.7b05461. Epub 2017 Aug 15.
Enantiopure alleno-acetylenic cage (AAC) receptors with a resorcin[4]arene scaffold, from which four homochiral alleno-acetylenes converge to shape a cavity closed by a four-fold OH-hydrogen-bonding array, form a highly ordered porous network in the solid state. They enable the complexation and co-crystallization of otherwise non-crystalline small molecules. This paper analyzes the axial conformers of monohalo- and (±)-trans-1,2-dihalocyclohexanes, bound in the interior cavity of the AACs, on the atomic level in the solid state and in solution, accompanied by accurate calculations. The dihedral angles ϑ (X-C(1)-C(2)-X/H) of the axial/diaxial conformers deviate substantially from 180°, down to 144°, accompanied by strong flattening of the ring dihedral angles. Structure optimization of the isolated guest molecules demonstrates that the non-covalent interactions with the host hardly affect the dihedral angles, validating that the host is an ideal means to study the elusive axial/diaxial conformers. X-ray co-crystal structures of AACs further allowed for a detailed investigation, both experimentally and theoretically, on the interplay between space occupancy, guest conformation, and chiral recognition based purely on dispersion forces and weak C-X···π (X = Cl, Br, I) and C-X···||| (acetylene) contacts (X = Cl, Br). The theoretical analysis of the non-covalent interactions between host and guest confirmed the high shape complementarity with fully enveloping dispersive interactions between the binding partners, rationalizing the high degree of enantioselectivity in the previously communicated complexation of (±)-trans-1,2-dimethylcyclohexane. This study also showed that (±)-trans-1,2-dihalocyclohexanes (X = Cl, Br) engage in significant halogen bonding (XB) interactions C-X···||| with the hosts. Slow host-guest exchange on the NMR time scale enabled the characterization of the encapsulated guests in solution, demonstrating that the complexes have identical geometries to those seen in the solid state, with the guests bound in axial/diaxial conformations.
具有间苯二酚[4]芳烃骨架的对映纯烯丙基-乙炔笼（AAC）受体，其中四个手性烯丙基-乙炔从四面汇聚形成一个由四氢氢键阵列封闭的空腔，在固态中形成高度有序的多孔网络。它们能够使原本非晶小分子的络合和共结晶。本文在原子水平上分析了在固态和溶液中结合在 AAC 内部空腔中的单卤代和（±）-反式-1,2-二卤代环己烷的轴向构象，同时进行了精确计算。轴向/双面构象的二面角 ϑ（X-C（1）-C（2）-X/H）明显偏离 180°，降至 144°，同时环二面角明显变平。孤立客体分子的结构优化表明，与主体的非共价相互作用几乎不会影响二面角，验证了主体是研究难以捉摸的轴向/双面构象的理想手段。AAC 的 X 射线共晶结构进一步允许在实验和理论上对空间占有率、客体构象和基于纯色散力和弱 C-X···π（X = Cl、Br、I）和 C-X···|||（乙炔）接触（X = Cl、Br）的手性识别之间的相互作用进行详细研究。主体与客体之间非共价相互作用的理论分析证实了结合伙伴之间完全包裹的分散相互作用具有很高的形状互补性，合理地解释了先前报道的（±）-反式-1,2-二甲基环己烷络合中高度的对映选择性。这项研究还表明，（±）-反式-1,2-二卤代环己烷（X = Cl、Br）与主体发生显著的卤素键（XB）相互作用 C-X···|||。NMR 时间尺度上的主体-客体缓慢交换使溶液中包裹的客体得以表征，证明复合物具有与固态相同的几何形状，客体以轴向/双面构象结合。
