Yagami Ryota, Xu Wei, Kobayashi Toi, Nagata Yuuya, Kumagai Naoya
Graduate School of Pharmaceutical Sciences, Keio University 1-5-30 Shibakoen, Minato-ku Tokyo 105-8512 Japan
Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University Hokkaido Kita 21, Nishi 10, Kita-ku Sapporo Hokkaido 001-0021 Japan.
Chem Sci. 2025 May 20;16(24):10714-10721. doi: 10.1039/d5sc02937f. eCollection 2025 Jun 18.
Chiral macrocycles are attracting growing interest due to their broad applicability as ligands in asymmetric catalysis and as host molecules for chiral recognition. Robustness and high thermodynamic stability can be effectively achieved by strategically linking aromatic panels to construct an axially chiral macrocyclic framework. Cyclic concatenation of four quinoline units affords a fully sp-hybridized, non-planar macrocycle featuring four inwardly oriented, coordinatively active pyridyl nitrogen atoms. The previously reported tetramer TEtraQuinoline (TEQ) exhibits head-to-tail connectivity of its quinoline units, affording an achiral architecture possessing symmetry. Herein, we report the design and synthesis of -TEtraQuinoline (-TEQ), an inherently chiral analogue featuring head-to-head connectivity at the 2,2'- and 8,8'-positions, which gives rise to a -symmetric architecture. Detailed comparative investigations of the connectivity isomers -TEQ and TEQ revealed an array of distinct characteristics, including the overall architecture, intrinsic macrocyclic strain, spatial orientation of nitrogen lone pairs, thermodynamic stability, racemisation behaviour, metal complex stability, and circularly polarised luminescence.
手性大环化合物因其作为不对称催化中的配体以及手性识别的主体分子具有广泛适用性而越来越受到关注。通过策略性地连接芳环构建轴向手性大环骨架，可以有效地实现其稳定性和高热力学稳定性。四个喹啉单元的环状连接提供了一个完全sp杂化的非平面大环，其具有四个向内取向的、具有配位活性的吡啶氮原子。先前报道的四聚体四喹啉（TEQ）展示了其喹啉单元的头对尾连接方式，形成了一个具有对称性的非手性结构。在此，我们报道了-四喹啉（-TEQ）的设计与合成，它是一种固有的手性类似物，在2,2'-和8,8'-位置具有头对头连接，从而产生一种对称结构。对连接异构体-TEQ和TEQ进行的详细比较研究揭示了一系列不同的特性，包括整体结构、内在大环张力、氮孤对电子的空间取向、热力学稳定性、消旋行为、金属配合物稳定性以及圆偏振发光。
