Mechanical Stabilization of Helical Chirality in a Macrocyclic Oligothiophene

We introduce a design
principle to stabilize helically chiral structures
from an achiral tetrasubstituted [2.2]­paracyclophane by integrating
it into a macrocycle. The [2.2]­paracyclophane introduces a three-dimensional
perturbation into a nearly planar macrocyclic oligothiophene. The
resulting helical structure is stabilized by two bulky substituents
installed on the [2.2]­paracyclophane unit. The increased enantiomerization
barrier enabled the separation of both enantiomers. The synthesis
of the target helical macrocycle 1 involves a sequence
of halogenation and cross-coupling steps and a high-dilution strategy
to close the macrocycle. Substituents tuning the energy of the enantiomerization
process can be introduced in the last steps of the synthesis. The
chiral target compound 1 was fully characterized by NMR
spectroscopy and mass spectrometry. The absolute configurations of
the isolated enantiomers were assigned by comparing the data of circular
dichroism spectroscopy with TD-DFT calculations. The enantiomerization
dynamics was studied by dynamic HPLC and variable-temperature 2D exchange
spectroscopy and supported by quantum-chemical calculations.

我们提出了一种设计原则，可通过将非手性四取代[2.2]对环芳烷（[2.2]­paracyclophane）整合到大环（macrocycle）中，以稳定螺旋手性结构。该[2.2]对环芳烷可向近乎平面的大环寡噻吩（macrocyclic oligothiophene）引入三维扰动。所得到的螺旋结构可通过连接在[2.2]对环芳烷单元上的两个大体积取代基实现稳定。提升的对映异构化能垒使得两种对映异构体得以分离。目标螺旋大环化合物1的合成涉及卤化、交叉偶联等多步反应，以及用于大环成环的高稀释策略。可在合成的最后阶段引入取代基，以调控对映异构化过程的能量。手性目标化合物1已通过核磁共振（NMR）波谱与质谱分析法完成全面表征。分离得到的对映异构体的绝对构型，通过将圆二色性（circular dichroism）光谱数据与含时密度泛函理论（TD-DFT）计算结果进行比对得以确定。对映异构化动力学通过动态高效液相色谱（HPLC）与变温二维交换光谱法展开研究，并通过量子化学计算予以佐证。