Synthesis, Crystal Structure, and Resolution of [10](1,6)Pyrenophane: An Inherently Chiral [n]Cyclophane

A synthetic approach to a set of three inherently chiral
[n]­cyclophanes, [n]­(1,6)­pyrenophanes
(29a–c, n = 8–10)
was investigated. Progress toward 29a was thwarted by
the failure of the key dithiacyclophane-forming reaction. For the
next higher homologue, the synthesis was completed, but the desired
[9]­(1,6)­pyrenophane (29b) could only be partially separated
from an isomeric pyrenophane, [9]­(1,8)­pyrenophane (28b), and an unidentified byproduct. Work aimed at the synthesis of
the next higher homologue resulted in the isolation of a 7:4 mixture
of [10]­(1,8)­pyrenophane (28c) and [10]­(1,6)­pyrenophane
(29c), which could not be separated by column chromatography
or crystallization. However, single-crystal X-ray structures of 28c and 29c were obtained after manual separation
of two crystals with different morphologies from the same batch of
crystals obtained from the 7:4 mixture of 28c and 29c. The pyrene system of 29c was found to have
a gentle end-to-end bend as well as a significant longitudinal twist.
Short intermolecular C­(sp3)–H···π
contacts (2.64 to 2.76 Å) between H-atoms on the bridge and the
centroids of three of the four six-membered rings of the pyrene system
of a neighboring pyrenophane of like chirality give rise to the formation
of single enantiomer columns. From a DNMR study of the mixture of 28c and 29c, the bridge in [10]­(1,8)­pyrenophane
(28c) was found to undergo a conformational flip from
one side of the pyrene system to the other with ΔG⧧ = 14.9 ± 0.2 kcal/mol.
A two-stage preparative HPLC protocol was subsequently developed for
the separation of 28c and 29c (Chiralpak
AD-H column) and then the enantiomers of 29c (Chiralcel
OJ-H column). This enabled the measurement of their optical rotations
and CD spectra.

本研究探讨了三种本质手性[n]－环状芳族化合物，[n]－(1,6)－芘诺烷（29a–c，n = 8–10）的合成途径。在向29a合成进军的道路上，由于关键二硫代环状芳族形成反应的失败而遭遇挫折。对于更高同系物，合成工作得以完成，但期望中的[9]－(1,6)－芘诺烷（29b）只能部分地从同分异构体芘诺烷[9]－(1,8)－芘诺烷（28b）及一种未知的副产物中分离出来。旨在合成更高同系物的努力最终从[10]－(1,8)－芘诺烷（28c）和[10]－(1,6)－芘诺烷（29c）的7:4混合物中分离出了单一晶体。然而，这些化合物无法通过柱层析或结晶进行分离。尽管如此，在从同一批7:4混合物中手动分离出两种不同形态的晶体之后，成功获得了28c和29c的单晶X射线结构。29c的芘诺烷系统中发现存在从一端至另一端的轻微弯曲以及显著的纵向扭曲。短程分子间C(sp3)–H···π接触（2.64至2.76 Å）存在于桥上的氢原子与相邻同手性芘诺烷系统中四个六元环的质心之间，从而导致了单一对映异构体柱的形成。通过DNMR对28c和29c混合物的研究发现，[10]－(1,8)－芘诺烷（28c）中的桥结构在ΔG⧧ = 14.9 ± 0.2 kcal/mol下，从芘诺烷系统的一侧翻转到另一侧。随后，开发了一种两阶段的制备型高效液相色谱（HPLC）方案，用于28c和29c（Chiralpak AD-H柱）以及29c的对映异构体（Chiralcel OJ-H柱）的分离，从而能够测量其旋光度和圆二色光谱。