Chiral carbon-rich architectures: from "Geländer" molecules to pyrenophanes

Topological beauty is rooted in the intrinsic chirality of molecules bearing unique chiroptical properties. The combination of topological beauty with chemistry opens up a challenging yet esthetically and intellectually pleasing field of research. However the translation of such concepts, particularly those with peculiar or strained architectures into a molecular design is not a straight-forward task. Scientists have however overcome this complexity, through the development of diverse synthetic approaches to build challenging, fascinating and topologically unique structures.
This cumulative PhD thesis follows on and expands on from fundamental work established on "Geländer" molecules. This thesis is divided into two main projects. The first section focuses on banister-like structures, which have been coined the name "Geländer" helices due to its similarity in shape to the banister of a spiral staircase. The first publication in Chemical Science (2018) discusses the design and synthesis of a tightly packed all-carbon Geländer structure. The dynamic behavior of the different chiral cyclophanes were analyzed by HPLC and ECD techniques and they clearly confirmed that our concept of a more compressed structural design enhances the racemization barrier tremendously. The ensuing manuscript, prepared for submission to The Journal of Organic Chemistry (2019), expands on the concept of fine-tuning the helical structure through targeted changes in the macrocycle. We envisioned the synthesis of the sulfone functionalized Geländer helices, in which steric bulkiness is introduced in the bridging scaffolds. The effect of enhanced steric hindrance on the interconversion process following Mislow’s Euclidean rubber glove enantiomerization pathway and the thermodynamic studies are discussed. The synthesis of the sulfone functionalized Geländer molecule enabled the synthesis of a further banister-like structure with full π-conjugation. Utilizing the literature known Ramberg-Bäcklund reaction, the sulfone functionality could be transformed into olefinic groups, achieving one of the initial goals of Geländer model compounds with electron delocalization over the whole structure. In addition to the many isomers already possible in the Geländer structures, the introduction of the olefinic groups introduced several more possible isomers, rendering the purification of the diasteromers tedious. Through use of HPLC and a reversed stationary phase the various Geländer isomers could be purified, allowing for full characterization of the racemization behaviors, UV-Vis and ECD spectroscopy and the crystal structures to be solved.
The second project of the thesis discusses the synthesis and analysis of a basked-shaped all-carbon macrocycle, which was published in The Journal of Organic Chemistry (2019). We presented a novel and elegant synthesis of a chiral all-carbon pyrenophane structure. The two enantiomers were separated using HPLC technique equipped with a chiral stationary phase. The chiroptical properties and thermal stability upon racemization are discussed in the publication. The supplementary information of all the manuscripts have been added for the reader's convenience and are given at the end of this thesis.
Preceding these three manuscripts, the reader will find a tutorial review entitled "Introducing Tailor-Made Chirality in Carbon-Rich Topological Architectures" which has been prepared for submission in the Chemical Society Reviews (2019). This tutorial article illustrates the rise of chiral induced structures and their synthetic strategies are categorized into three main classes - I) achiral building blocks, II) chiral building blocks and III) non-covalent interactions. The selected structures in this article, which are driven by their arrangement in 3-D space and not by a stereogenic or chiral center, give a clear systematic overview of the various synthetic approaches to construct chiral carbon-rich structures - including the cyclophanes realized in this thesis. The review connects the topic of the thesis with the wider world of chiral carbon-rich architectures.