The Power of Macrocyclic Chemistry: Delving into Unexplored Structures of Conjugated Rings

The following PhD thesis covers the research inquiries that I performed in the group of Prof. Dr. Marcel Mayor at the University of Basel from 2018 to 2022. During the course of the recent past years, various organic chemistry projects were investigated, involving multistep synthesis, structural characterization and in-depth spectroscopic analysis of functional organic molecules. While the individual chapters of the thesis might seem unrelated at a first glance, they share a core structural feature of organic chemistry: Macrocycles. The fundamental base of the explored structures involves radially and planarly pi-conjugated carbon-based macrocycles, which are known to exhibit remarkable optoelectronic properties. Conjugated macrocycles are thus attractive candidates to study fundamental questions and represent attractive molecules for the application in various technological fields, making the exploration of novel ring structures an intriguing and exciting research field.
In an initial introductory part (Introduction), the history of the discovery and structural investigation of benzene will be elucidated, elaborating how it eventually lead to the huge and fascinating research topic of conjugated macrocycles. After covering the pioneering work on various (anti)aromatic [n]annulenes, the story will move towards more complex planarly conjugated macrocycles, followed by recently published radially conjugated macrocycles. Thereby the focus will be laid on the unique optoelectronic properties of selected examples. In a final part, the potential applications of various macrocyclic structures will be illuminated, highlighting the importance of future research inquiries regarding macrocyclic chemistry. This section by no means envisions lying out a comprehensive overview of the state-of-the-art, but aims at providing a historical and chemical context, in which the three main chapters reside.
In the first chapter (Chapter I: Inducing Axial Chirality by a Tight Macrocycle), the chemistry of chromophores will be unraveled and the importance of developing functional molecules with chiroptical properties will be highlighted. Subsequently, our novel macrocyclic rigid framework bearing four mounting points for achiral chromophores of choice will be discussed. The structural constraints of a narrow macrocycle fixes four chromophores in space and places them within a chiral environment. Thus, achiral chromophores can be equipped with chiroptical properties, owing to the optical stability provided by the tight macrocycle. Additionally, the non parallel arrangement of the chromophores enables exciton coupling, which not only allows to determine the absolute configuration but also massively enhances the Cotton effects in the circular dichroism of the chromophore’s transition. Using 6-methoxynaphthalene as a model chromophore, we synthesized and fully characterized the designed framework and demonstrate the effectiveness of the scaffold. In collaboration with Prof. Dr. Stefan Bernhard, we also demonstrate that the chromophore’s fluorescence gains significant luminescence dissymmetry, despite the inherent lack of chirality of the chromophore. We thus believe this framework to be a viable option to diversify chiral materials, which certainly incentivizes its application for various chromophores.
In the second chapter (Chapter II: Macrocyclic pseudo-meta Substituted [2.2]Paracyclophanes), [2.2]paracyclophanes (PCPs) will be introduced as versatile building blocks for incorporation in functional molecules. The main focus will be laid upon twofold substituted pseudo-ortho, pseudo-para and pseudo-meta PCPs and their implementation into conjugated macrocycles. Based on recent experimental evidence by our research group, demonstrating constructive quantum interference in pseudo-meta PCPs, we figured they might be the ideal candidates for embedding into macrocycles. Given the angle between its substituents, its inherent planar chirality and efficient conjugation, pseudo-meta PCPs should be the ideal corner unit for macrocyclization reactions, equip the macrocycle with chiroptical properties and enable thorough through-space conjugation. We thus synthesized and fully characterized four enantiopure polygon-shaped macrocyclic 1,3-butadiyne linked pseudo-meta PCPs. The obtained structures display unprecedented high molar circular dichroism values for all carbon macrocycles, which partially increases non-linearly with regards of the number of PCP subunits. By analysis of key reference compounds, we also demonstrate that the structures are fully conjugated and display polymer-like conjugation lengths. In a concluding part, we further show that the 1,3-butadiynes can be transformed into thiophenes using heterocyclization conditions and highlight the potential of studying global (anti)aromatic ring currents in these thoroughly conjugated systems. The remarkable properties of the studied macrocycles surely motivate future chemists to incorporate pseudo-meta PCPs within various conjugated structures.
In the third chapter (Chapter III: Novel Approach Towards Armchair Carbon Nanotubes), the discovery of carbon nanotubes (CNTs) bearing astonishing mechanical and electrical properties will be presented. With the inherent disadvantages of typical top-down strategies for their synthesis, the necessity for novel bottom-up approaches for the production of CNTs with defined lengths and diameters will be further introduced. Although segments of zigzag and armchair CNTs are nowadays known and accessible reliably using novel synthetic methodologies, their elongation into actual tubes has proven to be troublesome. Based on a recently developed strategy to synthesize graphene sheets through benzannulations and Scholl oxidations on a poly(p-phenylene ethynylene) intermediate, we envisioned to adapt the same synthesis for the production of armchair CNTs. By developing a six-step reaction sequence benefiting from a key Sonogashira coupling as macrocyclization strategy, we were able to access the final CNT precursor in a reliable fashion. The final Scholl reaction involving the formation of 72 carbon-carbon bonds was so far unsuccessful. However, we hereby show that this strategy is a viable option for the successful bottom-up synthesis of armchair CNTs.
In a final summarizing and concluding chapter (Summary and Conclusion), the main findings of the thesis will be recapitulated and brought into the context of potential future opportunities with the hope to inspire future organic chemists.