Helical molecules are not only esthetically appealing due to their structural beauty, they also display unique physical properties as a result of their chirality. We describe herein a new approach to "Geländer" oligomers by interlinking two oligomer strands of different length. To compensate for the dimensional mismatch, the longer oligo(benzyl ether) oligomer wraps around the oligophenyl backbone. The new "Geländer" oligomer 1 was assembled in a sequence of functional-group transformations and cross-coupling steps followed by final cyclizations based on nucleophilic substitution reactions, and was fully characterized, including X-ray diffraction analysis. The isolation of pure enantiomers enabled the racemization process to be studied by circular dichroism spectroscopy.

Conceptually and experimentally, a new set of helical model compounds is presented herein that allow correlations between structural features and their expression in the secondary structure to be investigated. A cross-linked oligomer with two strands of mismatching lengths connected in a ladder-type fashion serves as a model system. Compensation for the dimensional mismatch leads to the adoption of a helical arrangement. A strategically placed relay ensures the continuity and uniformity of the helix. Upon exchanging the heteroatomic linkage, the helix responds by increasing or decreasing the torsion of the backbone. Inversion of the relay's substitution pattern causes a distortion of the structure, while maintaining the directionality of the helix. Based on a short synthetic protocol with a modular precursor, four closely related "Geländer" oligomers (Geländer is the German word for bannister) were accessed and fully characterized. XRD analysis for one representative of each helical arrangement and complementary computational studies for the remaining derivatives allowed the impact of the alterations on the secondary structures to be studied. Isolation of pure enantiomers of all new Geländer oligomers provided insight into the racemization kinetics and estimation of the racemization barrier. In silico simulation of the electronic circular dichroism spectra of the model compounds enabled the helicity of the isolated samples to be assigned.

The first enantioselective total syntheses of virosaine A and bubbialidine are described. Key transformations include the formation of a tetracyclic intermediate via an intramolecular aza-Michael addition, generation of a N-hydroxy-pyrrolidine through a Cope elimination and an intramolecular [1,3]-dipolar cycloaddition to generate a complex 7-oxa-1-azabicyclo[3.2.1]octane ring system.

Macrocycle 1 is assembled as smallest member of a series of “Geländer” oligomers with a conjugated banister comprising exclusively sp2‐ and sp‐hybridized carbon atoms. The synthesis of 1 is based on an acetylene scaffolding approach, comprising Sonogashira cross‐coupling reactions in combination with protection group strategies and a final cyclization based on an oxidative acetylene coupling using Eglinton‐Breslow reaction conditions. Macrocycle 1 serves as model compound for the investigation of the structural integrity of the strained 1,3‐diyne subunit. An enhanced reactivity of the strained 1,3‐diyne subunit is documented by its engagement in Huisgen's (2+3) cycloaddition when exposed to an azide at elevated temperature. Both structures, macrocycle 1 and cycloaddition‐product 2, are fully characterized including their solid‐state structure obtained by X‐ray diffraction analysis.

This paper highlights a new concept on how to induce chirality in a hexaphenyl Geländer‐type system. Bridging a terphenyl backbone with a considerably longer benzyl ether oligomer enforces a continuous twist of the molecule, while preventing an achiral meso form. By highlighting cross‐coupling strategies and explored synthetic pathways, this report aims to serve as an Ariadne's thread for the synthesis of precisely functionalized, complex polyaromatic systems. The synthetic challenges and considerations required to access the designed target are outlined and solutions to each step of the assembly are presented. Encountered isomerizations are discussed as much as synthetic tools to access highly functionalized intermediates with multiorthogonal moieties. A strong focus is made on the employment of Suzuki–Miyaura protocols for the targeted connection of polyaromatic fragments and ultimately the desired oligomeric structure.