The activation of typically unreactive aromatic C–H bonds by transition-metal catalysis has been receiving increased attention from the synthetic chemistry community in recent years. Advances in this area have enabled direct and site-selective modification of aromatic rings without the need for pre-functionalization. Accordingly, these techniques have found broad application in many fields, including the construction of extended π-systems for use in materials science. This review will discuss recent reports of C–H activation reactions applied toward the synthesis of π-extended functional materials.

Molecular nanocarbons containing heptagonal rings have attracted increasing interest due to their dynamic behavior, electronic properties, aromaticity, and solid‐state packing. Heptagon incorporation can not only induce negative curvature within nanocarbon scaffolds, but also confer significantly altered properties through interaction with adjacent non‐hexagonal rings. Despite the disclosure of several beautiful examples in recent years, synthetic strategies toward heptagon‐embedded molecular nanocarbons remain relatively limited due to the intrinsic challenges of heptagon formation and incorporation into polyarene frameworks. In this Review, recent advances in solution‐mediated and surface‐assisted synthesis of heptagon‐containing molecular nanocarbons, as well as the intriguing properties of these frameworks, will be discussed.

Scheme 4. Synthesis of azulene-embedded nanocarbons 12 and 15. (MsOH = methanesulfonic acid).

Using a specially designed magnesium metallating manifold, combining kinetically activated TMP amide base with a sterically amplified β-diketiminate ligand, this study has established a new regioselective strategy for magnesiation of challenging N-heterocyclic molecules. The broad scope of the approach is illustrated through reactions of pyrazine, triazoles and substituted pyridines by isolation and structural elucidation of their magnesiated intermediates.

In analogy to biosynthetic pathways leading to bioactive natural products, synthetic fermentation generates mixtures of molecules from simple building blocks under aqueous, biocompatible conditions, allowing the resulting cultures to be directly screened for biological activity. In this work, a novel β-peptide antibiotic was successfully identified using the synthetic fermentation platform. Phenotypic screening was carried out in an initially random fashion, allowing simple identification of active cultures. Subsequent deconvolution, focused screening, and structure−activity relationship studies led to the identification of a potent antimicrobial peptide, showing strong selectivity for our model system Bacillus subtilis over human HEK293 cells. To determine the antibacterial mechanism of action, a peptide probe bearing a photoaffinity tag was readily synthesized through the use of appropriate synthetic fermentation building blocks and utilized for target identification using a quantitative mass spectrometry-based strategy. The chemoproteomic approach led to the identification of a number of bacterial membrane proteins as prospective targets. These findings were validated through binding affinity studies with penicillin-binding protein 4 using microscale thermophoresis, with the bioactive peptide showing a dissociation constant (K d ) in the nanomolar range. Through these efforts, we provide a proof of concept for the synthetic fermentation approach presented here as a new strategy for the phenotypic discovery of novel bioactive compounds.