Impact of C-H Cross-Coupling Reactions in the One-Step Retrosynthesis of Drug Molecules.

Pharmaceutical synthesis requires a diversity of chemical reactions. The discovery of new reactions enable novel retrosynthetic disconnections, potentially expediting access to complex molecules. This Synopsis demonstrates the use of enumerative combinatorics to find impactful underdeveloped reactions for drug synthesis.

Radical Chlorination of Non-Resonant Heterobenzylic C-H Bonds and High-Throughput Diversification of Heterocycles.

Site-selective functionalization of the heterobenzylic C(sp)-H bonds of pyridines and related heteroaromatic compounds presents challenges associated with the basic nitrogen atom and the variable reactivity among different positions on the heteroaromatic ring. Methods for functionalization of 2- and 4-alkylpyridines are increasingly available through polar pathways that leverage resonance stabilization of charge build-up at these positions. In contrast, functionalization of 3-alkylpyridines is largely inaccessible.

Fluorine Labeling of -Phenylenes to Facilitate Conformational Analysis.

H NMR spectroscopy is a powerful tool for the conformational analysis of -phenylene foldamers in solution. However, as -phenylenes are integrated into ever more complex systems, we are reaching the limits of what can be analyzed by H- and C-based NMR techniques. Here, we explore fluorine labeling of -phenylene oligomers for analysis by F NMR spectroscopy.