Carbon-to-nitrogen single-atom transmutation of azaarenes.

When searching for the ideal molecule to fill a particular functional role (for example, a medicine), the difference between success and failure can often come down to a single atom. Replacing an aromatic carbon atom with a nitrogen atom would be enabling in the discovery of potential medicines, but only indirect means exist to make such C-to-N transmutations, typically by parallel synthesis. Here, we report a transformation that enables the direct conversion of a heteroaromatic carbon atom into a nitrogen atom, turning quinolines into quinazolines.

Single-atom logic for heterocycle editing.

Medicinal chemistry continues to be impacted by new synthetic methods. Particularly sought after, especially at the drug discovery stage, is the ability to enact the desired chemical transformations in a concise and chemospecific fashion. To this end, the field of organic synthesis has become captivated by the idea of 'molecular editing'-to rapidly build onto, change or prune molecules one atom at a time using transformations that are mild and selective enough to be employed at the late stages of a synthetic sequence.

Scaffold hopping by net photochemical carbon deletion of azaarenes.

Discovery chemists routinely identify purpose-tailored molecules through an iterative structural optimization approach, but the preparation of each successive candidate in a compound series can rarely be conducted in a manner matching their thought process. This is because many of the necessary chemical transformations required to modify compound cores in a straightforward fashion are not applicable in complex contexts. We report a method that addresses one facet of this problem by allowing chemists to hop directly between chemically distinct heteroaromatic scaffolds.