A reaction that removes sulfur, nitrogen or oxygen atoms from six-membered rings using only blue light

Diversification of piperidine. (A) Peripheral functionalization, skeletal remodeling. (B) A selection of examples of ring contractions using piperidine frameworks. (C) Seminal Report of Seebach and coworkers unusual THIQ-ring contraction (20). Surez and coworkers reported a contraction of carbohydrates (21). (E) Norrish type 2 approach to piperidine-skeletal framework modification (this research). Credit: Science (2021). DOI: 10.1126/science.abi7183
Merck & Co. Inc. and a team of chemists from the University of California, Berkeley have developed a method that removes one sulfur, nitrogen, or oxygen atom from a six-membered ring with only a blue beam. The group published their research in Science, which describes the reaction and its potential uses in various applications.

Chemists have discovered ways to manipulate carbon rings used in the creation of a variety of pharmaceutical and agricultural products. However, most of these are complicated and difficult to execute. These processes also require a lot energy. Researchers have now found a way to break the CS CO and CN bonds within saturated heterocycle rings to remove one atom. They only needed a blue light to do this. Afterward, the ring recloses with one atom.

The researchers must first expose the aromatic ketone group, which is attached to a heterocycle, to a blue LED light in order to perform a reaction. This triggers a Norrish reaction. A carbon-heteroatom bond will be cleaved. The ring will then open and an atom will be ejected. It creates a core radical. This is why it works. The second stage of the reaction is the closure of the ring. This, according to the team, is similar to a Mannich reaction. The light wavelength must match the carbonyl in their starting material for the reaction to be successful. The structure was simply modified so that it left a five-membered circle.

Researchers note that the reaction, despite being simple, is an important step in manipulating the building blocks for medicinal chemistry. The researchers also note that the reaction can be combined with other reactions, allowing for multiple modifications at once. The effectiveness of the reaction was demonstrated by them using it to modify several well-known drugs such as mefloquine or rimiterol. Their new goal is to add an aromatic ketone to a saturated heterocycle.

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Further information: Justin Jurczyk and colleagues, Photomediated Ring Contraction of Saturated Heterocycles, Science (2021). Information from Science Justin Jurczyk and colleagues, Photomediated Ring Contraction of Saturated Hecycles, (2021). DOI: 10.1126/science.abi7183

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