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New amination chemistry brought to light

Photogenerated radical cations yield amines previously impossible to make

by Bethany Halford
February 16, 2017 | A version of this story appeared in Volume 95, Issue 8

a hydroamination reaction

Flashes of light help chemists at Princeton University and Bristol-Myers Squibb drive the hydroaminations of olefins to produce substituted amines. The light-powered reaction gives chemists another tool for installing amines in drugs and other biologically important molecules.

The new hydroamination is noteworthy for its intermolecular reactivity, its use of unactivated olefin substrates, its toleration of several different functional groups, and its regioselectivity for anti-Markovnikov amine products—wherein the new C–N bond forms on the less substituted carbon of the olefin (Science 2017, DOI: 10.1126/science.aal3010). Most other examples of hydroaminations result in products with the opposite, Markovnikov regiochemistry. What’s more, the new reaction can produce highly substituted amines (such as in the example shown) that are impossible to make any other way.

In the reaction, irradiation of a secondary alkyl amine in the presence of an iridium catalyst and a thiol cocatalyst yields an aminium radical cation intermediate. This species is responsible for the reaction’s anti-Markovnikov regiochemistry and highly substituted products, explains Robert Knowles, who led the research ­effort. “These alkyl aminium radical cations are highly reactive and will add to many olefin classes with extraordinarily fast rates, allowing us to achieve these types of intermolecular hydroaminations.” he says.

“Knowles came up with an elegant approach to what was really an unsolved problem,” comments Kami L. Hull, an expert in anti-Markovnikov hydrofunctionalization at the University of Illinois, Urbana-Champaign. Previous examples of anti-Markovnikov hydroaminations, she points out, either required activated olefins or directing groups, or produced stoichiometric amounts of unwanted by-products. Furthermore, Hull adds, Knowles’s olefin substrates are so energetically stable that they wouldn’t react without his photocatalytic approach, which really expands what chemists can do with this reaction.


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