31-Aug-2015 - Princeton University

Turning alcohols into alkylating agents

Taking a cue from nature

Researchers at Princeton have developed a dual catalyst system that directly installs alkyl groups onto heteroarenes. The new reaction uses simple and abundant alcohols and offers a milder and more widely applicable alternative to existing strategies.

The reported transformation is the first to successfully use alcohols as reagents in alkylation reaction. The unique reaction was actually discovered by chance, said David MacMillan, the James S. McDonnell Distinguished University Professor of Chemistry who led the work.

The research team was exploring alcohol additions when a test reaction revealed a surprising product that lacked the alcohol group. After further investigation, the team realized that the reaction underwent a well-known process in biochemistry, called spin center shift, which is involved in fundamental pathways such as DNA biosynthesis, but has rarely been seen in organic synthesis.

The researchers were able to mimic this natural phenomenon by using two types of catalysis in combination. The first catalyst, known as an iridium photocatalyst, initiates the reaction by taking a single electron from the second catalyst, a compound called a thiol, to form a key intermediate. That intermediate - a thiol radical - is uniquely capable of pulling a hydrogen atom off of the starting alcohol, cleaving a typically strong C-H bond. Breaking this bond reveals an alcohol species that reacts with the heteroarene and then follows the spin center shift pathway found in nature to form the final product.

Using their method, the researchers were able to synthesize a wide range of products, highlighting the incorporation of methyl groups. MacMillan and coworkers also demonstrated the efficient alkylation of two pharmaceutical compounds, showing its utility for late-stage alkylation.

Facts, background information, dossiers
  • Princeton University
  • organocatalysis
  • C-Alkylation
  • spin center shift
  • photocatalysis
  • heteroarenes
More about Princeton University
  • News

    When a band falls flat: Searching for flatness in materials

    The world’s first catalog of flat band materials, published in Nature journal, could reduce the serendipity in the search for new materials with exotic quantum properties, such as magnetism and superconductivity, with applications in memory devices or in long-range dissipationless transport ... more

    Researchers measure the breakup of a single chemical bond

    The team used a high-resolution atomic force microscope (AFM) operating in a controlled environment at Princeton’s Imaging and Analysis Center. The AFM probe, whose tip ends in a single copper atom, was moved gradually closer to the iron-carbon bond until it was ruptured. The researchers me ... more

    New route to chemically recyclable plastics

    As the planet's burden of rubber and plastic trash rises unabated, scientists increasingly look to the promise of closed-loop recycling to reduce waste. A team of researchers at Princeton's Department of Chemistry announces the discovery of a new polybutadiene molecule - from a material kno ... more

  • Videos

    “Perfect Glass”

    Princeton University researchers have developed a computational model for creating a "perfect glass" that never crystallizes — even at absolute zero. The molecular structure of a glass suggests it should have liquid properties, yet it behaves with the rigidity of a solid. The researchers ex ... more