Roberts group publishes synthetic chemistry research in Science

MINNEAPOLIS / ST. PAUL (04/25/2024) – The Roberts group recently published a new paper in Science that explores enabling the use of a previously inaccessible functional group for N-heteroaromatic compounds. Science – the flagship journal for the American Association for the Advancement of Science (AAAS) – publishes groundbreaking research across the spectrum of scientific fields. 

N-Heteroaromatic are an important class of molecules which are key to elements of pharmaceutical, agrochemicals and materials. Efficient and innovative methods to make functionalized heteroarenes are needed to make these critical molecules more readily available. One attractive method for the synthesis of N-heteroaromatic compounds would be the use of a N-heteroaryne – an aromatic ring containing a nitrogen atom and a triple bond. N-heteroarynes within 6-membered rings have been used as key intermediates for synthetic chemists, however after 120 years of aryne research the use of 5-membered N-heteroarynes has remained elusive. Notably, a computational model has predicted these 5-membered N-heteroarynes to be “inaccessible”, meaning they cannot be accessed synthetically due to the excessive strain associated with forming a triple bond within a small 5-membered ring.

The Roberts group hypothesized by applying principles of organometallic chemistry, forming 5-membered N-heteroarynes at a metal center would alleviate strain through back-bonding and allow access to this previously inaccessible functional group. In a report which was published in Science, the Roberts group achieved the first synthesis of 7-azaindole-2,3-yne complexes using phosphine-ligated nickel complexes. The complexes were characterized by X-ray crystallography and spectroscopy. Additionally, the complexes showed ambiphilic reactivity, meaning they react with both nucleophiles and electrophiles, making them an exceptionally versatile tool for the synthesis of N-heteroaromatic compounds. This exciting research breakthrough will have important applications in expanding the “chemist’s toolbox” for developing new pharmaceuticals, agrochemicals, and materials, and also provide fundamental insights on accessing synthetically useful strained intermediates.

This new work from the Roberts group was enabled by the National Institutes of Health, and by a multitude of fellowships held by the paper’s collaborators. Fifth-year PhD candidate Erin Plasek is supported by the UMN Doctoral Dissertation Fellowship;  fifth-year student Jenna Humke is supported by the National Science Foundation Graduate Research Fellowship Program; both Plasek and Humke are supported by Department of Chemistry Fourth-Year Excellence Fellowships; and third-year graduate student Sallu Kargbo was supported by the Gleysteen Departmental First Year Fellowship. For leadership excellence of her research program, Courtney Roberts has been awarded the 3M Alumni Professorship, the McKnight Land-Grant Professorship, the Amgen Young Investigator Award, and the Thieme Chemistry Journal Award in the past year alone.

“It is incredibly exciting to see this work, which started out as a few lines in my initial job proposals, come to fruition because of the exceptional team of students and postdocs behind it. We are delighted to finally share this new functional group for 5-membered N-heterocycles with the synthetic community,” Roberts writes.

Founded in 2019, the Roberts group uses inorganic and organometallic chemistry and catalysis to solve fundamental problems in synthetic organic chemistry related to pharmaceuticals, agrochemicals and materials. They have published work related to early transition metal catalysis, photochemical reactions, and inducing regioselectivity in metal-mediated aryne reactions. The group now consists of 14 graduate students, two postdoctoral associates, and one undergraduate researcher from a range of organic and inorganic backgrounds, which allows the team to take a multidisciplinary approach to solving research problems. They value diversity, collaboration, inclusivity, and radical candor in everything they do.