Researchers Develop Simple Method for Synthesizing Aryne Precursors

A team of researchers at the University of Minnesota has developed a groundbreaking method for synthesizing blue light-responsive aryne precursors from carboxylic acids in a single step. Their findings, published on November 11, 2025, in the journal Nature, promise to enhance the accessibility and versatility of these valuable organic intermediates in pharmaceutical and agricultural chemistry.

Arynes are highly reactive compounds characterized by a triple bond within an aromatic ring. Their unique structure allows them to readily bond with various functional groups, making them essential in synthesizing complex aromatic molecules. Despite their potential, synthetic chemists have traditionally avoided arynes due to the challenges associated with their synthesis.

The new method developed by the University of Minnesota team simplifies the process of generating arynes, overcoming historical limitations. Conventional techniques typically require harsh conditions, including strong bases to strip protons from C–H bonds, followed by halide elimination. These methods are unsuitable for sensitive functional groups and have hindered the broader application of arynes in organic reactions.

The research team aimed to address these challenges by exploring the use of o-iodoniobenzoates as precursors for aryne synthesis. They discovered that by modifying these precursors with isopropoxy groups, they could significantly improve their solubility and reduce unwanted side reactions. The introduction of additional substituents adjacent to the carboxylate group enabled the activation of aryne precursors through either blue light or mild heat (up to 100 °C).

The findings reveal that the heat activation is driven by a field effect, where the electronic field created by nearby functional groups promotes decarboxylation. In contrast, blue light activation (at a wavelength of 398 nm) excites the molecule, leading to the release of carbon dioxide and the formation of arynes.

This innovative one-pot synthesis method represents a significant advancement, allowing for the creation of a wide range of aryne derivatives from readily available starting materials. The researchers emphasize that the approach is compatible with various functional groups, which could simplify the synthesis of complex aromatic compounds used in pharmaceuticals and agrochemicals.

The potential implications of this research extend beyond academic interest; by unlocking access to new aryne precursors, the study opens avenues for exploring previously uncharted chemical territories. As these compounds gain traction in synthetic chemistry, the findings may lead to enhanced drug discovery processes and improved agricultural solutions.

The study’s author, Sanjukta Mondal, alongside editors such as Lisa Lock and reviewers like Robert Egan, have ensured the rigorous vetting of this research, contributing to the credibility of the findings. The research conducted by the team, led by Chris M. Seong, marks an important milestone in the field of synthetic chemistry, positioning arynes as more accessible tools for researchers.

For those interested in the evolving landscape of synthetic organic chemistry, this study serves as a reminder of the importance of innovation in addressing long-standing challenges. The ability to synthesize aryne precursors more efficiently could have far-reaching effects in various scientific domains.

As the scientific community continues to explore the potential of these findings, it becomes clear that advancements in synthesis techniques can open doors to new possibilities in drug development and agricultural chemistry.