In a recent research collaboration between Hokkaido University and the University of Shizuoka, researchers took exciting strides in that direction. In each of these projects, they’ve discovered some exciting selective transformations on carboxylic acids. Prelude Associate Professor Hiroki Hayashi from WPI-ICReDD at Hokkaido University and Assistant Professor Kenji Yamashita from the University of Shizuoka have recently made an exciting discovery. They investigated a new activation mode of ubiquitous organic compounds with ground-breaking computational methods. Their results demonstrate the promise of adopting xanthone as a cost-effective photocatalyst. This highly productive and innovative triggering strategy can efficiently accelerate and/or control hydrogen atom transfer (HAT) processes.
Carboxylic acids have been recently lauded for their widespread occurrence in bioactive organic molecules and commercial availability as chemical building blocks. The research team focused on these properties to create a faster, simpler, and more effective process to convert carboxylic acids. They did this via selective photocatalytic hydrogen atom transfer (HAT). To see just how versatile xanthone can be, just take a look at their work. Besides that, it expands the frontier for wide-ranging applications in organic synthesis.
Effective Collaboration and Research Approach
The experimental-computational collaboration between Hayashi and Yamashita reveals how experimental and computational techniques can synergistically advance cutting-edge chemical research toward long overdue progress. They used an Activation-First Reaction (AFIR) approach to predict reaction pathways and experimentally validated their predicted pathways to corroborate their findings.
“Collaborating with the team in Shizuoka to explore a new activation mode of carboxylic acids through computational approaches was an excellent experience,” said Hayashi. “It’s especially meaningful to me that the AFIR method has demonstrated its utility as a predictive tool beyond ICReDD. I hope this computational strategy will continue to drive new advances in reaction development.”
This work exemplifies the critical importance of advanced computational strategies to modern chemistry. Additionally, it provides a template to inform and inspire upcoming basic research toward reaction mechanisms. To their surprise, they discovered that the xanthone exhibited extraordinary substrate versatility. Such selectivity allowed for the formation of many different bond types, such as C–C, C–Cl, and C–S bonds.
Versatility and Broad Applicability
From these study findings, the xanthone photocatalyst proved to be highly applicable with more than 40 reaction examples. This large set of possible transformations highlights the power of the hydrogen atom transfer approach to carboxylic acid functionalization.
“I’m deeply honored to have collaborated with Associate Professor Hiroki Hayashi on this work,” Yamashita stated. “By integrating both experimental and computational approaches, we successfully revealed a novel photocatalysis of ketones. This project made me truly appreciate the power of the AFIR method in predicting reaction pathways. I hope our findings will open new avenues for controlling highly reactive radical species.”
The impacts of this research are far-reaching. It would have an enormous effect on pharmaceutical development and other industries that depend on organic synthesis. Developing the ability to produce carboxylic acids more selectively would represent a major breakthrough in producing new materials and compounds in just a few steps compared to hundreds.
Future Directions in Reaction Development
While their progress continues, the team is encouraged by the potential that computational methods will have on better informing the future of reaction development. Hayashi, who is looking for more progress in this area, said that the key will be developing new ways of thinking about chemical transformations.
The increased use of computational techniques as a complementary angle to experimental work is truly a paradigm shift in how researchers attack difficult and intricate chemical problems. By utilizing these artificial intelligence methodologies, chemists are able to better predict outcomes and cut steps out of a process, increasing efficiency in synthetic chemistry as a whole.
