PULLING TOGETHER

The field of organic synthesis has undergone a startling shift of emphasis during the past 20 years. The pinnacle of research was once the total synthesis of natural products. Many research groups fiercely competed to be the first to make a particular molecular target. Consequently, the field developed a highly competitive atmosphere, and it was rare to find synthetic organic chemists working together toward a common research goal.

Organic synthesis has now become much more diverse. The current focus is not so much on competition among chemists but on demonstrating the vital role that organic synthesis has on other established and emerging research disciplines. For instance, click chemistry and protein ligation are key in chemical biology, and metal-catalyzed cross-coupling is important to pharmaceutical and materials sciences.

One of the exciting developments for us is C–H functionalization. This synthetic methodology approaches the construction of organic molecules from a novel perspective. Rather than replacing or modifying reactive functional groups such as alcohols, amines, and carbonyls as was done in the past, chemists have learned how to modify typically unreactive C–H bonds, which are the most abundant functional groups in organic compounds. This strategy leaves the traditional functional groups alone and enables researchers to streamline the synthesis of new types of chemical entities, making reactions more sustainable and less expensive.

In 2008, we had the opportunity to initiate a new approach for organic synthesis collaboration, which eventually grew into the Center for Selective C–H Functionalization (CCHF), one of the National Science Foundation’s Centers for Chemical Innovation. We had just moved to Emory University and recognized that the rapid development of C–H functionalization would benefit from a broad-based approach involving many chemists and perspectives.

The ultimate goal of the center, which now has a team of 23 faculty members from 15 academic institutions across the U.S., is to further develop selective C–H functionalization so that it will continue to revolutionize the practice and reshape the teaching of chemical synthesis. More than half of CCHF’s faculty are synthetic organic chemists of various flavors involved in methodology development, total synthesis, and applications in the materials and pharmaceutical sciences. Recognizing that this focused expertise was not enough to effectively achieve our goals, we brought in experts from the fields of reaction optimization, chemical engineering, inorganic catalyst design, enzymology, and theoretical chemistry to complement the efforts of the synthetic chemists.

In addition, CCHF has several industrial partners participating in collaborative precompetitive research. Chemical companies, in particular in the pharmaceutical industry, have long forged collaborations with individual academic researchers. But the ability for academic and industrial chemists to work together more openly on basic synthetic strategies before patentable applications are developed is enhancing the translation of academic C–H functionalization research to the industrial setting.

The biggest challenge for CCHF has been to overcome the tight-lipped, head-down approach of organic chemists of the past. We needed to develop a new attitude toward collaboration, one that fosters an atmosphere in which ideas can be freely exchanged and considered while working toward a common set of goals.

Sharing one’s research ideas as they are hatched is always risky. When we started the center, none of the original members had collaborated, and in fact many people would have considered us research competitors rather than collaborators.

We began with a symposium in which all the professors and their students came together for brainstorming, not only on potential research projects, but also on what would be the best practices for effective collaboration. This is now a yearly event.

The center’s members are widely dispersed, so we needed to devise an efficient way for regular communication. This led us to the real backbone of CCHF’s efforts: weekly videoconferences during which 20 to 30 groups discuss their latest results and new research opportunities. We have become so adept at multisite communication that we have expanded our reach and created a global network involving universities in Japan, South Korea, and the U.K. This year we went a step further and began a virtual symposium on C–H functionalization, which was held on July 28. The symposium attracted more than 1,300 participants joining us from lecture halls at several pharmaceutical companies and about 70 universities around the world.