Bergman Cyclization[Alaina Rumrill] Dr. Robert Bergman, a distinguished chemistry professor at UC Berkeley, is renowned for his pioneering work in organic synthesis, particularly for his groundbreaking discovery of Bergman cyclization. His journey into this area of research began during his postdoctoral studies at Columbia University, where he worked under the mentorship of renowned chemist Ronald Breslow [1]. During this time, Dr. Bergman developed a deep interest in aromaticity, specifically in non-benzonoid aromaticity, which involves creating compounds that exhibit stability similar to benzene but with a different structural framework [1]. The Bergman cyclization is a remarkable chemical reaction that involves the transformation of an enediyne precursor into a highly reactive intermediate known as dehydrobenzene (C₆H₄) [2]. Dehydrobenzene is a molecule that had long been theorized but was extremely challenging to synthesize due to its instability and the difficulty of controlling its formation [1]. Dr. Bergman, along with his graduate student Richard Jones, undertook the task of synthesizing this elusive intermediate. They discovered that by heating the enediyne compound to the appropriate temperature, the molecule would undergo cyclization, forming dehydrobenzene as an intermediate [1]. This process was groundbreaking because it required no catalysts or additional reagents, relying solely on thermal energy to drive the reaction forward.Figure 1. Reversible Bergman CyclizationAt the time of its discovery, Dr. Bergman did not foresee the significant biological relevance that his research would later uncover. However, the reaction’s ability to generate a highly reactive diradical species, capable of abstracting hydrogen atoms from the DNA backbone, opened new avenues in the study of DNA cleavage [1]. This discovery became particularly important in the development of anti-cancer therapies. Researchers at Bristol-Myers Squibb, built upon Bergman’s findings to explore the potential of enediyne compounds as anti-cancer agents [1]. These compounds were found to induce DNA damage selectively in cancer cells, leading to the development of targeted therapies that could potentially minimize harm to healthy cells [1].CH Bond FunctionalizationDr. Robert Bergman’s work on carbon-hydrogen (CH) bonds represents a significant milestone in organic chemistry, particularly in the field of CH bond functionalization. CH bonds are among the most common and fundamental bonds in organic molecules, forming the backbone of countless compounds that are essential to life [1]. CH bonds are notoriously difficult to break due to their strong covalent nature, which has traditionally required high temperatures or the generation of highly energetic intermediates to overcome their stability [1]. This challenge has long been a barrier to advancing organic synthesis and developing new methods for constructing complex molecules.Dr. Bergman’s research addressed this challenge by focusing on the activation of CH bonds in hydrocarbons—a category of organic molecules that includes compounds like ethane, butane, and propane [1]. These simple hydrocarbons are abundant in nature and are critical components of many industrial processes, however, their inertness has made them difficult to modify selectively [1]. The key to Bergman’s breakthrough lay in his innovative use of metal catalysts, which, when exposed to ultraviolet light, generated a highly reactive metal center capable of breaking CH bonds in hydrocarbons [1]. He discovered that metal catalysts could interact with and break CH bonds in hydrocarbons under milder conditions than previously thought possible.The process of CH bond functionalization involves several key steps. First, a metal catalyst interacts with the CH bond, facilitating the formation of a new metal-carbon bond. This interaction weakens the CH bond, leading to the release of hydrogen and the formation of a reactive intermediate [1]. The final step replaces the broken CH bond with a new bond, effectively functionalizing the molecule. This transformation opens up a range of possibilities for organic synthesis, allowing chemists to introduce new functional groups into hydrocarbons and create more complex and useful molecules [1].The implications of Dr. Bergman’s work on CH bond functionalization are vast. By enabling the selective modification of unactivated CH bonds, Dr. Bergman has paved the way for more efficient and sustainable chemical processes. In drug design and delivery, the ability to functionalize CH bonds can lead to the development of new pharmaceuticals with improved efficacy and reduced side effects [1]. Additionally, this method offers new strategies for creating more environmentally friendly chemicals and materials, reducing the need for harsh reaction conditions and toxic reagents [1].Inspiring StudentsDr. Robert Bergman’s influence extends beyond his groundbreaking work in organic chemistry into the realm of education. Recognizing the critical need for early science education, Dr. Bergman helped establish the Bay Area Scientists Inspiring Students (BASIS) program in the late 1990s [1]. This initiative began as a response to concerns about the limited focus on science in elementary education. By rallying volunteers from UC Berkeley’s chemistry department, Dr. Bergman created a platform for scientists to engage directly with elementary students, conducting hands-on science demonstrations [1].Today, BASIS includes over 700 volunteers and has grown to serve a wide array of schools across the Bay Area. It includes contributions from students and professionals across various UC Berkeley departments and industrial partners. The program’s expansion has reached numerous communities, including San Francisco, the East Bay, Oakland, Richmond, Emeryville, and Pinnel [1]. BASIS aims to spark a lasting interest in science, break stereotypes about scientists, and provide young students with memorable, hands-on experiences. By involving female and minority scientists, it challenges traditional stereotypes and encourages a diverse range of students to envision themselves in scientific careers. Through BASIS and other efforts, Dr. Bergman has not only advanced scientific knowledge but has nurtured the curiosity and potential of future generations.Learn MoreIf you’d like to hear more about Dr. Robert Bergman’s journey in chemistry and his work in organic synthesis, visit us on Spotify, Apple Podcasts, and many other streaming services to listen to our ChemTalk Podcast with Dr. Robert Bergman, the Gerald E.K. Branch Distinguished Professor of Chemistry at UC Berkeley with an Emeritus status. Find the ChemTalk podcast here.Works Cited[1] Bergman, Robert. Personal interview. Conducted by Olivia Lambertson and Jasmine Winter. 11 October 2023.[2] “Bergman Cyclization Bergman Cycloaromatization.” Organic Chemistry. Accessed August 11, 2024. https://www.organic-chemistry.org/namedreactions/bergman-cyclization.shtm .
