Topic: Translational Chemistry
Speaker: Phil S. Baran, Professor of Chemistry, The Scripps Research Institute
Abstract: There can be no more noble undertaking than the invention of medicines. Chemists that make up the engine of drug discovery are facing incredible pressure to do more with less in a highly restrictive and regulated process that is destined for failure more than 95% of the time. How can academic chemists working on natural products help these heroes of drug discovery – those in the pharmaceutical industry? With selected examples from our lab and others, this talk will focus on that question highlighting interesting findings in fundamental chemistry and new approaches to scalable chemical synthesis.
Biography: Phil Baran was born in 1977 in Denville, New Jersey. He received his B.S. in chemistry from NYU in 1997, his Ph.D. at The Scripps Research Institute in 2001, and from 2001-2003 he was an NIH-postdoctoral fellow at Harvard. His independent career began at Scripps in the summer of 2003. He currently holds the Darlene Shiley Chair in Chemistry. Phil has published over 180 scientific articles and has been the recipient of several ACS awards such as the Corey (2015), Pure Chemistry (2010), Fresenius (2006), and Nobel Laureate Signature (2003), and several international distinctions such as the Hirata Gold Medal and Mukaiyama Prize (Japan), the RSC award in Synthesis (UK), and the Sackler Prize (Israel). In 2013 he was named a MacArthur Foundation Fellow, in 2015 he was elected to the American Academy of Arts and Sciences, in 2016 he was awarded the Blavatnik National Award, and in 2017, he was elected to the National Academy of Sciences, USA. He has delivered hundreds of lectures around the world and consults for numerous companies such as Bristol-Myers Squibb (since late 2005), Boehringer-Ingelheim, AstraZeneca, DuPont and TEVA, and is a scientific advisory board member for Eisai, Abide, and AsymChem. In 2016 he was appointed as an Associate Editor for the Journal of the American Chemical Society. He co-founded Sirenas Marine Discovery (2012) and Vividion Therapeutics (2016) and in 2013 he co-authored The Portable Chemist’s Consultant, an interactive book published on the iBooks store along with his graduate class in Heterocyclic Chemistry (viewable for free by anyone on iTunes University). Outside of the lab, Phil enjoys spending time with his wife Ana and three young children (Lucia, Leah, and Manuel).
Topic: Enantioselective and Remote C–H Activation Reactions
Speaker: Jin-Quan Yu, Department of Chemistry, The Scripps Research Institute
Abstract: The vast majority of directed C–H activation reactions proceed via cyclometallation, in which a strongly coordinating functional group binds to the metal and facilitates cleavage of a proximate C–H bond. These substrates driven reactions become problematic backgroundreactions for developing enantioselective C–H activation reactions.The use of weak coordination from substrates to direct metal insertion opens the possibility of designing ligand to significantly accelerate C–H activation reactions. In ideal scenario of developing asymmetric C–H activation reactions, the reaction should only proceed when chiral ligands are present. We have recently discovered a number of ligand scaffolds that can enable C–H activation reactions of weakly coordinating substrates that are otherwise unreactive. Further development of chiral ligands have enabled the enantioselective C–H activation reactions of methylene C–H bonds for the first time. This effort has also led to the development of a biomimetic asymmetric transformation based on desymmetrization of a ubiquitous isopropyl group.
Inspired by how enzymes use directing effect to achieve remote selective C–H activation, we have developed several site-selective remote C–H activation reactions which are fundamentally distinct from the classic directed C–H activation via cyclometalation processes. We focused our design on recognition of distance and geometry as the simplest parameters to achieve site selectivity, which has allowed us to enantioselectively activate C–H bonds at remote sites that are previously not accessible. The combinationof remote directing effect and ligand acceleration is analogous to flying a kite in the wind.
Biography: Jin-Quan Yu was born and raised in a rather isolated mountain valley in Zhejiang Province (Southwest of Shanghai). He received his B.S. in Chemistry at East China Normal University, where he worked with Professor Li-Xin Dai and Professor Bi-Qi Wu as a visiting student at Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences in 1987. Following a one-year course study in Shanghai Institute of Organic Chemistry, he went to Guangzhou Institute of Chemistry, Chinese Academy of Sciences to study terpene chemistry and heterogeneous catalysis under the supervision of Professor Shu-De Xiao and obtained his master’s degree in 1990. He stayed on as a research associate for four years and went to Cambridge University for his doctoral studies under the supervision of Prof. J. B. Spencer, where he studied biosynthesis and the mechanistic details of the hydrometallation step in asymmetric hydrogenation. He was elected as a Junior Research Fellow of St John’s College, Cambridge University in 1998. From 2001-2002, Jin-Quan worked on Pd-catalyzed allylic oxidation as a postdoctoral fellow at the Harvard University in the laboratories of Professor E. J. Corey. He returned to Cambridge University in 2002 and was appointed as a University Royal Society Research Fellow in 2003 to start his independent research towards developing asymmetric C–H insertion reactions. In 2004, he moved to Brandeis University as an Assistant Professor of Chemistry. He joined The Scripps Research Institute as an Associate Professor in 2007 and became a full Professor in August 2010. He was appointed as the Frank and Bertha Hupp Professor of Chemistry at The Scripps Research Institute in 2012. He received the Mukaiyama Award in 2012, the Raymond and Beverly Sackler Prize in the Physical Sciences in 2013, the Elias J. Corey Award in 2014, the MacArthur Fellowship in 2016, and the Pedler Award in 2017.
Research in his group focuses on developing C–H activation reactions to provide new disconnections for asymmetric synthesis and catalytic processes. In the past 15 years, he has developed new ligands and strategies to achieve enantioselective and remote C–H activation reactions of synthetically relevant substrates (200 publications on C–H activation). C–H activation reactions developed in his laboratory have been used in pharma industry including BMS, Pfizer, Vertex, Novartis, AbbVie, GSK, Genentech, Boehringer Ingelheim, Amgen, Abide and Eisai. He also cofounded a drug discovery company, Vividion, to exploit the power of C–H activation technologies.