"From Moss to Microorganisms: Laboratory Reactive Intermediates in a Protein...within a Cell...for Artificial Biosynthesis"
Bio: John Hartwig currently holds the Dow Chair in Sustainable Chemistry after holding for 14 years the Henry Rapoport Chair in Organic Chemistry at the University of California, Berkeley. His research focuses on the discovery, development and mechanistic analysis of new reactions catalyzed by transition metal complexes, and he is well known for contributions to widely practiced cross-coupling chemistry that form aryl and allyl amines, ethers, sulfides, and carbonyl compounds, for hydroaminations of alkenes, for the discovery of practical C-H bond functionalization reactions of small molecules and of polyolefins and for creating artificial enzymes that enable laboratory chemistry to occur inside a protein, inside whole cells, and even inside biosynthetic pathways. On each of these topics, he has conducted detailed mechanistic analysis and revealed new elementary reactions of organotransition metal complexes.
For this work, he has received the Arthur C. Cope Award, the ACS award in Organometallic Chemistry, the H.C. Brown Award for Synthetic Methods, the Wolf Prize in Chemistry, and the BBVA Foundation Award in the Basic Sciences, among other recognitions. He was elected to the National Academy of Sciences in 2012 and the American Academy of Arts and Sciences in 2015. He is the author of the textbook "Organotransition Metal Chemistry: From Bonding to Catalysis."
Abstract: From my first paper in 1986 on the stereochemistry of dihalocarbene additions to cyclooctene, with Robert Moss as a coauthor, to some of our latest on reactions of carbenes in microorganisms, my group and I have been interested in controlling the selectivity of reactive intermediates. The introduction of functional groups at the positions of typically unreactive C-H bonds site-selectively and the stereo- and regio-selective functionalization of unconjugated C=C bonds have been longstanding challenges in catalysis, and to this end, our group has been motivated by the limits of small-molecule catalysts to create artificial metalloenzymes for such reactions. These artificial metalloenzymes contain synthetic cofactors possessing abiotic metal centers that catalyze unnatural reactions, particularly those of carbenes, with control over selectivity resulting from the protein environment. In the best-case scenario, such reactions occur within microorganisms and as part of an unnatural biosynthetic pathway to produce unnatural products.
This talk will include results from my group on new transformations, new mechanisms, new reactive intermediates, and new methods for in vivo assembly of artificial metalloenzymes. This combination of results has enabled us to combine an unnatural carbene-transfer reaction catalyzed by natural and artificial metalloenzymes with the biosynthesis of diazo compounds and natural reactions of a heterologous biosynthetic pathway. These advances enable the creation of engineered microorganisms that produce unnatural products by artificial biosynthesis encom- passing organometallic chemistry.