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Event
2019 Harry and Carol Mosher Award Dinner Meeting
Title:
Single Electron Processes Enabling Organic Synthesis
Guest Speaker and 2019 Mosher Award winner:
Hirschmann-Makineni Professor of Chemistry
University of Pennsylvania, Department of Chemistry
Abstract:
In traditional cross-coupling reactions, a three-step catalytic cycle mechanistically based on 2-electron processes is employed: oxidative addition of a halide at Pd or Ni, transmetalation of an organometallic nucleophile with the oxidative addition intermediate, and reductive elimination, which releases the coupled product and regenerates the Pd0 or Ni catalyst. Although such methods are highly effective for Csp2-Csp2 coupling, extension to 2 and 3 Csp3-hybridized organoboron reagents in particular has proven challenging owing primarily to lower rates of transmetalation, which is rate limiting in many alkylmetallic cross-coupling protocols operating under the traditional mechanistic manifold. To date, strategies aimed at facilitating the transmetalation of Csp3 cross-coupling reactions with functional group-tolerant organoboron or organosilicon reagents employ harsh reaction.
The limitations of the transmetalation in cross-coupling reactions are inherent to the mechanism of this process at the most fundamental level, and thus predispose many Csp3-hybridized alkylmetallic reagents for failure. Described is a novel, single electron mechanistic paradigm for cross-coupling that avoids this problem. Thus, dual catalytic cycles are established: a photoredox catalytic cycle, generating radicals from appropriate precursors, and a cross-coupling catalytic cycle that funnels these radicals into a base metal catalytic cycle that effects the cross-coupling. The nature of the cross-coupling cycle, in which high-energy radical intermediates engage the cross-coupling catalyst, insures a cascade of low energy events leading to product, avoiding the high energy of activation associated with previous cross-coupling protocols.
Described will be our efforts to develop a suite of radical precursors for cross-coupling with a variety of electrophiles, emphasizing the tolerability of the developed conditions to an unprecedented array of functional groups. The value of generating radicals in a process that is synchronized and catalytic will be emphasized, both in dual catalyzed processes and in radical/polar crossover processes where a subsequent catalytic transformation is not utilized. Finally, applications to DNA-encoded library synthesis will be presented.
Biography:
Professor Molander received his B.S. degree in chemistry from Iowa State University under the tutelage of Richard C. Larock and his Ph.D. with Herbert C. Brown at Purdue University. After a postdoctoral stint at the University of Wisconsin, Madison, with Barry M. Trost, he began his independent career as an assistant professor at the University of Colorado, Boulder, rising through the ranks to professor before moving to the University of Pennsylvania, where he served as Chair from 2009 to 2018. His research interests are in the development of new synthetic methods for organic synthesis, particularly in the invention of transition metal-catalyzed protocols for the construction of carbon-carbon bonds.
He has won numerous awards for his research, including the American Chemical Society Herbert C. Brown Award for Creative Research in Synthetic Methods. He currently serves in editorial roles at Organic Letters, Organic Reactions, and at Thieme with Science of Synthesis. He has been an active member of the Division of Organic Chemistry of the American Chemical Society, serving as Member-at-Large of the Executive Committee, Secretary-Treasurer, and Chair of the Division. He was also the Executive Officer of the National Organic Symposium, and currently serves as one of the co-chairs of the Division of Organic Chemistry Graduate Research Symposium, and was elected a Fellow of the American Chemical Society.
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LocationMacArthur Park-Julia Morgan Room (View)
27 University Ave
Palo Alto, CA 94301
United States
Categories
| Kid Friendly: No |
| Dog Friendly: No |
| Non-Smoking: Yes! |
| Wheelchair Accessible: Yes! |
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