Lewis-base Activation of Lewis Acids:
An Evolving Paradigm for
Catalysis in Main Group
Catalysis is a chemical evergreen. Ever since Michael Faraday first recognized that platinum wire could bring about the combination of hydrogen and oxygen with spectacular speed, chemists have been fascinated with the origins, principles, scope and applications of catalysis. Despite Berzelius’s unfortunate choice of the word for this phenomenon (from the ancient Greek for destruction), the field of chemical (abiological) catalysis has grown immensely in the past century. Surprisingly however, catalysis of reactions of the p-block (main group) elements is almost non-existent. Over the past decade, this group has investigated reactions based on elements in Groups 13, 14, 16 and 17, under the newly developed paradigm of “Lewis-base activation of Lewis acids.” This lecture will describe the most recent efforts in our laboratories to design, understand and apply synthetically useful reactions of, inter alia, the halogens and the chalcogens under catalysis by Lewis bases.
These reagents are particularly useful for the vicinal functionalization of alkenes initiated by chalcogens and halogens with capture of the putative -iranium ions by various nucleophiles both inter- and intramolecularly with oxygen, nitrogen and carbon-based nucleophiles. The ability of various Lewis basic moieties to activate the electrophilic functionalization of double bonds has been demonstrated for S, Se, Cl, Br and I. Extensive mechanistic investigations have established the intermediacy and configurational stability of thiiranium and seleniranium ions as well the corresponding haliranium ions. These studies have led to the development of catalytic enantioselective chalcogenoand halofunctionalization reactions. Most recently, the use of enantioselective sulfenofunctionalization has enabled highly selective polyene cyclizations and 1,2-metalate rearrangements. All of these methods have been investigated mechanistically to elucidate the origins or reactivity and selectivity through kinetic, spectroscopic, crystallographic and computational analysis.
Professor Scott E. Denmark,
Department of Chemistry
University of Illinois at Urbana-Champaign
Scott E. Denmark is the Reynold C. Fuson Professor of Chemistry at the University of Illinois at Urbana-Champaign. He obtained an SB degree from M.I.T. in 1975 and did his graduate studies at the ETH-Zürich under the direction of Professor Albert Eschenmoser, culminating in a DSc Tech degree in 1980. That same year he began his career as assistant professor at the University of Illinois. He was promoted to associate professor in 1986, full professor in 1987 and then in 1991, named the Reynold C. Fuson Professor of Chemistry.
Denmark is primarily interested in the invention of new synthetic reactions and elucidating the origins of stereocontrol in novel, asymmetric reactions. The current emphasis in his laboratories focuses on the relationship between structure, reactivity and stereoselectivity in a variety of organoelement processes. He has pioneered the concept of chiral Lewis-base activation of Lewis acids for catalysis in main group synthetic organic chemistry. His group has also developed palladium-catalyzed crosscouplings with organofunctional silicon compounds. In addition, his research program encompasses the development and application of tandem heterodiene cycloadditions for the synthesis of complex natural (alkaloids) and unnatural (fenestranes, phase transfer catalysts) nitrogen containing compounds. In recent years his group has investigated the use of chemoinformatics and machine learning to identify and optimize catalysts for a variety of organic and organometallic reactions. Denmark has won a number of honors for both research and teaching. These include: A. P. Sloan Foundation Fellowship, NSF Presidential Young Investigator Award, A. C. Cope Scholar Award (ACS), Alexander Von Humboldt Senior Scientist Award, Pedler Lecture and Medal (RSC), the ACS Award for Creative Work in Synthetic Organic Chemistry, the Yamada-Koga Prize, the Prelog Medal (ETH-Zürich), the H. C. Brown Award for Creative Research in Synthetic Methods (ACS), Robert Robinson Lecture and Medal (RSC), the ISHC Senior Award in Heterocyclic Chemistry, Paul Karrer Lectureship (Uni Zürich), the Frederic Stanley Kipping Award for Research in Silicon Chemistry (ACS), and the Harry and Carol Mosher Award (Santa Clara Section, ACS). He is a Fellow of the Royal Society of Chemistry and the American Chemical Society.
In 2017, Denmark was elected to membership in the American Academy of Arts and Sciences and in 2018, he became a member of the National Academy of Sciences. He has received numerous honorary lectureships and visiting professorships and has served on many editorial advisory boards. He edited Volume 85 of Organic Syntheses, was editor of Volumes 22-25 of Topics in Stereochemistry and was a founding associate editor of Organic Letters (1999–2004). After serving on the editorial board from 1994–2003, he became editor in chief and president of Organic Reactions, Inc. in 2008.
Professor John J. Eisch
John Joseph Eisch joined the Department of Chemistry at Binghamton University in 1972, as chair and professor of chemistry, with the mandate of fostering the national reputation of its graduate teaching and research. Over the next six years as chair, he guided the recruiting of six senior and junior faculty with this goal in mind, while expanding his own research in organometallic chemistry to a yearly group of eight to 12 graduate and postdoctoral students, with support from federal and industrial resources. In 1983, his composite achievements were recognized by his promotion to the SUNY-wide rank of distinguished professor of chemistry. Further recruiting, notably during the chair tenure of professors Eugene Stevens, Alistair Lees, Wayne Jones and currently, Eriks Rozners, expanded the scope of advanced research into areas of immediate importance, such as nano materials, homogeneous catalysis, analytical sensors, biological transformations and energy storage.
Eisch received the BS degree in chemistry, summa cum laude, from Marquette University in 1952; earned the PhD degree in 1956, with Henry Gilman, at Iowa State University; and served as Union Carbide Research Fellow with Karl Ziegler at the Max-Planck-Institut für Kohlenforschung, Mülheim, Germany (1956–57). After junior professional appointments at St. Louis University and the University of Michigan, he became ordinary professor and department head at the Catholic University of America (1963–1972). He retired from his professorial career of 57 years in 2014, the latter 42 years of which were spent at Binghamton University.
The Eisch Group initially had concentrated on the preparation and organic synthetic uses of organometallic reagents of Li, Na, Mg, B and Al, but we were struck by the lack of definitive molecular mechanistic studies in previous work. In ensuing research encompassing reaction kinetics, trapping of any intermediates, IR, UV and X-ray crystallographic measurements, both heterolytic and homolytic C-M cleavages could be involved, as well as 4-centertrapesoidal transition states. Reviews are available in a) “Fifty Years of Ziegler- Natta Polymerization: From Serendipity to Science,” Organometallics, 2012, 31, 4917–4932 and b) Dalton Transactions, (DOI: 10:1039/c4dt010362) “Emergence of Electrophilic Alumination as the Counterpart of Established Nucleophilic Lithiation.” The original seven articles dealing with the reactions of RLi with the azomethyne groups have been recently published by the Eisch and the Rheingold Crystallographic Group in the European Journal of Organic Chemistry.
Over the years, the research involved the fruitful collaboration of more than 200 students as master’s, doctoral, postdoctoral or baccalaureate associates. The results have been reported in more than 410 scientific publications, in some 280 invited lectures worldwide, in the monograph “The Chemistry of Organometallic Compounds” (Macmillian, 1967) and in the edited series, “Organometallic Syntheses” (four volumes, J. J. Eisch and R. B. King, authors and editors). He has been an industrial consultant on organometallic chemistry and an expert witness in several patent litigations on Ziegler-Natta polymerization catalysis.
Previous Lectureship Recipients
Stephen L. Buchwald
“Palladium-Catalyzed CarbonNitrogen and Carbon-Carbon Bond-Forming Reactions: Progress, Applications and Mechanistic Studies”
David W. C. MacMillan
“The Use of Photoredox Catalysis in New Organic Bond Forming Reactions”
Brian M. Stoltz
California Institute of Technology
“Complex Natural Products as a Driving Force for Discovery in Organic Chemistry”
Eric N. Jacobsen
“Organometallic Catalysis for Solar Fuels and Storage”
Phil S. Baran
The Scripps Research Institute
Stephen J. Lippard
“Understanding and Improving Platinum Anticancer Drugs”
Daniel A. Singleton
Texas A&M Uniersity
“Dynamic Effects and Energy Labeling in Free-Radical Reactions”
Clifford P. Kubiak
University of California, San Diego
“Dynamic Effects and Energy Labeling in Free-Radical Reactions”