Research in the Ritter group focuses on the development of novel reaction chemistry. We seek to discover molecular structure and reactivity that can contribute to interdisciplinary solutions for challenges in science. The lab focuses on synthetic organic and organometallic chemistry, complex molecule synthesis, and mechanistic studies to develop practical access to molecules of interest in catalysis, medicine, and materials.
“Carbon–Fluorine Reductive Elimination from a High-Valent Palladium Fluoride” J. Am. Chem. Soc. 2008, 130, 10060–10061
“Bimetallic Pd(III) complexes in palladium-catalysed carbon–heteroatom bond formation” Nature Chem. 2009, 1, 302–309
“Silver-Catalyzed Late-Stage Fluorination” J. Am. Chem. Soc. 2010, 132, 12150–12154
“A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging” Science 2011, 334, 639–642
|Functional Group-Tolerant Late-Stage Carbon–Fluorine Bond Formation
Many of the most useful synthetic molecules, including numerous pharmaceuticals, contain fluorine due to the desirable unique properties of fluorinated molecules. Carbon–fluorine bond formation is a challenging chemical transformation, especially in the context of general, functional group-tolerant late-stage fluorination of arenes. Our approach to carbon–fluorine bond formation is based on the use of high-valent transition metal fluorides via oxidation of aryl transition metal complexes with electrophilic fluorination reagents. A long-term goal of our research is the development of new methods for the synthesis of small-molecule tracers for positron emission tomography (PET), a powerful imaging technique to study biological processes in vivo. The conceptual advance of our approach is the implementation of new organometallic, organic, and inorganic chemical reactivity as solutions to challenges of interest to the biomedical community. Ultimately, we envision engaging in translational research through new and existing collaborations with physicians and imaging experts to affect the broadest possible impact of our science.
|Figure 1: (Top) Late-stage fluorination of complex small molecules. (Bottom) Late-stage fluorination for the general synthesis of previously unavailable PET tracers. A general, late-stage fluorination reaction may have a profound impact on molecular PET imaging.|
|Carbon–fluorine bond formation via reductive elimination is a rare process. We have reported the first isolation of a high-valent palladium fluoride, which can undergo carbon–fluorine reductive elimination. Our work describes the first reductive elimination of an aryl fluoride from a transition metal complex. We identified that C–F reductive elimination proceeds efficiently from aryl Pd(IV) fluoride complexes, stabilized by pyridyl-sulfonamide ancillary ligands. We propose that the pyridyl-sulfonamide ligand plays a crucial role for facile and efficient C–F bond formation.|
|Figure 2: First structure of a high-valent Pd fluoride complex (1), first reductive elimination of a C–F bond to form an aryl fluoride from a transition metal complex.|
Bimetallic catalysis is employed by Nature for challenging transformations, such as selective oxidation of C–H bonds. Our group has discovered dinuclear Pd(III) complexes relevant to catalysis. Prior to our studies, the potential role of Pd(III) in catalysis had not been investigated because no organometallic reactions from Pd(III) had been reported. Our discovery has raised fundamental questions about redox catalysis by multinuclear complexes. We have probed and investigated the extent to which two metals cooperate synergistically during catalysis and are currently investigating the use of new bimetallic catalyst for the discovery of new reactions, such as oxidation reactions with O2.
|Figure 3: Proposed bimetallic catalyst cycle for oxidative Pd chemistry; well defined reductive elimination from dinuclear Pd(III)–Pd(III) complex (3); X-ray structure of dinuclear Pd(III)–Pd(III) intermediate (4).|
|As part of our program in redox catalysis, we have developed several iron-catalyzed addition reactions such as a chemo-, regio, and stereoselective 1,4-hydroboration of 1,3-dienes. Iron is environmentally benign and can adopt formal oxidation states ranging from – II to +VI, which makes it an ideal catalyst for the development of sustainable redox catalysis. Our goal is to develop valuable building blocks for organic synthesis from staple commodity chemicals. Toward this goal we envision practical catalysis being realized through rational design of well-defined iron complexes.|
|Figure 4: Use of well-defined iron complexes as catalysts for the 1,4-hydroalkenylation and 1,4-hydroboration of 1,3-dienes.|