Samarium diiodide (SmI2) and other Sm(II)-based reductants provide unique reagents for a variety of important synthetic transformations. One of the distinctive features of Sm(II)-based reductants is that their reactivity can be drastically altered by changing the solvent or by adding cosolvents or other additives. Although great strides have been achieved in the use of Sm(II) reagents in organic synthesis, the role of solvent and additives in reactions is poorly understood, and, as a result, the full potential of these reductant-additive combinations has not been realized. This work is directed towards understanding the relationship between solvent and additives and their effect on the rates and selectivities of Sm(II)-mediated functional group conversions through two discrete mechanistic studies. The first study will define the relationship between the affinity of solvents, proton donors, and coordinating or chelating additives for Sm(II) reagents and the relationship of these variables to the reactivity of Sm(II). This work will establish the degree to which coordinating solvents attenuate the reactivity of Sm(II) through interaction with substrates and commonly utilized additives providing chemists with important mechanistic data comparing the reactivity of Sm(II)-cosolvent complexes in a range of solvents in which they are commonly used. Overall, the goal of this portion of the work is to address the effects of solvation at the molecular level through the treatment of solvent as a high molarity ligand, not a medium of fixed dielectric constant. The second study addresses the mechanistic function of Ni diiodide and other transition metal salts on Sm(II)-mediated reductions. The impact of catalytic Ni diiodide and other Ni(II) salts on a range of reactions of SmI2 will be critically examined through a series of mechanistic studies employing stopped-flow spectrophotometry and reaction calorimetry. Mechanistic studies of reactions providing evidence for Ni(0)-based chemistry will be further investigated using reaction progress kinetic analysis. As these studies proceed, the intermediacy of Ni(0) nanoparticles will be examined to distinguish homogeneity from colloid-based chemistry. The broad goal of this work is designed to provide a mechanistic understanding of Sm(II)-based chemistry that can be extrapolated and applied to a range of important and useful processes. Studies utilizing this approach are likely to provide longer term benefits to the scientific community than simply the demonstration of a single synthetic application. The work contained in this proposal will also provide important professional preparation for graduate and undergraduate students in the mechanistic study, use, and applications of a reagent that is becoming increasingly important in organic synthesis. Students will receive training in the use and application of a range of useful techniques not typically used in standard organic laboratories and therefore the breadth of tools used in this project will provide unique training and perspective to organic students. Inclusion of undergraduate students from the Lehigh advanced laboratory course sequence in the mechanistic study and development of reactions employing the SmI2/catalytic Ni diiodide system will provide important training not typically acquired in a traditional undergraduate laboratory course.
Samarium diiodide (SmI2) is an important electron transfer reagent used by organic chemists to synthesize molecules of potential societal importance. Often times additives are employed to accelerate or alter the selectivity of reactions. In some cases, the additives employed are toxic, or their mechanism of action is not known or fully understood. The goals of this project were to understand how additives important in reactions of SmI2 enhance the reagents reactivity. Over the course of the work, two general types of additives were examined: 1) additives that coordinate to SmI2, and 2) transition metal salts added to reactions in catalytic amounts. Work carried out in the first portion of these studies showed that additives capable of displacing iodide from Sm while leaving open coordination sites for substrate provides a means to enhancing the reactivity of SmI2. This has been used to design alternative approaches to the reduction of cyclic lactones and ketone-alkene coupling reactions. Overall, these studies demonstrate that a range of additives can be used to accelerate reactions of SmI2 through displacement of iodide ligands. The key feature for successful implementation of this approach is the use of additives that have a high enough affinity for Sm(II) to displace iodide, yet do not fully saturate the coordination sphere inhibiting substrate reduction. Work in the second part of the project demonstrated that reactions using SmI2 and catalytic Ni(II) proceed through reduction of Ni(II) to Ni(0) in a rate-limiting step. Once formed, Ni(0) inserts into the alkyl halide bond through oxidative addition to produce an organonickel species. During the reaction, formation of colloidal Ni(0) occurs concomitantly with Ni(0) oxidative addition as an unproductive process. Overall, this study showed that a reaction thought to be driven by the unique features of SmI2 is a result of Ni(0) chemistry. An open acces video journal highlighting a portion of the work described above is available at: www.jove.com/video/4323/preparation-use-samarium-diiodide-smi2-organic-synthesis-mechanistic In addition to the scientific merits of the work, this project also provided important professional training to undergraduate and graduate students preparing them for careers in science, technology, and health. Some aspects of this work were also used in the development of a class for students considering a major in chemistry.
