Mechanistic Role of Additives and Solvent in Sm(II)-Based Reactions

Lehigh University, Bethlehem PA

Investigators

Abstract

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.