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

二碘化钐(SmI2)和其他基于Sm(II)的还原剂为各种重要的合成转化提供了独特的试剂。基于Sm(II)的还原剂的一个显著特点是，通过改变溶剂或添加助溶剂或其他添加剂，可以极大地改变其反应活性。尽管Sm(II)试剂在有机合成中的应用取得了长足的进步，但人们对溶剂和添加剂在反应中的作用知之甚少，因此，这些还原剂-添加剂组合的潜力还没有充分发挥出来。这项工作旨在通过两个离散的机理研究来了解溶剂和添加剂之间的关系以及它们对Sm(II)介导的官能团转化的速率和选择性的影响。第一个研究将确定溶剂、质子给体和配位或螯合添加剂对Sm(II)试剂的亲和力之间的关系，以及这些变量与Sm(II)反应活性的关系。这项工作将确定配位溶剂通过与底物和常用添加剂的相互作用减弱Sm(II)的反应性的程度，为化学家提供重要的机理数据，比较Sm(II)-助溶剂络合物在一系列常用溶剂中的反应活性。总体而言，这部分工作的目标是通过将溶剂作为高摩尔配基而不是固定介电常数的介质来处理分子水平上的溶剂化效应。第二个研究探讨了二碘化镍和其他过渡金属盐对Sm(II)介导的还原的机理作用。催化二碘化镍和其他镍(II)盐对SmI2一系列反应的影响将通过停流分光光度法和反应量热法进行一系列机理研究。为Ni(0)基化学提供证据的反应机理研究将利用反应进度动力学分析进行进一步研究。随着这些研究的进行，将检查Ni(0)纳米颗粒的中间体，以区分均质和胶体化学。这项工作的广泛目标是提供对Sm(II)基化学的机械理解，这种理解可以外推并应用于一系列重要和有用的过程。使用这种方法的研究可能会给科学界带来更长期的好处，而不是简单地展示单一的合成应用。这项提案中包含的工作还将为研究生和本科生在有机合成中日益重要的试剂的机械学习、使用和应用方面提供重要的专业准备。学生将接受使用和应用一系列有用技术的培训，这些技术通常不是标准有机实验室中使用的，因此，该项目使用的工具的广度将为有机学生提供独特的培训和视角。将LeHigh高级实验室课程序列的本科生纳入使用SmI2/催化二碘化镍体系的反应的机理研究和开发中，将提供传统本科实验室课程通常不具备的重要培训。

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.