Study of the ALDOL Reaction

碱金属(Li、Na、K、Cs)和极少数阳离子(B、锌、钛)稳定试剂是有机合成中应用最广泛的有机金属试剂。然而，关于它们的溶液、固态结构和它们的反应，还有许多问题没有得到回答。对聚集态、配位数、配位配体的几何构型和密切的结构特征的更好的了解，已经开始为预测利用这些试剂的反应的立体选择性提供了一个更全面的模型。威廉教授提出了一项研究计划，旨在通过对许多常用的碳离子试剂进行衍射分析来获得结构信息。具体到这一提议是对Aldol反应的关注。长期目标是将获得的结构信息与更连贯的模型模式相适应，用于控制和预测机制和立体选择性。控制有机合成中的立体选择性对新试剂的设计尤为重要。重点将放在高活性和合成上重要的碳离子中间体的固态结构研究上。这个项目将针对特定的活性中间体，这是我们几乎所有合成机理模型的基础。一个著名的例子是经常被引用的烯/羟醛反应的Zimmerman-Traxler过渡态模型。尽管这种特殊的结构模型被成功地应用于许多烯醇反应的立体选择性的关联，但几乎没有实验证据来证明该模型的有效性。因此，这个项目的一个主要目标是提供结构信息和具体的机制细节，这些信息可以直接与已建立的模型相关，例如流行的齐默尔曼-特拉克斯勒模型。有了这个奖，有机和高分子化学计划支持布朗大学的保罗·G·威廉教授的研究。威廉教授是一位领先的X射线结晶学家和有机化学家，他感兴趣的是利用Aldol化学将烯醇盐的结构与其反应活性联系起来，这是有机合成中碳-碳键形成的关键。他的工作将包括本科生作为研究人员，其结果将对化学制造行业具有重要的实践意义。

Alkali metal (Li, Na, K and Cs) and a very few additional cationic (B, Zn, and Ti) stabilized reagents are among the most widely utilized organometallic reagents in organic synthesis. However, many questions remain unanswered concerning their solution and solid-state structures and their reactions. A better understanding of the aggregation state, the coordination number, the geometry of the attached ligands, and the intimate structural features have begun to provide a more thorough model for use in predicting the stereoselectivity in reactions utilizing these reagents. Professor Williard proposes a research program designed to obtain structural information by diffraction analyses for many commonly utilized carbanionic reagents. Specific to this proposal is a focus on the Aldol reaction. The long-range goal is to fit the structural information that is obtained into a more coherent pattern of models utilized to control and to predict mechanism and stereoselectivity. Controlling stereoselectivity in organic synthesis is especially important to the design of new reagents. An emphasis will be placed on the solid-state structural studies of highly reactive and synthetically important carbanionic intermediates. This project will target specific reactive intermediates, which are the basis of almost all of our synthetic mechanistic models. A well-known example is the often-cited Zimmerman-Traxler transition state model for enolate/aldol reactions. Although this particular structural model is applied with reasonable success to the correlation of stereoselectivity of many enolate reactions, very little experimental evidence exists to establish the validity of this model. Hence, a major goal of this project is to provide structural information and specific mechanistic details that can be directly related to established models such as the popular Zimmerman-Traxler model.With this Award, the Organic and Macromolecular Chemistry Program supports the research of Professor Paul G. Williard of Brown University. Professor Williard is a leading x-ray crystallographer and an organic chemist who is interested in correlating the structure of enolate salts with their reactivity using aldol chemistry, which is the key to carbon-carbon bond formation in organic synthesis. His work will involve undergraduate students as researchers and the results will be of significant practical importance to the chemical manufacturing industry.