Study of the ALDOL Reaction

Brown University, Providence RI

Investigators

Abstract

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.