Maria C. Milletti, PhD, Eastern Michigan University
The goal of this funded research project is to investigate the stereospecific synthesis of substituted pyrrolidines from a computational perspective in order to inform and guide the choice of experimental conditions leading to maximum stereoselectivity. The synthetic pathway under consideration is the tandem aza-Cope – Mannich reaction, an efficient method to the formation of a variety of substituted pyrrolidines that can serve as asymmetric organocatalysts.
During this first year of the grant we have explored
We investigated these key aspects of the synthesis by considering how the choice of Lewis acid and oxazolidine substituents alters our conclusions. Specifically, we have used three iminium cation substituents with varying steric and electronic characteristics, as well as comparing more- or less-heavily substituted carbonyl groups in the pyrrolidine product.
Results obtained to date are as follows:
During the second year of the grant, we plan to continue our investigation of the effect of substituents’ steric and electronic characteristics on the energy profile of the aza-Cope – Mannich reaction and product distribution of stereoisomers.
In addition, we will model the reaction using chiral Lewis acids to see if they impart a particular conformation to key intermediates.
This project is in collaboration with one of my colleagues at Eastern Michigan University, Prof. Harriet Lindsay, who is carrying out the experimental work. The grant has allowed me to make significant progress on the project by giving me the opportunity to hire student researchers. Prof. Lindsay and I believe that by next summer we will have enough data to submit a grant proposal to NSF to secure continued funding for this joint project.
In addition, financial support from this grant provided my students with the opportunity to present their results at the ACS Central Regional meeting in May of this year and at the ACS Fall National Meeting in August. This was a tremendous opportunity for them, as this was the first time they had presented their work to other chemists. Participation at both events gave them confidence in their abilities to do research at a professional level and they have begun to consider graduate school as an option after graduation.
Attendance at the ACS National meeting also gave them an opportunity to hear about areas of chemistry other than our own computational field. They talked to recruiters from several companies and one of them is going to pursue an internship with NASA next summer.
The increased activity in my lab has also been an excellent recruiting tool and two new students joined our research group this fall. I am sure that this academic year will be a very productive one.