47106-GB1
Development of Homologated [2,3] and [3,3] Sigmatropic Rearrangements
We have made excellent progress towards our stated project goals, and our current objectives have not deviated significantly from those outlined in the original proposal. We are not contemplating any significant changes to the original plan. Each new student who chooses to work on this methodology project is assigned their own synthetic route (four examples of which are described in the proposal). Thus, students are working independently on a sub-project and collaboratively on the overall project. After demonstrating to me their mastery of the scientific rationale for their project, usually obtained through literature readings and preliminary conversations, I ask students to reproduce in the laboratory the known chemical reactions on which their sub-project is based. This provides each student with practice in the techniques of modern organic synthesis and a clearly-defined and obtainable initial goal . To date, all but one listed on this report has successfully reproduced the known chemical reactions on which their sub-project is based. This also serves as an indication to me that they are intellectually and technically prepared to conduct independent research on a synthesis problem with no known solution. At this point, each student works with me to design a synthesis route to their desired substrate. In every case the desired substrate has never been synthesized before. To date, four of the five students listed on this report have successfully synthesized their desired substrate. All have chosen to continue work on their project during the fall academic term. Of the four students who have synthesized their desired substrate, three are actively investigating their respective key reaction as described in the proposal. To date, none of these reactions have been successful, although it is early in the reaction development process. I anticipate they will spend the remainder of this term working on variations in the reaction conditions in hopes of achieving the desired chemical transformation. The fourth student exhaustively tested her key reaction with no success, and we have abandoned that sub-project. She has since graduated. Based on our accumulated experience in this project, we have been able to make some generalizations that have aided us in identifying additional sub-projects that we feel have an enhanced likelihood of success. Indeed, two of my current students are working on sub-projects that were not conceived of at the time of proposal submission. One of these projects is essentially a reactivity study. Since this study was not described in the original proposal, I will outline its objectives here. The rearrangement of methylcyclopropane radicals and anions has been utilized for over 60 years. Recently, Movassaghi et al. has reported a new method for generating radicals and allyl anions from the decomposition of tosylhydrazone derivatives. This new reaction offers us the opportunity to investigate whether the analogous cyclopropyl homologs react as cycloproplymethyl radicals or as cyclopropylmethyl anions (or both) when present in a reaction that makes both possibilities accessible. The results of this study will provide additional insights into the nature of fundamental cyclopropane reactivity and, I expect, will be of interest to the synthesis community. After determining the outcome of the study in the lab, I anticipate collaborating with a computational chemist to acquire the corresponding in silico data and comparing the predictions one would make based on the computer-generated data to our laboratory results. This project will make for a nice stand-alone communication, and ACS-PRF will be acknowledged for its funding support.
