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We made excellent progress towards our stated project goals, and our current objectives have not deviated significantly from those outlined in the original proposal. We did not make 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 for their desired substrate. In every case the desired substrate has never been synthesized before. To date, five of the six students listed on this and the previous report have successfully synthesized their desired substrate. All but one chose to continue work on their project during the subsequent academic term as part of our Independent Research course CHM-075.

Of the five students who have synthesized their desired substrate, two are actively investigating their respective key reaction as described in the proposal. To date, none of these reactions have been successful, although it is still 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 transformation. Three students have exhaustively tested their key reaction with no success, and we have abandoned those sub-projects. Though these particular results are disappointing. I remain confident that in time we will discover that one of the proposed or related reactions is successful.

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, both 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.

The student working on this first sub-project (Charles Reese) has repeated the literature precedent and has, over the course of this past summer, prepared every substrate necessary to conduct the study outlined in the preceding paragraph. Though I regret not having the study, and the expected associated paper, completed before the conclusion of this grant, the reagents and equipment purchased with these grant monies will allow us to complete the study over the course of the coming year without need for any additional funds.

The student who was funded by this grant over the summer (Mac Felmly) continues to work in my lab this term as well. He is investigating the reactivity of a more reactive difluorinated cyclopropane analog in place of an unsubstituted cyclopropane for one the failed reactions described above. We have initial results that, unlike unsubstituted cyclopropanes, these difluorocyclopropanes are quite reactive under our reaction conditions, and Mac is currently analyzing reaction products to determine if the desired transformation indeed occurred.

Though out investigations are ongoing, one measurable result of the impact of this project on the scientific enterprise is the number of students who have worked on this project that are either in, applying to, or planning to apply to graduate school. Over the past three years, ten students have trained on this project. Of the ten, four are in graduate schools studying organic chemistry (Indiana, Irvine, Vanderbilt, and Princeton), three are planning to apply to graduate school, one is teaching high school chemistry, one is in the seminary, and one is in the Peace Corps. This project, and the essential funding provided by ACS-PRF to carry it out, has been instrumental in the training of many future organic chemists.