59th Annual Report on Research 2014

(1)       Determining the Functional Group Tolerance of the Regioselective Semihydrogenation Methodology

(2)       Determining the Substrate Scope of the Regioselective Semihydrogenation Methodology (3)       Expanding the Methodology to Include Chemoselective Hydrogenolysis

(4)       Adapting the Methodology into a General Strategy for the Isomerization of Stilbenes

(5)       Expanding the Synthetic Potential of Ring-Closing Enyne Metathesis (RCEM)

During the first grant year of this project, we achieved Objectives 1 and 4, which resulted in two publications.  A summary of these accomplishments is provided in the first Narrative Report.  During this first award period, I was delighted to be awarded tenure and a full-year sabbatical, which I spent away from campus at Northwestern University and Merck Pharmaceuticals.  Accordingly, for reasons of safety and practicality, my undergraduate research lab was not in operation during the second academic year.  Upon my return that summer, we resumed work on proposal objective 2, and found a range of new substrates for which the regioselective hydrogenation was successful.  A summary of these accomplishments is provided in the preceding Narrative Report.  During the third and final grant year, we tackled objective 3, and the results are described below.  We were not able to attempt objective 5 during this grant period. 

Objective 3

Given that some functional groups are both stable to alkylboranes and susceptible to hydrogenolysis at atmospheric pressure and given the one-pot operational simplicity of the reaction sequence described above, this methodology could also be thought of as a strategy for the temporary protection of alkenes, especially terminal alkenes, against hydrogenolysis.  Accordingly, we designed syntheses of each of the following substrates and expect to produce the indicated products with our one-pot, three-step hydrogenation sequence.  These functional groups were chosen for initial investigations due to their expected operational simplicity, as they are expected to undergo hydrogenolysis at atmospheric hydrogen pressure and at room temperature.  The two students assigned to this project were new to a synthetic organic chemistry lab and spent the summer training in the techniques of synthesis.  They will continue work on this objective during this academic year.  We anticipate the results from this objective will be publishable in their own right but obtained outside of the timeframe of the grant.

Impact of the Work

Two of the six research papers that I have published in my independent career were directly funded by this grant, and I consider ACS-PRF funding to have been an essential component of both my successful tenure application and my successful application for a full-year, fully funded sabbatical.  Six undergraduates have been funded through this grant that would otherwise not have had an opportunity to do research in my lab.  One is now attending graduate school in organic chemistry at the University of Michigan and received an NSF pre-doctoral fellowship based on her work in my lab, and one is now in medical school at the University of Tennessee.  Two are seniors and are applying to graduate school, one in organic chemistry and one in chemical engineering.  Two are sophomores who continue to work in my lab with currently undecided career plans.