59th Annual Report on Research 2014

  Background   There have been a few studies of the catalytic activities of substituted (cyclopentadienone)iron tricarbonyl compounds as alcohol oxidation and carbonyl reduction catalysts.  A vast majority of the iron compounds studied contained cyclopentadienones that were part of fused ring systems (such as those found in 1, 2, and 3).  During our initial exploration of tricarbonyl compound 1 we examined the reactivity of a few derivatives of 1.  We found that the cyclopentadienone substitution had a large impact on the catalyst’s activity, and others have come to similar conclusions.   A goal of our research is to synthesize a series of (cyclopentadienone)iron tricarbonyl compounds with systematic variations in the cyclopentadienone substitution and test these compounds to determine their catalytic activities.  Our hope is to discover a structure/activity relationship and to use it to develop more active catalysts.  At this point we have synthesized the compounds shown in Figure 1.  Many of these compounds are known and some of them have been used as oxidation or reduction catalysts.  As noted above, a majority of those that have been used as catalysts contain fused rings (1, 4, 5, 13–16).  

  To search for reactivity patterns based on cyclopentadienone substitution, each catalyst in Figure 1 has been/will be used in each of the six oxidation or reduction reactions shown in Scheme 2. Each reaction was chosen for a reason: reactions 1 and 3 are benzylic and aliphatic alcohol oxidations, respectively; reactions 2 and 4 are reduction reactions with varying steric hindrance; reaction 5 is a challenging substrate for these catalysts (presumably due to coordination of the nitrile to the iron center); and reaction 6 is an imine reduction.  

  Results from Year 2   Prior to the start of the grant and during the first funding period, we synthesized compounds 1 and 4–12 and began the process of testing them as catalysts in the six reactions shown in Scheme 2.  During this second cycle, we synthesized compounds 13–16 and focused our efforts on exploring catalyst reactivity through the lens of the six screening reactions. We optimized the process by which we analyze the reaction outcomes, and we modified catalyst loadings for each reaction to discover a loading that illustrates the differences in reactivity among catalysts. Currently we examine catalyst reactivity by performing each reaction with each catalyst at least three times, and the yields and conversions are determined by analysis of the reaction mixture by GC.    Because the catalytic activity of iron compounds bearing cyclopentadienones without fused rings has not been extensively explored, we initially focused on testing compounds 6–12 in our six oxidation and reduction reactions. Knölker’s compound 1 has been used extensively in these types of reactions, so we were interested in comparing its reactivity to those of 6–12.  After running the reactions, we were surprised to find that GC yields of reactions 1–6 run with compound 1 were reliably lower than those run with catalysts 6, 7, 9, 10, and 12.  For example, the average GC yield for the reduction of benzylideneaniline (reaction 6) with 1 is 27%, but it is 99% with catalysts 6 and 7.  We noticed early on that reactions catalyzed by 11 did not afford much product, so it was not tested as extensively as the others. When comparing reactions catalyzed by 6, 7, 9, 10, 11, and 12 there is not a clearly superior catalyst but catalyst 6 generally is near the top of the pack.  Dimethyl and diethyl compounds 6 and 7 lead to high GC yields in the acetophenone reduction (reaction 2) and benzylideneaniline reduction (reaction 6) reactions.  In alcohol oxidations (reactions 1 and 3) catalysts 6, 10, and 12 stood out as generating products in high yield.  As mentioned above, 4-cyanobenzaldehyde reduction (reaction 5) is challenging for these catalysts and yields typically top out at 15–30%.  While unsymmetrical compound 9 led to higher yields than 1, it was inferior compared to the others.   Looking forward, we are interested in seeing how substitution at the 3- and 4-positions of the cyclopentadienone impact catalyst reactivity.  At this point our primary example is a comparison between catalysts 4 and 10 (fused cyclohexane compared to two appended phenyl groups).  Catalyst 10 works much better in the two alcohol oxidation reactions (reactions 1 and 3), but yields of the reduction reactions are much more comparable.  We have just started examining the reactivity of compounds 13–16, and we plan on synthesizing and exploring the compounds shown in Figure 2.  Results from reactions catalyzed by these compounds compared to those catalyzed by 6–12 will give us more insight into the impact that substitution at each position of cyclopentadienone has on catalyst reactivity.  

  Impact on Undergraduate Research Program   A total of 12 undergraduate students have worked on this project over the years, and six of those have been directly impacted by the funding provided by the ACS PRF.  Of those six, two are in graduate school, one is employed in the chemical industry, and the remaining three are still undergraduate students.  It has helped provide the resources and the consistency to get this project to the point where we can collect a large amount of data in a relatively short amount of time.  Since receiving funding from the ACS PRF, we have presented our results at both regional and national conferences, including ACS meetings, and we have plans to continue this into the future.