60th Annual Report on Research 2015

Our goal is to develop copper catalysts for photoredox reactions, where visible light is used to facilitate electron transfer reactions.  Light can be considered a reagent in such reactions, which is both economical and environmentally friendly.  While most catalytic photoredox reactions are reported using ruthenium or iridium photocatalysts;[1]  we are interested in developing photocatalysts that use copper, which is much more abundant.  We started our investigation with bis(phenanthroline) copper(I) complexes which are known to have photophysical properties similar to proven photoredox catalyst Ru(bpy)₃Cl₂ (Table 1).[2]

Previous Results

In the first year of this project, we evaluated a series of bis(phenanthroline) copper(I) complexes as catalysts in the photoredox reaction shown in equation 1.  This enantioselective reaction was first reported by MacMillan using Ru(bpy)₃Cl₂ as a photoredox catalyst, and imidazolidinone 1 as a chiral catalyst.[3]  We started our investigation by replacing the ruthenium catalyst with various copper catalysts, and also evaluated multiple solvents. 

Of the copper catalysts we evaluated, Cu(dap)₂Cl (dap = 2,9-di-para-anisole-1,10-phenanthroline, Figure 1) gave the most promising results.  We developed an assay using gas chromatography to quantify reactant conversion and product yield based on comparison to an internal standard (tetradecane).  This assay was intended to expedite screening by eliminating the need to purify and isolate the product after every experiment.  During our initial solvent screen, we observed the highest yields using either dichloromethane (CH₂Cl₂, 66% GC yield) or ethereal solvents (Et₂O, 71% or TBME, 72%).

Current Results

In the second year of this grant, we worked to continue to optimize reaction conditions, measure reaction enantioselectivity, and expand this catalyst system to other types of reactants.  Unfortunately, we started to observe inconsistencies in the results we obtained using the GC assay.  While working to resolve the issue with our GC instrument, we reevaluated our catalytic results using isolated yields (Table 2).  Unfortunately the isolated yields were reduced as compared to the yields determined by GC.

During this time, we also worked to determine the enantioselectivity of these reactions.  The reported procedure³ to determine product enantiomeric ratio involves the derivatization of product 4 with (2S,4S)-pentanediol to form diastereomeric acetals 5 and 6, the ratio of which can be measured with ¹H NMR by comparing the integrations of peaks at 3.70 ppm (d) and 3.66 ppm (d) in the mixture (Scheme 1).  This measurement proved difficult for the product from some of the reactions due to other overlapping peaks in this region, thus the enantiomeric ratio is yet to be determined from certain catalytic reaction conditions.  Black Hills State University (with the support of the South Dakota Biomedical Research Infrastructure Network) was recently able to purchase a new HPLC to use for enantiomeric separations, and we plan to use this instrument equipped with columns containing chiral stationary phases to make all future ER measurements.

We also explored the use of copper photocatalysts in other reactions, including the α-benzylation of aldehydes using electron poor benzyl bromides (Table 3).[4]  The optimal product yield was observed without solvent (entry 6).  We plan to develop methods to separate and measure the enantiomeric ratio of product 8 using the new HPLC discussed above, as well as explore the scope of these reactions.

Impacts

Support from the ACS PRF has provided the opportunity for the PI to grow her research program at BHSU.  This UNI grant has provided support, either directly or indirectly, for ten undergraduate students to be trained in advanced organic synthesis, compound purification, and analytical techniques such as GC, GC/MS, and NMR.  During this reporting period, three students were financially supported partially by PRF during the academic year, as well as two students during the summer.  In addition, one student earned research credit, and three students working on this project, or a closely related project, were supported by summer fellowships (two from the South Dakota Biomedical Research Infrastructure Network and one from a Green and Environmental Chemistry REU).  PRF support has greatly expanded the chemistry research opportunities for undergraduate students at BHSU, especially compared to before the PI joined the faculty.

Undergraduate students working in the PI’s lab presented a total of fifteen posters during this reporting period (12 on photoredox catalysis, 3 on other projects) at local, regional, and national meetings, including the Black Hills Research Symposium, the National Conference on Undergraduate Research, the National Meeting of the American Chemical Society (Denver, CO), the South Dakota EPSCoR Research Symposium, and at the annual meeting of the South Dakota Biomedical Research Infrastructure Network.  In addition, one student gave an oral presentation at the annual meeting of the South Dakota Academy of Science, and the PI gave an oral presentation at the National ACS Meeting in Denver.  Travel to the ACS meeting for the PI and three undergraduate students was partially supported by this grant.