The researchers are developing new copper photocatalysts as more sustainable alternatives to ruthenium complexes commonly used in photoredox reactions. They synthesized copper complexes by first making dichlorinated phenanthroline ligands, then reacting them with copper sources to form homoleptic and heteroleptic complexes. These copper photocatalysts were evaluated in an alkylation reaction and yielded products ranging from 1% to 59%, demonstrating their potential as replacements for ruthenium complexes which are toxic, rare, and expensive.

1. Michael R. Hurst, Thomas G. Trimble, Cassidy L. Kotelman, Wesley A. Deutscher, and Katrina H. Jensen
Black Hills State University
1200 University Blvd, Spearfish, SD 57799
Katrina.Jensen@bhsu.edu
Evaluation of Copper Photocatalysts in the Enantioselective α–Alkylation of Aldehydes
Catalysts act to increase the rate of reactions by lowering the
activation energy required. We are working to develop new
reactions using a chiral catalyst and a photoredox catalyst with the
goal of developing effective and efficient methods to synthesize
small molecules.
In reactions utilizing photoredox catalysis, light energy is absorbed
by a catalyst, moving the catalyst into an excited state. From this
high energy level, it can donate or accept an electron from organic
reagents.
light
Energy
photo-
excitation
Ground State Excited State
oxidation
– e–
Oxidized State
In our research, we are attempting to develop copper catalysts
for photoredox reactions. Currently, reported photoredox
reactions1 use ruthenium and iridium complexes; however,
copper would make for a more sustainable alternative as it is
earth-abundant, and relatively inexpensive. Furthermore,
bisphenanthroline copper complexes2 are known with similar
photophysical properties to Ru(bpy)3
2+.
1J. W. Tucker, C. R. J. Stephenson J. Org. Chem. 2012, 77, 1617-1622
2D. V. Scaltrito, D. W. Thompson, J. A. O’Callaghan, G. J. Meyer Coord. Chem. Rev. 2000,
208, 243-266
Photoredox catalysis shows great potential in chemical synthesis
due to the inherent reactivity of the free radical intermediates
that can be selectively accessed. Instead of relying on specialized
photochemical equipment, this reaction methodology only
necessitates the light of a standard light bulb, reducing costs and
boosting efficiency.
This dichlorinated 1,10-phenanthroline derivative is then reacted
with a number of possible substituents to yield a given ligand.
Shown here is the theoretical synthesis of (dap):
Research reported in this publication was supported by an
Institutional Development Award (IDeA) from the National
Institute of General Medical Sciences of the National Institutes of
Health under grant number P20GM103443. The content is solely
the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
Acknowledgement is also made to the donors of the American
Chemical Society Petroleum Research Fund, the South Dakota
Biomedical Research Infrastructure Network, and Black Hills
State University for support of this research.
• Short-term goals
- Continue optimizing the reaction conditions to
improve product yield and enantiomeric excess,
evaluating factors such as light source, solvent
system, scale, and the ratio of reactants.
- Evaluate the scope of the alkylation reaction by
evaluating other aldehyde and α-bromocarbonyl pairs
as reaction partners.
- Utilize NMR assay to study product formation.
• Long-term goal
- Use the developed reaction methodology to target
natural products and other significant molecules for
synthesis. These would include biologically-active
compounds offering medicinal benefits such as
antimicrobial activity.
1H NMR
Reaction Conditions: 0.800 mL of solvent, 0.800 mmol octaldehyde, 0.400 mmol
diethylbromomalonate, 0.080 mmol chiral catalyst, 0.004 mmol photocatalyst, and
0.800 mmol 2,6-lutidine.
Reaction A is setup by
mixing a standard solution
with our photo catalyst
and chiral catalyst, then
placing mixture within 3
cm of a 26 watt light
source for ~18 hours.
A CHCl3 B C D E E’ F G
A
B
C
D
F
G
F
VI. Evaluating Photocatalysts
Reaction A:
In the alkylation reaction3 both chiral catalyst and photocatalyst
are required. These species act together in dual catalytic cycles.
3D. A. Nicewicz, D. W. C. MacMillan Science 2008, 322, 77-80
In this mechanism, a chiral catalyst reacts with an aldehyde to
properly orient it and improve its reactivity by forming an
enamine. This intermediate reacts with the free radical
intermediate formed during a photoredox reaction involving
Ru(bpy)3 and selectively forms a new carbon-carbon bond.
Our research has focused on using derivatives of copper(I)
bisphenanthroline complexes (Cu(phen’)2
+) in place of Ru(bpy)3.
# Time Area Area %
1 5.786 12.6 17.655
2 6.203 58.8 82.345
# Time Area Area %
1 5.889 120.4 50.423
2 6.352 118.4 49.577
A racemic form of our product was used as a
standard against which enantiomerically-
enriched products are evaluated.
Enantiomeric excess = 65%
This reaction was set up to the specifications
outlined in panel III.
To determine the enantiomeric excess of our products, an HPLC
assay was developed. The assay was run with 95:5 hexanes:IPA
through an Agilent Technologies 1260 Infinity series HPLC
loaded with an CHIRALPAK® AS-H column.
The first step in producing copper complex photocatalysts is ligand
synthesis. Ligands are synthesized by first forming a dichlorinated
1,10-phenathroline derivative, as shown4:
We examined photoredox catalysts in Reaction A shown below:
These ligands can then be formed into copper complexes via a
reaction with a copper source. Shown is the synthesis of
Cu(BINAP)(dap), a heteroleptic copper complex:
4J. Frey, T. Kraus, V. Heitz, J.P. Sauvage Chem. Eur. J. 2007, 13, 7584-7594
The complexes synthesized as described above were then
evaluated by measuring the alkylation product yield in Reaction A.
V. Photocatalyst SynthesisIII. Alkylation ReactionI. Introduction VII. Enantiomeric Excess
IV. Catalytic Cycle
II. Background and Significance
VIII. Future Research
IX. Acknowledgements
Heteroleptic:
Homoleptic:
Yield: 16% Yield: 59% Yield: 1%
Yield: 45% Yield: 37% Yield: 12% Yield: 11%
Cost per ounce
Ruthenium: $42.00
Copper: $0.14
Abundance in Earth’s Crust
Ruthenium: 0.000000099%
Copper: 0.0068%
Toxicity
Ruthenium: considered toxic and carcinogenic
Copper: considered moderately non-toxic
74%
37%
79%
76%
Left-to-right: Katrina Jensen, Hannah Owen, Michael Hurst,
Madison Jilek, Wesley Deutscher, Cheyloh Bluemel, Thomas Trimble
Left:
Ru(bpy)3Cl2 • 6H2O
Right:
Cu(BINAP)(dap)BF4