1. Michael R. Hurst, Cassidy L. Kotelman, and Katrina H. Jensen
Black Hills State University
1200 University Street, Spearfish, SD 57799
Katrina.Jensen@bhsu.edu
I. Introduction III. Catalytic Cycle V. Photocatalyst Synthesis
VIII. Future Research
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 to initiate a reaction. We are
working towards developing new reactions using a chiral
catalyst and a photoredox catalyst with the end goal of
synthesizing small molecules.
In photoredox catalysis, light energy is absorbed by a
catalyst, moving the catalyst into an excited state. From this
high energy level, it can then donate or accept an electron
from organic reagents. The resulting molecule is a highly
reactive radical intermediate.
light
Energy
photo-
excitation
Ground State Excited State
oxidation
– e–
Oxidized State
II. Background and Significance
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, nontoxic, and
relatively inexpensive. Furthermore, bisphenanthroline
copper complexes2 are known with similar photophysical
properties as Ru(bpy)3
2+.
Cost per ounce:
Ruthenium: $56.00
Copper: $0.18
Abundance in Earth’s crust:
Ruthenium: 0.000000099%
Copper: 0.0068%
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
In general, photoredox catalysis shows great potential in
many chemical applications due to its low energy
requirement. Instead of relying on the energy of other
mechanical or chemical sources, this reaction methodology
only necessitates the light of a standard lightbulb, reducing
costs and boosting efficiency.
One specific application of photoredox catalysis is in the
synthesis of small molecules, which are being used in the
improvement and utilization of disease treatments.
In the following catalytic cycle, on which we have chosen to
focus,3 both a chiral catalyst and a photocatalyst are involved in
the reaction. These species act together in dual catalytic cycles.
3D. A. Nicewicz, D. W. C. MacMillan Science 2008, 322, 77-80
IV. Chiral Catalyst Synthesis
10% yield62% yield
9% yield 2% yield
We examined photoredox catalysts in Reaction A, shown here:
A chiral catalyst provides facial selectivity in our asymmetric
photoredox reaction. We synthesized our desired chiral
catalyst, 2, in four steps, beginning from molecule 1.
Shown below is the synthesis of 2.
Chiral Catalyst Synthesis4:
4T. H. Graham, B. D. Horning, D. W. C MacMillan, Org. Synth., 2011, 88, 42-53.
VI. Exploring Copper Photocatalysts
A
D
F
BE
C
1H NMR
IX. Acknowledgements
Research team: (back)
(front)
Dr. Katrina Jensen, Michael Hurst, Cassidy Kotelman
Alissa Iverson, Thomas Trimble, and Sarah Souder
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 for support of this research
Photoredox Catalysts:
• Short term goals
- Continue to optimize the reaction conditions,
evaluating factors such as light source, solvent
system, scale, and ratio of each reactant.
- Evaluate the scope of the reaction by evaluating
other aldehyde and α-bromocarbonyl pairs as
reaction partners.
- Determine enantiomeric excess of reaction with
high pressure liquid chromatography (HPLC).
• Long term goals
- Use the developed reaction methodology to target
natural products and other molecules for
synthesis. These would include biologically active
molecules offering medicinal benefits such as
antimicrobial activity.
A photocatalyst interacts with light to catalyze a reaction. We
synthesized a number of a copper complexes with this
property. Shown below is the synthesis of Cu(dap)2Cl.
Photocatalyst Synthesis:
1H NMR
VII. Changing Solvent Systems
Using Cu(dap)2Cl in Reaction A, we tested several solvent
systems in order to improve percent yield.
Solvent Percent Yield
DMF 9%
CH2Cl2 62%
MeCN 10%
DMSO 55%
CHCl3 17%
Toluene 18%
Benzene 24%
THF 19%
EtOAc 29%
Et2O 71%
Dichloroethane 18%
TBME 72%
Chlorobenzene 42%
After identifying CH2Cl2 as
our most viable solvent, we
further altered percent yield
by increasing concentration
of the reactants.
mL CH2Cl2 Percent Yield
0.8 62%
0.6 41%
0.4 45%
0.2 66%
0.0 75%
Percent yields were measured using
gas chromatography with an internal
standard (tetradecane). The percent
yields were evaluated between t=18
and t=22 hours.
Reaction Conditions: 0.800 mL of solvent, 0.800 mmol octaldehyde, 0.400 mmol
diethylbromomalonate, 0.080 mmol chiral catalyst, 0.004 mmol photocatalyst,
0.800 mmol 2,6-lutidine, and 0.080 mmol tetradecane.
Reaction A is prepared
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 B C CD3OD D E F
1H NMR
1 91% yield 95% yield
91% yield 2 48% yield
A B C D E F
A
B
C
D
F
E
+
A CDCl3 B C D E E’ F G
A
B
C
D
F
G
F
In this mechanism, the chiral catalyst works to properly orient
a reactant molecule and to make it more reactive. This allows a
free radical to attach, forming an enantiomer. In photoredox
reactions involving Ru(bpy)3, this free radical is the result of
reductive quenching.
Our research has focused on using Cu(phen’)2 complexes in
place of Ru(bpy)3. We propose that this will yield a free radical
through oxidation, still effectively enabling the overall reaction.